Will Pass

AMSTERDAM – Rozanolixizumab, a subcutaneous antibody for the human neonatal Fc receptor, provides clinically meaningful improvements in platelet count for patients with primary immune thrombocytopenia, according to results from a recent phase 2 trial.

Rozanolixizumab was well tolerated across all dose groups, with higher doses delivering faster responses, reported lead author Tadeusz Robak, MD, PhD, of the Medical University of Lodz (Poland).

Targeting the Fc receptor interrupts recirculation of IgG, a key autoantibody in immune thrombocytopenia (ITP) pathogenesis, Dr. Robak explained during a presentation at the annual congress of the European Hematology Association. This approach represents an emerging treatment paradigm, he said, noting that rozanolixizumab is also being studied for the treatment of other IgG-driven autoimmune diseases, such as myasthenia gravis and chronic inflammatory demyelinating polyneuropathy.

The present open-label, dose-escalation study involved 54 adult patients with primary ITP of at least 3 months duration and platelet counts of less than 30 x 10⁹/L at screening and 35 x 10⁹/L at baseline. Eligibility required a previous response to ITP therapy. Enrolled patients were randomized into four dose groups: 4 mg/kg (five doses), 7 mg/kg (three doses), 10 mg/kg (two doses), or 15 mg/kg (one dose). After dosing, patients were followed for 8 weeks. Clinically relevant efficacy was defined as a platelet count of at least 50 x 10⁹/L. Decreases in IgG were also reported.

A safety analysis showed that the regimen was well tolerated across all dose groups. In total, 20.4% of patients experienced at least one treatment-related adverse event. The most common adverse events were headache (31.5%), diarrhea (11.1%), and vomiting (3.7%); all of which were mild or moderate. Headache appeared to be dose related, as 42% of patients in the 15-mg/kg group reported headache, compared with 8% in the 10-mg/kg group, 7% in the 7-mg/kg group, and none in the 4-mg/kg group. Out of four reported serious adverse events, none were considered treatment related.

Concerning efficacy, higher doses were associated with higher response rates and faster response times. In the 4-mg/kg group, 33% of patients achieved a platelet count of at least 50 x 10⁹/L, compared with 33% of the 7-mg/kg group, 50% of the 10-mg/kg group, and 67% of the 15-mg/kg group. Of the patients that achieved clinically meaningful responses, 20% of the 4-mg/kg group did so within 8 days, compared with 40% of 7-mg/kg responders, 50% of 10-mg/kg responders, and 87.5% of 15-mg/kg responders. Additional observations included dose-dependent decreases in IgG titer and longer response durations after multiple lower doses.

“Data from this study indicate that we can achieve effective increases in platelet levels, we can observe decreasing IgG levels, and the treatment was safe for the patients,” Dr. Robak said.

When asked about the intended clinical application of rozanolixizumab, Dr. Robak suggested that the agent may have a role in the postacute care setting. “We should develop a method of prolonged administration of [rozanolixizumab], as we saw that lower, multiple doses gave longer response durations.”

Still, he noted that more research is needed, since responses in diverse patient populations remain unknown. “We do not know how the drug will be active in truly refractory patients and we need this response before we establish the indication for the drug.”

The investigators reported financial relationships with Celgene, Roche, GlaxoSmithKline, Amgen, AbbVie, and other companies.

SOURCE: Robak T et al. EHA Congress, Abstract S850.

AMSTERDAM – Rozanolixizumab, a subcutaneous antibody for the human neonatal Fc receptor, provides clinically meaningful improvements in platelet count for patients with primary immune thrombocytopenia, according to results from a recent phase 2 trial.

Rozanolixizumab was well tolerated across all dose groups, with higher doses delivering faster responses, reported lead author Tadeusz Robak, MD, PhD, of the Medical University of Lodz (Poland).

Targeting the Fc receptor interrupts recirculation of IgG, a key autoantibody in immune thrombocytopenia (ITP) pathogenesis, Dr. Robak explained during a presentation at the annual congress of the European Hematology Association. This approach represents an emerging treatment paradigm, he said, noting that rozanolixizumab is also being studied for the treatment of other IgG-driven autoimmune diseases, such as myasthenia gravis and chronic inflammatory demyelinating polyneuropathy.

The present open-label, dose-escalation study involved 54 adult patients with primary ITP of at least 3 months duration and platelet counts of less than 30 x 10⁹/L at screening and 35 x 10⁹/L at baseline. Eligibility required a previous response to ITP therapy. Enrolled patients were randomized into four dose groups: 4 mg/kg (five doses), 7 mg/kg (three doses), 10 mg/kg (two doses), or 15 mg/kg (one dose). After dosing, patients were followed for 8 weeks. Clinically relevant efficacy was defined as a platelet count of at least 50 x 10⁹/L. Decreases in IgG were also reported.

A safety analysis showed that the regimen was well tolerated across all dose groups. In total, 20.4% of patients experienced at least one treatment-related adverse event. The most common adverse events were headache (31.5%), diarrhea (11.1%), and vomiting (3.7%); all of which were mild or moderate. Headache appeared to be dose related, as 42% of patients in the 15-mg/kg group reported headache, compared with 8% in the 10-mg/kg group, 7% in the 7-mg/kg group, and none in the 4-mg/kg group. Out of four reported serious adverse events, none were considered treatment related.

Concerning efficacy, higher doses were associated with higher response rates and faster response times. In the 4-mg/kg group, 33% of patients achieved a platelet count of at least 50 x 10⁹/L, compared with 33% of the 7-mg/kg group, 50% of the 10-mg/kg group, and 67% of the 15-mg/kg group. Of the patients that achieved clinically meaningful responses, 20% of the 4-mg/kg group did so within 8 days, compared with 40% of 7-mg/kg responders, 50% of 10-mg/kg responders, and 87.5% of 15-mg/kg responders. Additional observations included dose-dependent decreases in IgG titer and longer response durations after multiple lower doses.

“Data from this study indicate that we can achieve effective increases in platelet levels, we can observe decreasing IgG levels, and the treatment was safe for the patients,” Dr. Robak said.

When asked about the intended clinical application of rozanolixizumab, Dr. Robak suggested that the agent may have a role in the postacute care setting. “We should develop a method of prolonged administration of [rozanolixizumab], as we saw that lower, multiple doses gave longer response durations.”

Still, he noted that more research is needed, since responses in diverse patient populations remain unknown. “We do not know how the drug will be active in truly refractory patients and we need this response before we establish the indication for the drug.”

The investigators reported financial relationships with Celgene, Roche, GlaxoSmithKline, Amgen, AbbVie, and other companies.

SOURCE: Robak T et al. EHA Congress, Abstract S850.

AMSTERDAM – Rozanolixizumab, a subcutaneous antibody for the human neonatal Fc receptor, provides clinically meaningful improvements in platelet count for patients with primary immune thrombocytopenia, according to results from a recent phase 2 trial.

Rozanolixizumab was well tolerated across all dose groups, with higher doses delivering faster responses, reported lead author Tadeusz Robak, MD, PhD, of the Medical University of Lodz (Poland).

Targeting the Fc receptor interrupts recirculation of IgG, a key autoantibody in immune thrombocytopenia (ITP) pathogenesis, Dr. Robak explained during a presentation at the annual congress of the European Hematology Association. This approach represents an emerging treatment paradigm, he said, noting that rozanolixizumab is also being studied for the treatment of other IgG-driven autoimmune diseases, such as myasthenia gravis and chronic inflammatory demyelinating polyneuropathy.

The present open-label, dose-escalation study involved 54 adult patients with primary ITP of at least 3 months duration and platelet counts of less than 30 x 10⁹/L at screening and 35 x 10⁹/L at baseline. Eligibility required a previous response to ITP therapy. Enrolled patients were randomized into four dose groups: 4 mg/kg (five doses), 7 mg/kg (three doses), 10 mg/kg (two doses), or 15 mg/kg (one dose). After dosing, patients were followed for 8 weeks. Clinically relevant efficacy was defined as a platelet count of at least 50 x 10⁹/L. Decreases in IgG were also reported.

A safety analysis showed that the regimen was well tolerated across all dose groups. In total, 20.4% of patients experienced at least one treatment-related adverse event. The most common adverse events were headache (31.5%), diarrhea (11.1%), and vomiting (3.7%); all of which were mild or moderate. Headache appeared to be dose related, as 42% of patients in the 15-mg/kg group reported headache, compared with 8% in the 10-mg/kg group, 7% in the 7-mg/kg group, and none in the 4-mg/kg group. Out of four reported serious adverse events, none were considered treatment related.

Concerning efficacy, higher doses were associated with higher response rates and faster response times. In the 4-mg/kg group, 33% of patients achieved a platelet count of at least 50 x 10⁹/L, compared with 33% of the 7-mg/kg group, 50% of the 10-mg/kg group, and 67% of the 15-mg/kg group. Of the patients that achieved clinically meaningful responses, 20% of the 4-mg/kg group did so within 8 days, compared with 40% of 7-mg/kg responders, 50% of 10-mg/kg responders, and 87.5% of 15-mg/kg responders. Additional observations included dose-dependent decreases in IgG titer and longer response durations after multiple lower doses.

“Data from this study indicate that we can achieve effective increases in platelet levels, we can observe decreasing IgG levels, and the treatment was safe for the patients,” Dr. Robak said.

When asked about the intended clinical application of rozanolixizumab, Dr. Robak suggested that the agent may have a role in the postacute care setting. “We should develop a method of prolonged administration of [rozanolixizumab], as we saw that lower, multiple doses gave longer response durations.”

Still, he noted that more research is needed, since responses in diverse patient populations remain unknown. “We do not know how the drug will be active in truly refractory patients and we need this response before we establish the indication for the drug.”

The investigators reported financial relationships with Celgene, Roche, GlaxoSmithKline, Amgen, AbbVie, and other companies.

SOURCE: Robak T et al. EHA Congress, Abstract S850.

AMSTERDAM – For patients with immune thrombocytopenia (ITP), platelet glycoprotein genotypes may predict effectiveness of specific therapies, according to investigators.

Will Pass/MDedge News

Significant relationships were detected between allelic polymorphisms of glycoprotein genes and durable responses to corticosteroids, thrombopoietin receptor agonists (aTPOr), and splenectomy, reported lead author Irina Zotova, MD, of the Russian Research Institute of Hematology and Transfusiology, Federal Biomedical Agency, in Saint Petersburg and colleagues.

These findings could guide clinical decision making in ITP, according to Dr. Zotova.

“Currently, the choice of therapeutic approach to ITP treatment, especially the second-line, is empirical, and often based on the experience of the clinician,” Dr. Zotova said during her presentation at the annual congress of the European Hematology Association. “Recent studies have shown that ... genes coding for glycoprotein are involved in platelet function and are associated with different responses to ITP treatment. This provides an opportunity for an individual approach and personalization of ITP therapy in accordance with the genetic status of the patient.”

In the present study, the investigators used PCR-RFLP (polymerase chain reaction–restriction fragment length polymorphism) to determine GPIa A1648G and GPIIb 2622TG gene status in 81 patients with primary ITP and compared these genotypes with clinical responses.

All patients received first-line corticosteroid therapy. If necessary, second-line treatment was delivered. In total, 37 patients (46%) received aTPOr, while 22 patients (27%) underwent splenectomy. Responses were classified as durable response, nondurable response, or no response.

Analysis showed that a significantly greater proportion of patients who had durable responses to corticosteroid therapy exhibited a heterozygous GPIIb 2622TG genotype, compared with patients who had nondurable responses (72.2% vs. 30.9%; odds ratio, 5.8; P = .005).

For second-line responses, patients who had durable response to aTPOr were much more likely to be homozygous for the GPIa A1648G than nonresponders (87.5% vs. 20.0%; OR, 28.0; P = .005). More strikingly, all patients who achieved durable responses to splenectomy had the GPIa A1648G genotype, compared with just 44% of nonresponders (OR, 33.0; P = .005).

“Gentoyping for the GPIIb T2622G and GPIa A1648G polymorphisms allows [clinicians] to predict the response to first-line and second-line treatment, giving the possibility to stratify patients to groups with favorable and unfavorable courses of the disease,” Dr. Zotova concluded.

Will Pass/MDedge News

Session moderator János Kappelmayer, MD, of the University of Debrecen (Hungary) highlighted a key opportunity presented by the study. “I think that one important aspect of these findings could be that splenectomy is an irreversible procedure, so one can exclude those patients who will not benefit from splenectomy,” he said. “I think this is a real advantage.”

The investigators reported no study funding or conflicts of interest.

SOURCE: Zotova I et al. EHA Congress, Abstract S848.

AMSTERDAM – For patients with immune thrombocytopenia (ITP), platelet glycoprotein genotypes may predict effectiveness of specific therapies, according to investigators.

Will Pass/MDedge News

Significant relationships were detected between allelic polymorphisms of glycoprotein genes and durable responses to corticosteroids, thrombopoietin receptor agonists (aTPOr), and splenectomy, reported lead author Irina Zotova, MD, of the Russian Research Institute of Hematology and Transfusiology, Federal Biomedical Agency, in Saint Petersburg and colleagues.

These findings could guide clinical decision making in ITP, according to Dr. Zotova.

“Currently, the choice of therapeutic approach to ITP treatment, especially the second-line, is empirical, and often based on the experience of the clinician,” Dr. Zotova said during her presentation at the annual congress of the European Hematology Association. “Recent studies have shown that ... genes coding for glycoprotein are involved in platelet function and are associated with different responses to ITP treatment. This provides an opportunity for an individual approach and personalization of ITP therapy in accordance with the genetic status of the patient.”

In the present study, the investigators used PCR-RFLP (polymerase chain reaction–restriction fragment length polymorphism) to determine GPIa A1648G and GPIIb 2622TG gene status in 81 patients with primary ITP and compared these genotypes with clinical responses.

All patients received first-line corticosteroid therapy. If necessary, second-line treatment was delivered. In total, 37 patients (46%) received aTPOr, while 22 patients (27%) underwent splenectomy. Responses were classified as durable response, nondurable response, or no response.

Analysis showed that a significantly greater proportion of patients who had durable responses to corticosteroid therapy exhibited a heterozygous GPIIb 2622TG genotype, compared with patients who had nondurable responses (72.2% vs. 30.9%; odds ratio, 5.8; P = .005).

For second-line responses, patients who had durable response to aTPOr were much more likely to be homozygous for the GPIa A1648G than nonresponders (87.5% vs. 20.0%; OR, 28.0; P = .005). More strikingly, all patients who achieved durable responses to splenectomy had the GPIa A1648G genotype, compared with just 44% of nonresponders (OR, 33.0; P = .005).

“Gentoyping for the GPIIb T2622G and GPIa A1648G polymorphisms allows [clinicians] to predict the response to first-line and second-line treatment, giving the possibility to stratify patients to groups with favorable and unfavorable courses of the disease,” Dr. Zotova concluded.

Will Pass/MDedge News

Session moderator János Kappelmayer, MD, of the University of Debrecen (Hungary) highlighted a key opportunity presented by the study. “I think that one important aspect of these findings could be that splenectomy is an irreversible procedure, so one can exclude those patients who will not benefit from splenectomy,” he said. “I think this is a real advantage.”

The investigators reported no study funding or conflicts of interest.

SOURCE: Zotova I et al. EHA Congress, Abstract S848.

AMSTERDAM – For patients with immune thrombocytopenia (ITP), platelet glycoprotein genotypes may predict effectiveness of specific therapies, according to investigators.

Will Pass/MDedge News

Significant relationships were detected between allelic polymorphisms of glycoprotein genes and durable responses to corticosteroids, thrombopoietin receptor agonists (aTPOr), and splenectomy, reported lead author Irina Zotova, MD, of the Russian Research Institute of Hematology and Transfusiology, Federal Biomedical Agency, in Saint Petersburg and colleagues.

These findings could guide clinical decision making in ITP, according to Dr. Zotova.

“Currently, the choice of therapeutic approach to ITP treatment, especially the second-line, is empirical, and often based on the experience of the clinician,” Dr. Zotova said during her presentation at the annual congress of the European Hematology Association. “Recent studies have shown that ... genes coding for glycoprotein are involved in platelet function and are associated with different responses to ITP treatment. This provides an opportunity for an individual approach and personalization of ITP therapy in accordance with the genetic status of the patient.”

In the present study, the investigators used PCR-RFLP (polymerase chain reaction–restriction fragment length polymorphism) to determine GPIa A1648G and GPIIb 2622TG gene status in 81 patients with primary ITP and compared these genotypes with clinical responses.

All patients received first-line corticosteroid therapy. If necessary, second-line treatment was delivered. In total, 37 patients (46%) received aTPOr, while 22 patients (27%) underwent splenectomy. Responses were classified as durable response, nondurable response, or no response.

Analysis showed that a significantly greater proportion of patients who had durable responses to corticosteroid therapy exhibited a heterozygous GPIIb 2622TG genotype, compared with patients who had nondurable responses (72.2% vs. 30.9%; odds ratio, 5.8; P = .005).

For second-line responses, patients who had durable response to aTPOr were much more likely to be homozygous for the GPIa A1648G than nonresponders (87.5% vs. 20.0%; OR, 28.0; P = .005). More strikingly, all patients who achieved durable responses to splenectomy had the GPIa A1648G genotype, compared with just 44% of nonresponders (OR, 33.0; P = .005).

“Gentoyping for the GPIIb T2622G and GPIa A1648G polymorphisms allows [clinicians] to predict the response to first-line and second-line treatment, giving the possibility to stratify patients to groups with favorable and unfavorable courses of the disease,” Dr. Zotova concluded.

Will Pass/MDedge News

Session moderator János Kappelmayer, MD, of the University of Debrecen (Hungary) highlighted a key opportunity presented by the study. “I think that one important aspect of these findings could be that splenectomy is an irreversible procedure, so one can exclude those patients who will not benefit from splenectomy,” he said. “I think this is a real advantage.”

The investigators reported no study funding or conflicts of interest.

SOURCE: Zotova I et al. EHA Congress, Abstract S848.

Amsterdam – For patients with untreated mantle cell lymphoma (MCL), the anti-CD20 monoclonal antibody obinutuzumab may one day offer an alternative to rituximab, according to investigators.

Patients in the LYMA-101 trial were given four cycles of obinutuzumab in combination with dexamethasone, high-dose aracytine, and platinum chemotherapy (O-DHAP), followed by autologous stem cell transplantation (ASCT) and maintenance obinutuzumab. After a median follow-up of 14.6 months, ranging from 3.8 to 24.4 months, 85% of evaluable patients had achieved minimal residual disease (MRD) in bone marrow, reported lead author Steven Le Gouill, MD, PhD, of the University Hospital of Nantes, and his colleagues.

In this disease population, an MRD rate of 85% is “unprecedented,” Dr. Le Gouill said during his presentation at the annual congress of the European Hematology Association. Based on findings from LYMA-101 and preclinical data, Dr. Le Gouill suggested that obinutuzumab may become an alternative to rituximab, the current standard anti-CD20 antibody.

“There are few data of interest for obinutuzumab in MCL, but there is a strong rationale in the lab as obinutuzumab has a different mechanism of action against tumor cells [than rituximab], with more efficacy against MCL cells,” Dr. Le Gouill said.

Data from the ongoing phase 2 trial were drawn from 85 patients with untreated MCL who were 65 years or younger at the time of enrollment. More specifically, median patient age was 55.5 years and 17.4% of patients had blastoid disease. All patients were given the O-DHAP/ASCT/obinutuzumab protocol, with a maintenance period of 3 years. Thereafter, MRD-positive patients may receive obinutuzumab on-demand.

The primary endpoint was MRD in bone marrow after induction therapy, measured by quantitative PCR (qPCR) and droplet digital PCR (ddPCR). Secondary endpoints included response rates, survival measures, incidence of stem cell collection failure after O-DHAP, and MRD rates at additional therapeutic time points.

Owing to the ongoing nature of the study, Dr. Le Gouill focused on the primary endpoint during his presentation.

Analysis showed that 75% and 85% of evaluable patients had achieved negative MRD in bone marrow after induction, according to qPCR and ddPCR, respectively.

These early findings give “a flavor of the results in terms of efficacy,” Dr. Le Gouill said, noting that “the median follow-up is pretty short.”

Still, 1-year findings were “very promising,” he said, with a progression-free survival of 93.4% and overall survival of 96%.

Twelve patients stopped treatment before ASCT, three prior to maintenance, and nine during maintenance. Of these 24 patients, 13 stopped treatment because of adverse events. The remaining 11 patients halted therapy because of disease progression, other malignancies, or death.

From the original 85 patients, 3 patients died and 3 progressed. Considering all of these findings, and that no major toxicities were encountered, the investigators concluded that the regimen was safe.

Overall, the results suggest that further research is needed, Dr. Le Gouill concluded. “Maybe this is where obinutuzumab may have stronger efficacy in MCL, as compared to rituximab,” he said.

The study is sponsored by the Lymphoma Academic Research Organisation. The investigators reported relationships with Roche, Janssen-Cilag, Gilead, Servier, and Novartis.

SOURCE: Le Gouill S et al. EHA Congress, Abstract S103.

Amsterdam – For patients with untreated mantle cell lymphoma (MCL), the anti-CD20 monoclonal antibody obinutuzumab may one day offer an alternative to rituximab, according to investigators.

Patients in the LYMA-101 trial were given four cycles of obinutuzumab in combination with dexamethasone, high-dose aracytine, and platinum chemotherapy (O-DHAP), followed by autologous stem cell transplantation (ASCT) and maintenance obinutuzumab. After a median follow-up of 14.6 months, ranging from 3.8 to 24.4 months, 85% of evaluable patients had achieved minimal residual disease (MRD) in bone marrow, reported lead author Steven Le Gouill, MD, PhD, of the University Hospital of Nantes, and his colleagues.

In this disease population, an MRD rate of 85% is “unprecedented,” Dr. Le Gouill said during his presentation at the annual congress of the European Hematology Association. Based on findings from LYMA-101 and preclinical data, Dr. Le Gouill suggested that obinutuzumab may become an alternative to rituximab, the current standard anti-CD20 antibody.

“There are few data of interest for obinutuzumab in MCL, but there is a strong rationale in the lab as obinutuzumab has a different mechanism of action against tumor cells [than rituximab], with more efficacy against MCL cells,” Dr. Le Gouill said.

Data from the ongoing phase 2 trial were drawn from 85 patients with untreated MCL who were 65 years or younger at the time of enrollment. More specifically, median patient age was 55.5 years and 17.4% of patients had blastoid disease. All patients were given the O-DHAP/ASCT/obinutuzumab protocol, with a maintenance period of 3 years. Thereafter, MRD-positive patients may receive obinutuzumab on-demand.

The primary endpoint was MRD in bone marrow after induction therapy, measured by quantitative PCR (qPCR) and droplet digital PCR (ddPCR). Secondary endpoints included response rates, survival measures, incidence of stem cell collection failure after O-DHAP, and MRD rates at additional therapeutic time points.

Owing to the ongoing nature of the study, Dr. Le Gouill focused on the primary endpoint during his presentation.

Analysis showed that 75% and 85% of evaluable patients had achieved negative MRD in bone marrow after induction, according to qPCR and ddPCR, respectively.

These early findings give “a flavor of the results in terms of efficacy,” Dr. Le Gouill said, noting that “the median follow-up is pretty short.”

Still, 1-year findings were “very promising,” he said, with a progression-free survival of 93.4% and overall survival of 96%.

Twelve patients stopped treatment before ASCT, three prior to maintenance, and nine during maintenance. Of these 24 patients, 13 stopped treatment because of adverse events. The remaining 11 patients halted therapy because of disease progression, other malignancies, or death.

From the original 85 patients, 3 patients died and 3 progressed. Considering all of these findings, and that no major toxicities were encountered, the investigators concluded that the regimen was safe.

Overall, the results suggest that further research is needed, Dr. Le Gouill concluded. “Maybe this is where obinutuzumab may have stronger efficacy in MCL, as compared to rituximab,” he said.

The study is sponsored by the Lymphoma Academic Research Organisation. The investigators reported relationships with Roche, Janssen-Cilag, Gilead, Servier, and Novartis.

SOURCE: Le Gouill S et al. EHA Congress, Abstract S103.

Amsterdam – For patients with untreated mantle cell lymphoma (MCL), the anti-CD20 monoclonal antibody obinutuzumab may one day offer an alternative to rituximab, according to investigators.

Patients in the LYMA-101 trial were given four cycles of obinutuzumab in combination with dexamethasone, high-dose aracytine, and platinum chemotherapy (O-DHAP), followed by autologous stem cell transplantation (ASCT) and maintenance obinutuzumab. After a median follow-up of 14.6 months, ranging from 3.8 to 24.4 months, 85% of evaluable patients had achieved minimal residual disease (MRD) in bone marrow, reported lead author Steven Le Gouill, MD, PhD, of the University Hospital of Nantes, and his colleagues.

In this disease population, an MRD rate of 85% is “unprecedented,” Dr. Le Gouill said during his presentation at the annual congress of the European Hematology Association. Based on findings from LYMA-101 and preclinical data, Dr. Le Gouill suggested that obinutuzumab may become an alternative to rituximab, the current standard anti-CD20 antibody.

“There are few data of interest for obinutuzumab in MCL, but there is a strong rationale in the lab as obinutuzumab has a different mechanism of action against tumor cells [than rituximab], with more efficacy against MCL cells,” Dr. Le Gouill said.

Data from the ongoing phase 2 trial were drawn from 85 patients with untreated MCL who were 65 years or younger at the time of enrollment. More specifically, median patient age was 55.5 years and 17.4% of patients had blastoid disease. All patients were given the O-DHAP/ASCT/obinutuzumab protocol, with a maintenance period of 3 years. Thereafter, MRD-positive patients may receive obinutuzumab on-demand.

The primary endpoint was MRD in bone marrow after induction therapy, measured by quantitative PCR (qPCR) and droplet digital PCR (ddPCR). Secondary endpoints included response rates, survival measures, incidence of stem cell collection failure after O-DHAP, and MRD rates at additional therapeutic time points.

Owing to the ongoing nature of the study, Dr. Le Gouill focused on the primary endpoint during his presentation.

Analysis showed that 75% and 85% of evaluable patients had achieved negative MRD in bone marrow after induction, according to qPCR and ddPCR, respectively.

These early findings give “a flavor of the results in terms of efficacy,” Dr. Le Gouill said, noting that “the median follow-up is pretty short.”

Still, 1-year findings were “very promising,” he said, with a progression-free survival of 93.4% and overall survival of 96%.

Twelve patients stopped treatment before ASCT, three prior to maintenance, and nine during maintenance. Of these 24 patients, 13 stopped treatment because of adverse events. The remaining 11 patients halted therapy because of disease progression, other malignancies, or death.

From the original 85 patients, 3 patients died and 3 progressed. Considering all of these findings, and that no major toxicities were encountered, the investigators concluded that the regimen was safe.

Overall, the results suggest that further research is needed, Dr. Le Gouill concluded. “Maybe this is where obinutuzumab may have stronger efficacy in MCL, as compared to rituximab,” he said.

The study is sponsored by the Lymphoma Academic Research Organisation. The investigators reported relationships with Roche, Janssen-Cilag, Gilead, Servier, and Novartis.

SOURCE: Le Gouill S et al. EHA Congress, Abstract S103.

For patients with advanced cirrhosis and acute variceal bleeding, early treatment with transjugular intrahepatic portosystemic shunt (TIPS) appears to improve transplantation-free survival, according to investigators.

Early TIPS “should therefore be preferred to the current standard of care,” reported lead author Yong Lv, MD, of the Fourth Military Medical University in Xi’an, China, and colleagues, referring to standard pharmaceutical and endoscopic therapy.

“[The current standard] approach has improved patient outcomes,” the investigators wrote in the Lancet Gastroenterology & Hepatology. “However, up to 10%-20% of patients still experience treatment failure, requiring further intensive management. In such patients, [TIPS] is successful in achieving hemostasis in 90%-100% of patients. However, 6-week mortality remains high [35%-55%]. This is probably because the severity of the underlying liver disease has worsened and additional organ dysfunction may have occurred after several failed endoscopic therapy attempts.”

Previous studies have explored earlier intervention with TIPS; however, according to the investigators, these trials were inconclusive for various reasons. For example, uncovered stents and an out-of-date control therapy were employed in a trial by Monescillo et al., while a study by Garcia-Pagan et al. lacked a primary survival endpoint and has been criticized for selection bias. “Thus, whether early TIPS confers a survival benefit in a broader population remains to be assessed,” the investigators wrote.

To this end, the investigators screened 373 patients with advanced cirrhosis (Child-Pugh class B or C) and acute variceal bleeding. Of these, 132 were eligible for inclusion based on age, disease severity, willingness to participate, comorbidities, and other factors. Patients were randomized 2:1 to receive either early TIPS or standard therapy. Within 12 hours of hospital admission for the initial bleeding episode, all patients received vasoactive drugs or endoscopic band ligation and prophylactic antibiotics. Control patients continued vasoactive drugs for up to 5 days, followed by propranolol, which was titrated to reduce resting heart rate by 25% but not less than 55 beats per minute. Elective endoscopic band ligation was performed within 1-2 weeks of initial endoscopic treatment, then approximately every 2 weeks until variceal eradication, and additionally if varices reappeared. TIPS was allowed as rescue therapy. In contrast, patients in the TIPS group underwent the procedure with conscious sedation and local anesthesia within 72 hours of diagnostic endoscopy, followed by approximately 1 week of antibiotics and vasoactive drugs. TIPS revision with angioplasty or another stent placement was performed in the event of shunt dysfunction or reemergence of portal hypertensive complications. The final dataset contained 127 patients, as 3 were excluded after randomization because of exclusionary diagnoses, 1 withdrew consent, and 1 died before TIPS placement.

The primary endpoint was transplantation-free survival. The secondary endpoints were new or worsening ascites based on ultrasound score or sustained ascites necessitating paracentesis, failure to control bleeding or rebleeding, overt hepatic encephalopathy, other complications of portal hypertension, and adverse events.

After a median follow-up of 24 months, data analysis showed a survival benefit associated with early TIPS based on multiple measures. Out of 84 patients in the TIPS group, 15 (18%) died during follow-up, compared with 15 (33%) in the control group. Actuarial transplantation-free survival was also better with TIPS instead of standard therapy at 6 weeks (99% vs. 84%), 1 year (86% vs. 73%), and 2 years (79% vs. 64%). The hazard ratio for transplantation-free survival was 0.50 in favor of TIPS (P = .04). These survival advantages were maintained regardless of hepatitis B virus status or Child-Pugh/Model for End-Stage Liver Disease score.

Similarly to transplantation-free survival, patients treated with TIPS were more likely to be free of uncontrolled bleeding or rebleeding at 1 year (89% vs. 66%) and 2 years (86% vs. 57%). The associated hazard ratio for this outcome favored early TIPS (HR, 0.26; P less than .0001), and univariate and multivariate analysis confirmed an independent protective role. In further support of superiority over standard therapy, patients treated with TIPS were more likely than those in the control group to be free of new or worsening ascites at 1 year (89% vs. 57%) and 2 years (81% vs. 54%).

No significant intergroup differences were found for rates of overt hepatic encephalopathy, hepatic hydrothorax, hepatorenal syndrome, spontaneous bacterial peritonitis, hepatocellular carcinoma, serious adverse events, or nonserious adverse events. At 1 and 3 months, patients in the TIPS group had a slight increase of median bilirubin concentrations and median international normalized ratio; however, these values normalized after 6 months. A similar temporal pattern was observed in early TIPS patients with regard to median Model for End-Stage Liver Disease score.

“[The transplantation-free survival benefit of early TIPS] was probably related to better control of factors contributing to death, such as failure to control bleeding or rebleeding or new or worsening ascites, without increasing the frequency and severity of overt hepatic encephalopathy and other adverse events,” the investigators concluded. “This study provides direct evidence and greater confidence in the recommendations of current guidelines that early TIPS should be performed in high-risk patients without contraindications.

“Future studies addressing whether early TIPS can be equally recommended in Child-Pugh B and C patients are warranted,” the investigators added.

The study was funded by the National Key Technology R&D Program, Boost Program of Xijing Hospital, Optimized Overall Project of Shaanxi Province, and National Natural Science Foundation of China. The investigators reported no conflicts of interest.

SOURCE: Lv Y et al. Lancet Gastroenterol Hepatol. 2019 May 29. doi: 10.1016/S2468-1253(19)30090-1.

For patients with advanced cirrhosis and acute variceal bleeding, early treatment with transjugular intrahepatic portosystemic shunt (TIPS) appears to improve transplantation-free survival, according to investigators.

Early TIPS “should therefore be preferred to the current standard of care,” reported lead author Yong Lv, MD, of the Fourth Military Medical University in Xi’an, China, and colleagues, referring to standard pharmaceutical and endoscopic therapy.

“[The current standard] approach has improved patient outcomes,” the investigators wrote in the Lancet Gastroenterology & Hepatology. “However, up to 10%-20% of patients still experience treatment failure, requiring further intensive management. In such patients, [TIPS] is successful in achieving hemostasis in 90%-100% of patients. However, 6-week mortality remains high [35%-55%]. This is probably because the severity of the underlying liver disease has worsened and additional organ dysfunction may have occurred after several failed endoscopic therapy attempts.”

Previous studies have explored earlier intervention with TIPS; however, according to the investigators, these trials were inconclusive for various reasons. For example, uncovered stents and an out-of-date control therapy were employed in a trial by Monescillo et al., while a study by Garcia-Pagan et al. lacked a primary survival endpoint and has been criticized for selection bias. “Thus, whether early TIPS confers a survival benefit in a broader population remains to be assessed,” the investigators wrote.

To this end, the investigators screened 373 patients with advanced cirrhosis (Child-Pugh class B or C) and acute variceal bleeding. Of these, 132 were eligible for inclusion based on age, disease severity, willingness to participate, comorbidities, and other factors. Patients were randomized 2:1 to receive either early TIPS or standard therapy. Within 12 hours of hospital admission for the initial bleeding episode, all patients received vasoactive drugs or endoscopic band ligation and prophylactic antibiotics. Control patients continued vasoactive drugs for up to 5 days, followed by propranolol, which was titrated to reduce resting heart rate by 25% but not less than 55 beats per minute. Elective endoscopic band ligation was performed within 1-2 weeks of initial endoscopic treatment, then approximately every 2 weeks until variceal eradication, and additionally if varices reappeared. TIPS was allowed as rescue therapy. In contrast, patients in the TIPS group underwent the procedure with conscious sedation and local anesthesia within 72 hours of diagnostic endoscopy, followed by approximately 1 week of antibiotics and vasoactive drugs. TIPS revision with angioplasty or another stent placement was performed in the event of shunt dysfunction or reemergence of portal hypertensive complications. The final dataset contained 127 patients, as 3 were excluded after randomization because of exclusionary diagnoses, 1 withdrew consent, and 1 died before TIPS placement.

The primary endpoint was transplantation-free survival. The secondary endpoints were new or worsening ascites based on ultrasound score or sustained ascites necessitating paracentesis, failure to control bleeding or rebleeding, overt hepatic encephalopathy, other complications of portal hypertension, and adverse events.

After a median follow-up of 24 months, data analysis showed a survival benefit associated with early TIPS based on multiple measures. Out of 84 patients in the TIPS group, 15 (18%) died during follow-up, compared with 15 (33%) in the control group. Actuarial transplantation-free survival was also better with TIPS instead of standard therapy at 6 weeks (99% vs. 84%), 1 year (86% vs. 73%), and 2 years (79% vs. 64%). The hazard ratio for transplantation-free survival was 0.50 in favor of TIPS (P = .04). These survival advantages were maintained regardless of hepatitis B virus status or Child-Pugh/Model for End-Stage Liver Disease score.

Similarly to transplantation-free survival, patients treated with TIPS were more likely to be free of uncontrolled bleeding or rebleeding at 1 year (89% vs. 66%) and 2 years (86% vs. 57%). The associated hazard ratio for this outcome favored early TIPS (HR, 0.26; P less than .0001), and univariate and multivariate analysis confirmed an independent protective role. In further support of superiority over standard therapy, patients treated with TIPS were more likely than those in the control group to be free of new or worsening ascites at 1 year (89% vs. 57%) and 2 years (81% vs. 54%).

No significant intergroup differences were found for rates of overt hepatic encephalopathy, hepatic hydrothorax, hepatorenal syndrome, spontaneous bacterial peritonitis, hepatocellular carcinoma, serious adverse events, or nonserious adverse events. At 1 and 3 months, patients in the TIPS group had a slight increase of median bilirubin concentrations and median international normalized ratio; however, these values normalized after 6 months. A similar temporal pattern was observed in early TIPS patients with regard to median Model for End-Stage Liver Disease score.

“[The transplantation-free survival benefit of early TIPS] was probably related to better control of factors contributing to death, such as failure to control bleeding or rebleeding or new or worsening ascites, without increasing the frequency and severity of overt hepatic encephalopathy and other adverse events,” the investigators concluded. “This study provides direct evidence and greater confidence in the recommendations of current guidelines that early TIPS should be performed in high-risk patients without contraindications.

“Future studies addressing whether early TIPS can be equally recommended in Child-Pugh B and C patients are warranted,” the investigators added.

The study was funded by the National Key Technology R&D Program, Boost Program of Xijing Hospital, Optimized Overall Project of Shaanxi Province, and National Natural Science Foundation of China. The investigators reported no conflicts of interest.

SOURCE: Lv Y et al. Lancet Gastroenterol Hepatol. 2019 May 29. doi: 10.1016/S2468-1253(19)30090-1.

For patients with advanced cirrhosis and acute variceal bleeding, early treatment with transjugular intrahepatic portosystemic shunt (TIPS) appears to improve transplantation-free survival, according to investigators.

Early TIPS “should therefore be preferred to the current standard of care,” reported lead author Yong Lv, MD, of the Fourth Military Medical University in Xi’an, China, and colleagues, referring to standard pharmaceutical and endoscopic therapy.

“[The current standard] approach has improved patient outcomes,” the investigators wrote in the Lancet Gastroenterology & Hepatology. “However, up to 10%-20% of patients still experience treatment failure, requiring further intensive management. In such patients, [TIPS] is successful in achieving hemostasis in 90%-100% of patients. However, 6-week mortality remains high [35%-55%]. This is probably because the severity of the underlying liver disease has worsened and additional organ dysfunction may have occurred after several failed endoscopic therapy attempts.”

Previous studies have explored earlier intervention with TIPS; however, according to the investigators, these trials were inconclusive for various reasons. For example, uncovered stents and an out-of-date control therapy were employed in a trial by Monescillo et al., while a study by Garcia-Pagan et al. lacked a primary survival endpoint and has been criticized for selection bias. “Thus, whether early TIPS confers a survival benefit in a broader population remains to be assessed,” the investigators wrote.

To this end, the investigators screened 373 patients with advanced cirrhosis (Child-Pugh class B or C) and acute variceal bleeding. Of these, 132 were eligible for inclusion based on age, disease severity, willingness to participate, comorbidities, and other factors. Patients were randomized 2:1 to receive either early TIPS or standard therapy. Within 12 hours of hospital admission for the initial bleeding episode, all patients received vasoactive drugs or endoscopic band ligation and prophylactic antibiotics. Control patients continued vasoactive drugs for up to 5 days, followed by propranolol, which was titrated to reduce resting heart rate by 25% but not less than 55 beats per minute. Elective endoscopic band ligation was performed within 1-2 weeks of initial endoscopic treatment, then approximately every 2 weeks until variceal eradication, and additionally if varices reappeared. TIPS was allowed as rescue therapy. In contrast, patients in the TIPS group underwent the procedure with conscious sedation and local anesthesia within 72 hours of diagnostic endoscopy, followed by approximately 1 week of antibiotics and vasoactive drugs. TIPS revision with angioplasty or another stent placement was performed in the event of shunt dysfunction or reemergence of portal hypertensive complications. The final dataset contained 127 patients, as 3 were excluded after randomization because of exclusionary diagnoses, 1 withdrew consent, and 1 died before TIPS placement.

The primary endpoint was transplantation-free survival. The secondary endpoints were new or worsening ascites based on ultrasound score or sustained ascites necessitating paracentesis, failure to control bleeding or rebleeding, overt hepatic encephalopathy, other complications of portal hypertension, and adverse events.

After a median follow-up of 24 months, data analysis showed a survival benefit associated with early TIPS based on multiple measures. Out of 84 patients in the TIPS group, 15 (18%) died during follow-up, compared with 15 (33%) in the control group. Actuarial transplantation-free survival was also better with TIPS instead of standard therapy at 6 weeks (99% vs. 84%), 1 year (86% vs. 73%), and 2 years (79% vs. 64%). The hazard ratio for transplantation-free survival was 0.50 in favor of TIPS (P = .04). These survival advantages were maintained regardless of hepatitis B virus status or Child-Pugh/Model for End-Stage Liver Disease score.

Similarly to transplantation-free survival, patients treated with TIPS were more likely to be free of uncontrolled bleeding or rebleeding at 1 year (89% vs. 66%) and 2 years (86% vs. 57%). The associated hazard ratio for this outcome favored early TIPS (HR, 0.26; P less than .0001), and univariate and multivariate analysis confirmed an independent protective role. In further support of superiority over standard therapy, patients treated with TIPS were more likely than those in the control group to be free of new or worsening ascites at 1 year (89% vs. 57%) and 2 years (81% vs. 54%).

No significant intergroup differences were found for rates of overt hepatic encephalopathy, hepatic hydrothorax, hepatorenal syndrome, spontaneous bacterial peritonitis, hepatocellular carcinoma, serious adverse events, or nonserious adverse events. At 1 and 3 months, patients in the TIPS group had a slight increase of median bilirubin concentrations and median international normalized ratio; however, these values normalized after 6 months. A similar temporal pattern was observed in early TIPS patients with regard to median Model for End-Stage Liver Disease score.

“[The transplantation-free survival benefit of early TIPS] was probably related to better control of factors contributing to death, such as failure to control bleeding or rebleeding or new or worsening ascites, without increasing the frequency and severity of overt hepatic encephalopathy and other adverse events,” the investigators concluded. “This study provides direct evidence and greater confidence in the recommendations of current guidelines that early TIPS should be performed in high-risk patients without contraindications.

“Future studies addressing whether early TIPS can be equally recommended in Child-Pugh B and C patients are warranted,” the investigators added.

The study was funded by the National Key Technology R&D Program, Boost Program of Xijing Hospital, Optimized Overall Project of Shaanxi Province, and National Natural Science Foundation of China. The investigators reported no conflicts of interest.

SOURCE: Lv Y et al. Lancet Gastroenterol Hepatol. 2019 May 29. doi: 10.1016/S2468-1253(19)30090-1.

A blueprint for the future of augmented intelligence (AuI) in dermatology – including a definition of high-quality AuI, steps in the development of AuI models and integration into clinical settings, and postmarketing surveillance – is the focus of a newly published American Academy of Dermatology (AAD) position statement.

The statement describes AuI as “a concept that focuses on artificial intelligence’s (AI) assistive role,” emphasizing that AuI is “designed to enhance human intelligence and the physician/patient relationship,” not to replace that relationship. The statement, available on the AAD website, also emphasizes the importance of the human-centered nature of this concept as dermatologists integrate AuI into their practice, noting that “patients should feel well cared for even when interacting with software.”

“We are at the precipice of seeing the beginnings of augmented intelligence tools influence our practice,” statement coauthor Justin M. Ko, MD, MBA, said in an interview. “At the outset, it will likely be systems and tools that are working on practice management processes, insights, and analytics. However, I don’t believe we’re far from seeing the mainstream integration say, of triage, point of care diagnostic support, or chronic disease management capabilities that rely in some part on augmented intelligence models.”

“The key is that we recognize that this is on the horizon, and that we actively work to shape the development and deployment of these tools in a responsible way that enhances patient care and ensures that patient safety is held paramount,” added Dr. Ko, director and chief of medical dermatology at Stanford (Calif.) University.

“We want patients and clinicians to recognize the potential of such tools to augment the core care relationship and improve the delivery of such care,” he explained. “At the same time, we know that, from the technology that exists all around us in all aspects of our lives, that despite the best intentions, there [may be] unintended consequences in the medical realm. We must be cognizant of possibilities, for example, of amplifying bias and increasing health inequity, and take an active approach to mitigating these risks.”

The AAD position statement notes that high-quality AuI will be “designed and evaluated in a manner that enables the delivery of high-quality care to patients.” During development and clinical deployment, the statement highlighted the importance of collaboration with practitioners, and that “AuI must integrate into physician and provider workflows.” The statement advises that AuI tools should be regulated appropriately, and that postmarketing surveillance will be necessary after clinical launch of these tools, measuring outcomes such as “quality, cost, and/or efficiency of care delivery.”

While the first half of the statement provides a roadmap for AuI development and implementation, the second half further emphasizes collaboration and communication with a number of stakeholders. “Effective and ethical development and implementation of AuI will require continuous engagement, education, exploration of privacy and medical-legal issues, and advocacy,” the statement says. “Although the promise of AuI to improve health and wellness holds significant potential,” the statement says, “issues related to privacy and medical-legal complications are amplified by technology that requires transmission of data beyond the confines of a providers’ institution. Protected Health Information must be managed with effective safeguards to prevent inadvertent exposure.”

The conclusion of the statement revisits the game-changing nature of AuI while asserting the AAD’s commitment to guiding integration with dermatology practice. “AuI has the potential to transform our collective and personal experience of health, health care, and wellness,” the AAD wrote. “To achieve this potential, deliberate and diligent efforts must be taken to engage and collaborate with stakeholders and policy makers. The Academy hopes to work with administrative and legislative colleagues to create policies that promote AuI that is high quality, inclusive, equitable, and accessible. Through collaboration and research, the Academy strives to guide the design, implementation, and regulation of these technologies and augment care for all.”

The statement also includes a glossary of terms used in this area. The AAD’s Ad Hoc Taskforce on Augmented Intelligence wrote the position statement; Dr. Ko is on the task force and serves as its chairman.

A blueprint for the future of augmented intelligence (AuI) in dermatology – including a definition of high-quality AuI, steps in the development of AuI models and integration into clinical settings, and postmarketing surveillance – is the focus of a newly published American Academy of Dermatology (AAD) position statement.

The statement describes AuI as “a concept that focuses on artificial intelligence’s (AI) assistive role,” emphasizing that AuI is “designed to enhance human intelligence and the physician/patient relationship,” not to replace that relationship. The statement, available on the AAD website, also emphasizes the importance of the human-centered nature of this concept as dermatologists integrate AuI into their practice, noting that “patients should feel well cared for even when interacting with software.”

“We are at the precipice of seeing the beginnings of augmented intelligence tools influence our practice,” statement coauthor Justin M. Ko, MD, MBA, said in an interview. “At the outset, it will likely be systems and tools that are working on practice management processes, insights, and analytics. However, I don’t believe we’re far from seeing the mainstream integration say, of triage, point of care diagnostic support, or chronic disease management capabilities that rely in some part on augmented intelligence models.”

“The key is that we recognize that this is on the horizon, and that we actively work to shape the development and deployment of these tools in a responsible way that enhances patient care and ensures that patient safety is held paramount,” added Dr. Ko, director and chief of medical dermatology at Stanford (Calif.) University.

“We want patients and clinicians to recognize the potential of such tools to augment the core care relationship and improve the delivery of such care,” he explained. “At the same time, we know that, from the technology that exists all around us in all aspects of our lives, that despite the best intentions, there [may be] unintended consequences in the medical realm. We must be cognizant of possibilities, for example, of amplifying bias and increasing health inequity, and take an active approach to mitigating these risks.”

The AAD position statement notes that high-quality AuI will be “designed and evaluated in a manner that enables the delivery of high-quality care to patients.” During development and clinical deployment, the statement highlighted the importance of collaboration with practitioners, and that “AuI must integrate into physician and provider workflows.” The statement advises that AuI tools should be regulated appropriately, and that postmarketing surveillance will be necessary after clinical launch of these tools, measuring outcomes such as “quality, cost, and/or efficiency of care delivery.”

While the first half of the statement provides a roadmap for AuI development and implementation, the second half further emphasizes collaboration and communication with a number of stakeholders. “Effective and ethical development and implementation of AuI will require continuous engagement, education, exploration of privacy and medical-legal issues, and advocacy,” the statement says. “Although the promise of AuI to improve health and wellness holds significant potential,” the statement says, “issues related to privacy and medical-legal complications are amplified by technology that requires transmission of data beyond the confines of a providers’ institution. Protected Health Information must be managed with effective safeguards to prevent inadvertent exposure.”

The conclusion of the statement revisits the game-changing nature of AuI while asserting the AAD’s commitment to guiding integration with dermatology practice. “AuI has the potential to transform our collective and personal experience of health, health care, and wellness,” the AAD wrote. “To achieve this potential, deliberate and diligent efforts must be taken to engage and collaborate with stakeholders and policy makers. The Academy hopes to work with administrative and legislative colleagues to create policies that promote AuI that is high quality, inclusive, equitable, and accessible. Through collaboration and research, the Academy strives to guide the design, implementation, and regulation of these technologies and augment care for all.”

The statement also includes a glossary of terms used in this area. The AAD’s Ad Hoc Taskforce on Augmented Intelligence wrote the position statement; Dr. Ko is on the task force and serves as its chairman.

A blueprint for the future of augmented intelligence (AuI) in dermatology – including a definition of high-quality AuI, steps in the development of AuI models and integration into clinical settings, and postmarketing surveillance – is the focus of a newly published American Academy of Dermatology (AAD) position statement.

The statement describes AuI as “a concept that focuses on artificial intelligence’s (AI) assistive role,” emphasizing that AuI is “designed to enhance human intelligence and the physician/patient relationship,” not to replace that relationship. The statement, available on the AAD website, also emphasizes the importance of the human-centered nature of this concept as dermatologists integrate AuI into their practice, noting that “patients should feel well cared for even when interacting with software.”

“We are at the precipice of seeing the beginnings of augmented intelligence tools influence our practice,” statement coauthor Justin M. Ko, MD, MBA, said in an interview. “At the outset, it will likely be systems and tools that are working on practice management processes, insights, and analytics. However, I don’t believe we’re far from seeing the mainstream integration say, of triage, point of care diagnostic support, or chronic disease management capabilities that rely in some part on augmented intelligence models.”

“The key is that we recognize that this is on the horizon, and that we actively work to shape the development and deployment of these tools in a responsible way that enhances patient care and ensures that patient safety is held paramount,” added Dr. Ko, director and chief of medical dermatology at Stanford (Calif.) University.

“We want patients and clinicians to recognize the potential of such tools to augment the core care relationship and improve the delivery of such care,” he explained. “At the same time, we know that, from the technology that exists all around us in all aspects of our lives, that despite the best intentions, there [may be] unintended consequences in the medical realm. We must be cognizant of possibilities, for example, of amplifying bias and increasing health inequity, and take an active approach to mitigating these risks.”

The AAD position statement notes that high-quality AuI will be “designed and evaluated in a manner that enables the delivery of high-quality care to patients.” During development and clinical deployment, the statement highlighted the importance of collaboration with practitioners, and that “AuI must integrate into physician and provider workflows.” The statement advises that AuI tools should be regulated appropriately, and that postmarketing surveillance will be necessary after clinical launch of these tools, measuring outcomes such as “quality, cost, and/or efficiency of care delivery.”

While the first half of the statement provides a roadmap for AuI development and implementation, the second half further emphasizes collaboration and communication with a number of stakeholders. “Effective and ethical development and implementation of AuI will require continuous engagement, education, exploration of privacy and medical-legal issues, and advocacy,” the statement says. “Although the promise of AuI to improve health and wellness holds significant potential,” the statement says, “issues related to privacy and medical-legal complications are amplified by technology that requires transmission of data beyond the confines of a providers’ institution. Protected Health Information must be managed with effective safeguards to prevent inadvertent exposure.”

The conclusion of the statement revisits the game-changing nature of AuI while asserting the AAD’s commitment to guiding integration with dermatology practice. “AuI has the potential to transform our collective and personal experience of health, health care, and wellness,” the AAD wrote. “To achieve this potential, deliberate and diligent efforts must be taken to engage and collaborate with stakeholders and policy makers. The Academy hopes to work with administrative and legislative colleagues to create policies that promote AuI that is high quality, inclusive, equitable, and accessible. Through collaboration and research, the Academy strives to guide the design, implementation, and regulation of these technologies and augment care for all.”

The statement also includes a glossary of terms used in this area. The AAD’s Ad Hoc Taskforce on Augmented Intelligence wrote the position statement; Dr. Ko is on the task force and serves as its chairman.

A combination of venetoclax and ibrutinib may be a safe and effective treatment option for previously untreated elderly and high-risk patients with chronic lymphocytic leukemia (CLL), according to investigators of a phase 2 trial of the combination.

VashiDonsk/Wikimedia Commons/Creative Commons BY-SA 3.0

About 88% of patients achieved complete remission or complete remission with incomplete count recovery after 12 cycles of treatment, reported lead author Nitin Jain, MD, of the University of Texas MD Anderson Cancer Center, Houston, and colleagues.

There were no new safety signals for the combination of ibrutinib, an irreversible inhibitor of Bruton’s tyrosine kinase, and venetoclax, a B-cell lymphoma 2 protein inhibitor, the investigators noted.

“This combination was reported to be safe and active in patients with mantle cell lymphoma,” they wrote in the New England Journal of Medicine. “Given the clinically complementary activity, preclinical synergism, and nonoverlapping toxic effects, we examined the safety and efficacy of combined ibrutinib and venetoclax treatment in previously untreated patients with CLL.”

In particular, the investigators recruited older patients, as this is a common population that can be challenging to treat. “Because CLL typically occurs in older adults, the majority of patients who need treatment are older than 65 years of age,” the investigators wrote. “This group of patients often has unacceptable side effects and has a lower rate of complete remission and undetectable minimal residual disease with chemoimmunotherapy than younger patients.”

The open-label, phase 2 trial enrolled 80 elderly and high-risk patients with previously untreated CLL. Eligibility required an age of at least 65 years or presence of at least one high-risk genetic feature; namely, mutated TP53, unmutated IgVH, or chromosome 11q deletion.

In order to reduce the risk of tumor lysis syndrome, ibrutinib (420 mg once daily) was given as monotherapy for three 28-day cycles. From the fourth cycle onward, venetoclax was also given, with weekly dose escalations to a target dose of 400 mg once daily. The combination was given for 24 cycles, with treatment continuation offered to patients who were still positive for minimal residual disease.

The median patient age was 65 years, with 30% of the population aged 70 years or older. A large majority (92%) had at least one high-risk genetic feature.

Following initiation with three cycles of ibrutinib, most patients had partial responses, the investigators wrote; however, with the addition of venetoclax, responses improved over time. Of all 80 patients, 59 (74%) had a best response of complete remission or complete remission with incomplete count recovery.

After six cycles, 51 out of 70 patients (73%) achieved this marker. After 12 cycles, 29 of 33 patients (88%) had this response, with 61% of the same group demonstrating undetectable minimal residual disease in bone marrow.

After 18 cycles, 25 of 26 patients (96%) had complete remission or complete remission with incomplete count recovery, 18 of which (69%) were negative for minimal residual disease. Three patients completed 24 cycles of combined therapy, all of whom achieved complete remission or complete remission with incomplete count recovery and undetectable minimal residual disease.

Focusing on patients aged 65 years or older, 74% had complete remission or complete remission with incomplete count recovery after six cycles of therapy and nearly half (44%) had undetectable minimal residual disease. After 12 cycles, these rates increased to 94% and 76%, respectively. Responses were also seen across genetically high-risk subgroups.

One patient died from a cryptococcal infection of the central nervous system; this was deemed unrelated to treatment, as symptoms began prior to initiation of treatment and only one dose of ibrutinib was given.

The estimated 1-year progression-free survival rate was 98% and the estimated overall survival rate was 99%. At the time of publication, no patients had disease progression.

Among all patients, 60% experienced grade 3 or higher adverse events, the most common being neutropenia (48%).

Almost half of the patient population (44%) required dose reductions of ibrutinib, most commonly because of atrial fibrillation, and 24% required dose reductions of venetoclax, most often because of neutropenia.

“Our data showed that combination therapy with ibrutinib and venetoclax was effective in patients with CLL, with no new toxic effects from the combination that were not reported previously for the individual agents,” the investigators wrote, adding that the efficacy findings were also “substantially better” than what has been reported with monotherapy for each of the agents in patients with CLL.

The study was funded by AbbVie, the University of Texas MD Anderson Cancer Center Chronic Lymphocytic Leukemia Moon Shot program, the Andrew Sabin Family Foundation, and the CLL Global Research Foundation. The investigators reported relationships with AbbVie, Incyte, Celgene, and other companies.

SOURCE: Jain N et al. N Engl J Med. 2019;380:2095-103.

A combination of venetoclax and ibrutinib may be a safe and effective treatment option for previously untreated elderly and high-risk patients with chronic lymphocytic leukemia (CLL), according to investigators of a phase 2 trial of the combination.

VashiDonsk/Wikimedia Commons/Creative Commons BY-SA 3.0

About 88% of patients achieved complete remission or complete remission with incomplete count recovery after 12 cycles of treatment, reported lead author Nitin Jain, MD, of the University of Texas MD Anderson Cancer Center, Houston, and colleagues.

There were no new safety signals for the combination of ibrutinib, an irreversible inhibitor of Bruton’s tyrosine kinase, and venetoclax, a B-cell lymphoma 2 protein inhibitor, the investigators noted.

“This combination was reported to be safe and active in patients with mantle cell lymphoma,” they wrote in the New England Journal of Medicine. “Given the clinically complementary activity, preclinical synergism, and nonoverlapping toxic effects, we examined the safety and efficacy of combined ibrutinib and venetoclax treatment in previously untreated patients with CLL.”

In particular, the investigators recruited older patients, as this is a common population that can be challenging to treat. “Because CLL typically occurs in older adults, the majority of patients who need treatment are older than 65 years of age,” the investigators wrote. “This group of patients often has unacceptable side effects and has a lower rate of complete remission and undetectable minimal residual disease with chemoimmunotherapy than younger patients.”

The open-label, phase 2 trial enrolled 80 elderly and high-risk patients with previously untreated CLL. Eligibility required an age of at least 65 years or presence of at least one high-risk genetic feature; namely, mutated TP53, unmutated IgVH, or chromosome 11q deletion.

In order to reduce the risk of tumor lysis syndrome, ibrutinib (420 mg once daily) was given as monotherapy for three 28-day cycles. From the fourth cycle onward, venetoclax was also given, with weekly dose escalations to a target dose of 400 mg once daily. The combination was given for 24 cycles, with treatment continuation offered to patients who were still positive for minimal residual disease.

The median patient age was 65 years, with 30% of the population aged 70 years or older. A large majority (92%) had at least one high-risk genetic feature.

Following initiation with three cycles of ibrutinib, most patients had partial responses, the investigators wrote; however, with the addition of venetoclax, responses improved over time. Of all 80 patients, 59 (74%) had a best response of complete remission or complete remission with incomplete count recovery.

After six cycles, 51 out of 70 patients (73%) achieved this marker. After 12 cycles, 29 of 33 patients (88%) had this response, with 61% of the same group demonstrating undetectable minimal residual disease in bone marrow.

After 18 cycles, 25 of 26 patients (96%) had complete remission or complete remission with incomplete count recovery, 18 of which (69%) were negative for minimal residual disease. Three patients completed 24 cycles of combined therapy, all of whom achieved complete remission or complete remission with incomplete count recovery and undetectable minimal residual disease.

Focusing on patients aged 65 years or older, 74% had complete remission or complete remission with incomplete count recovery after six cycles of therapy and nearly half (44%) had undetectable minimal residual disease. After 12 cycles, these rates increased to 94% and 76%, respectively. Responses were also seen across genetically high-risk subgroups.

One patient died from a cryptococcal infection of the central nervous system; this was deemed unrelated to treatment, as symptoms began prior to initiation of treatment and only one dose of ibrutinib was given.

The estimated 1-year progression-free survival rate was 98% and the estimated overall survival rate was 99%. At the time of publication, no patients had disease progression.

Among all patients, 60% experienced grade 3 or higher adverse events, the most common being neutropenia (48%).

Almost half of the patient population (44%) required dose reductions of ibrutinib, most commonly because of atrial fibrillation, and 24% required dose reductions of venetoclax, most often because of neutropenia.

“Our data showed that combination therapy with ibrutinib and venetoclax was effective in patients with CLL, with no new toxic effects from the combination that were not reported previously for the individual agents,” the investigators wrote, adding that the efficacy findings were also “substantially better” than what has been reported with monotherapy for each of the agents in patients with CLL.

The study was funded by AbbVie, the University of Texas MD Anderson Cancer Center Chronic Lymphocytic Leukemia Moon Shot program, the Andrew Sabin Family Foundation, and the CLL Global Research Foundation. The investigators reported relationships with AbbVie, Incyte, Celgene, and other companies.

SOURCE: Jain N et al. N Engl J Med. 2019;380:2095-103.

A combination of venetoclax and ibrutinib may be a safe and effective treatment option for previously untreated elderly and high-risk patients with chronic lymphocytic leukemia (CLL), according to investigators of a phase 2 trial of the combination.

VashiDonsk/Wikimedia Commons/Creative Commons BY-SA 3.0

About 88% of patients achieved complete remission or complete remission with incomplete count recovery after 12 cycles of treatment, reported lead author Nitin Jain, MD, of the University of Texas MD Anderson Cancer Center, Houston, and colleagues.

There were no new safety signals for the combination of ibrutinib, an irreversible inhibitor of Bruton’s tyrosine kinase, and venetoclax, a B-cell lymphoma 2 protein inhibitor, the investigators noted.

“This combination was reported to be safe and active in patients with mantle cell lymphoma,” they wrote in the New England Journal of Medicine. “Given the clinically complementary activity, preclinical synergism, and nonoverlapping toxic effects, we examined the safety and efficacy of combined ibrutinib and venetoclax treatment in previously untreated patients with CLL.”

In particular, the investigators recruited older patients, as this is a common population that can be challenging to treat. “Because CLL typically occurs in older adults, the majority of patients who need treatment are older than 65 years of age,” the investigators wrote. “This group of patients often has unacceptable side effects and has a lower rate of complete remission and undetectable minimal residual disease with chemoimmunotherapy than younger patients.”

The open-label, phase 2 trial enrolled 80 elderly and high-risk patients with previously untreated CLL. Eligibility required an age of at least 65 years or presence of at least one high-risk genetic feature; namely, mutated TP53, unmutated IgVH, or chromosome 11q deletion.

In order to reduce the risk of tumor lysis syndrome, ibrutinib (420 mg once daily) was given as monotherapy for three 28-day cycles. From the fourth cycle onward, venetoclax was also given, with weekly dose escalations to a target dose of 400 mg once daily. The combination was given for 24 cycles, with treatment continuation offered to patients who were still positive for minimal residual disease.

The median patient age was 65 years, with 30% of the population aged 70 years or older. A large majority (92%) had at least one high-risk genetic feature.

Following initiation with three cycles of ibrutinib, most patients had partial responses, the investigators wrote; however, with the addition of venetoclax, responses improved over time. Of all 80 patients, 59 (74%) had a best response of complete remission or complete remission with incomplete count recovery.

After six cycles, 51 out of 70 patients (73%) achieved this marker. After 12 cycles, 29 of 33 patients (88%) had this response, with 61% of the same group demonstrating undetectable minimal residual disease in bone marrow.

After 18 cycles, 25 of 26 patients (96%) had complete remission or complete remission with incomplete count recovery, 18 of which (69%) were negative for minimal residual disease. Three patients completed 24 cycles of combined therapy, all of whom achieved complete remission or complete remission with incomplete count recovery and undetectable minimal residual disease.

Focusing on patients aged 65 years or older, 74% had complete remission or complete remission with incomplete count recovery after six cycles of therapy and nearly half (44%) had undetectable minimal residual disease. After 12 cycles, these rates increased to 94% and 76%, respectively. Responses were also seen across genetically high-risk subgroups.

One patient died from a cryptococcal infection of the central nervous system; this was deemed unrelated to treatment, as symptoms began prior to initiation of treatment and only one dose of ibrutinib was given.

The estimated 1-year progression-free survival rate was 98% and the estimated overall survival rate was 99%. At the time of publication, no patients had disease progression.

Among all patients, 60% experienced grade 3 or higher adverse events, the most common being neutropenia (48%).

Almost half of the patient population (44%) required dose reductions of ibrutinib, most commonly because of atrial fibrillation, and 24% required dose reductions of venetoclax, most often because of neutropenia.

“Our data showed that combination therapy with ibrutinib and venetoclax was effective in patients with CLL, with no new toxic effects from the combination that were not reported previously for the individual agents,” the investigators wrote, adding that the efficacy findings were also “substantially better” than what has been reported with monotherapy for each of the agents in patients with CLL.

The study was funded by AbbVie, the University of Texas MD Anderson Cancer Center Chronic Lymphocytic Leukemia Moon Shot program, the Andrew Sabin Family Foundation, and the CLL Global Research Foundation. The investigators reported relationships with AbbVie, Incyte, Celgene, and other companies.

SOURCE: Jain N et al. N Engl J Med. 2019;380:2095-103.

For patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplantation (ASCT), adding daratumumab to lenalidomide and dexamethasone provides better outcomes than standard therapy alone, based on an interim analysis from the phase 3 MAIA trial.

A greater proportion of patients in the daratumumab group had complete responses and were alive without disease progression after a median follow-up of 28 months, reported lead author Thierry Facon, MD, of the University of Lille (France) and colleagues, who also noted that daratumumab was associated with higher rates of grade 3 or 4 pneumonia, neutropenia, and lymphopenia.

“For patients who are ineligible for stem-cell transplantation, multiagent regimens, including alkylating agents, glucocorticoids, immunomodulatory drugs, proteasome inhibitors, and new agents, are the standard of care,” the investigators wrote in the New England Journal of Medicine.

The findings from MAIA add clarity to the efficacy and safety of daratumumab in this setting, building on previous phase 3 myeloma trials in the same area, such as ALCYONE, CASTOR, and POLLUX, the investigators noted.

MAIA was an open-label, international trial involving 737 patients with newly diagnosed multiple myeloma who were ineligible for ASCT. Patients were randomized in a 1:1 ratio to receive either daratumumab, lenalidomide, and dexamethasone (daratumumab group; n = 368) or lenalidomide and dexamethasone alone (control group; n = 369).

On a 28-day cycle, all patients received oral lenalidomide 25 mg on days 1-21 and oral dexamethasone 40 mg on days 1, 8, 15, and 22. Patients in the daratumumab group received intravenous daratumumab dosed at 16 mg/kg once a week for cycles 1 and 2, every 2 weeks for cycles 3-6, and then every 4 weeks thereafter. Treatment was continued until unacceptable toxic effects or disease progression occurred.

The primary end point was progression-free survival (PFS). Various secondary end points were also evaluated, including time to progression, complete responses, overall survival, and others.

Among the 737 randomized patients, 729 ultimately underwent treatment. The median patient age was 73 years.

Generally, efficacy measures favored adding daratumumab. After a median follow-up of 28.0 months, disease progression or death had occurred in 26.4% of patients in the daratumumab group, compared with 38.8% in the control group.

The median PFS was not reached in the daratumumab group, compared with 31.9 months in the control group. There was a 44% lower risk of disease progression or death among patients who received daratumumab, compared with the control group (hazard ratio, 0.56, P less than .001).

This PFS trend was consistent across most subgroups, including those for sex, age, and race, with the exception of patients with baseline hepatic impairment.

Additional efficacy measures added weight to the apparent benefit of adding daratumumab. For instance, more patients in the daratumumab group achieved a complete response or better (47.6% vs. 24.9%) and were negative for minimum residual disease (24.2% vs. 7.3%).

In terms of safety, more patients in the daratumumab group than the control group developed grade 3 or higher neutropenia (50% vs. 35.3%), lymphopenia (15.1% vs. 10.7%), infections (32.1% vs. 23.3%) or pneumonia (13.7% vs. 7.9%).

In contrast, grade 3 or 4 anemia was less common in the daratumumab group than the control group (11.8% vs. 19.7%). Overall, the rate of serious adverse events was similar for both groups (approximately 63%), as was the rate of adverse events resulting in death (approximately 6%-7%).

“In this trial involving patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation, the addition of daratumumab to lenalidomide and dexamethasone resulted in significantly longer progression-free survival, a higher response rate, an increased depth of response, and a longer duration of response than lenalidomide and dexamethasone alone,” the investigators concluded.

The study was funded by Janssen Research and Development. The investigators reported relationships with Janssen, Celgene, Takeda, Sanofi, and other companies.

SOURCE: Facon T et al. N Engl J Med. 2019;380:2104-15.

For patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplantation (ASCT), adding daratumumab to lenalidomide and dexamethasone provides better outcomes than standard therapy alone, based on an interim analysis from the phase 3 MAIA trial.

A greater proportion of patients in the daratumumab group had complete responses and were alive without disease progression after a median follow-up of 28 months, reported lead author Thierry Facon, MD, of the University of Lille (France) and colleagues, who also noted that daratumumab was associated with higher rates of grade 3 or 4 pneumonia, neutropenia, and lymphopenia.

“For patients who are ineligible for stem-cell transplantation, multiagent regimens, including alkylating agents, glucocorticoids, immunomodulatory drugs, proteasome inhibitors, and new agents, are the standard of care,” the investigators wrote in the New England Journal of Medicine.

The findings from MAIA add clarity to the efficacy and safety of daratumumab in this setting, building on previous phase 3 myeloma trials in the same area, such as ALCYONE, CASTOR, and POLLUX, the investigators noted.

MAIA was an open-label, international trial involving 737 patients with newly diagnosed multiple myeloma who were ineligible for ASCT. Patients were randomized in a 1:1 ratio to receive either daratumumab, lenalidomide, and dexamethasone (daratumumab group; n = 368) or lenalidomide and dexamethasone alone (control group; n = 369).

On a 28-day cycle, all patients received oral lenalidomide 25 mg on days 1-21 and oral dexamethasone 40 mg on days 1, 8, 15, and 22. Patients in the daratumumab group received intravenous daratumumab dosed at 16 mg/kg once a week for cycles 1 and 2, every 2 weeks for cycles 3-6, and then every 4 weeks thereafter. Treatment was continued until unacceptable toxic effects or disease progression occurred.

The primary end point was progression-free survival (PFS). Various secondary end points were also evaluated, including time to progression, complete responses, overall survival, and others.

Among the 737 randomized patients, 729 ultimately underwent treatment. The median patient age was 73 years.

Generally, efficacy measures favored adding daratumumab. After a median follow-up of 28.0 months, disease progression or death had occurred in 26.4% of patients in the daratumumab group, compared with 38.8% in the control group.

The median PFS was not reached in the daratumumab group, compared with 31.9 months in the control group. There was a 44% lower risk of disease progression or death among patients who received daratumumab, compared with the control group (hazard ratio, 0.56, P less than .001).

This PFS trend was consistent across most subgroups, including those for sex, age, and race, with the exception of patients with baseline hepatic impairment.

Additional efficacy measures added weight to the apparent benefit of adding daratumumab. For instance, more patients in the daratumumab group achieved a complete response or better (47.6% vs. 24.9%) and were negative for minimum residual disease (24.2% vs. 7.3%).

In terms of safety, more patients in the daratumumab group than the control group developed grade 3 or higher neutropenia (50% vs. 35.3%), lymphopenia (15.1% vs. 10.7%), infections (32.1% vs. 23.3%) or pneumonia (13.7% vs. 7.9%).

In contrast, grade 3 or 4 anemia was less common in the daratumumab group than the control group (11.8% vs. 19.7%). Overall, the rate of serious adverse events was similar for both groups (approximately 63%), as was the rate of adverse events resulting in death (approximately 6%-7%).

“In this trial involving patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation, the addition of daratumumab to lenalidomide and dexamethasone resulted in significantly longer progression-free survival, a higher response rate, an increased depth of response, and a longer duration of response than lenalidomide and dexamethasone alone,” the investigators concluded.

The study was funded by Janssen Research and Development. The investigators reported relationships with Janssen, Celgene, Takeda, Sanofi, and other companies.

SOURCE: Facon T et al. N Engl J Med. 2019;380:2104-15.

For patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplantation (ASCT), adding daratumumab to lenalidomide and dexamethasone provides better outcomes than standard therapy alone, based on an interim analysis from the phase 3 MAIA trial.

A greater proportion of patients in the daratumumab group had complete responses and were alive without disease progression after a median follow-up of 28 months, reported lead author Thierry Facon, MD, of the University of Lille (France) and colleagues, who also noted that daratumumab was associated with higher rates of grade 3 or 4 pneumonia, neutropenia, and lymphopenia.

“For patients who are ineligible for stem-cell transplantation, multiagent regimens, including alkylating agents, glucocorticoids, immunomodulatory drugs, proteasome inhibitors, and new agents, are the standard of care,” the investigators wrote in the New England Journal of Medicine.

The findings from MAIA add clarity to the efficacy and safety of daratumumab in this setting, building on previous phase 3 myeloma trials in the same area, such as ALCYONE, CASTOR, and POLLUX, the investigators noted.

MAIA was an open-label, international trial involving 737 patients with newly diagnosed multiple myeloma who were ineligible for ASCT. Patients were randomized in a 1:1 ratio to receive either daratumumab, lenalidomide, and dexamethasone (daratumumab group; n = 368) or lenalidomide and dexamethasone alone (control group; n = 369).

On a 28-day cycle, all patients received oral lenalidomide 25 mg on days 1-21 and oral dexamethasone 40 mg on days 1, 8, 15, and 22. Patients in the daratumumab group received intravenous daratumumab dosed at 16 mg/kg once a week for cycles 1 and 2, every 2 weeks for cycles 3-6, and then every 4 weeks thereafter. Treatment was continued until unacceptable toxic effects or disease progression occurred.

The primary end point was progression-free survival (PFS). Various secondary end points were also evaluated, including time to progression, complete responses, overall survival, and others.

Among the 737 randomized patients, 729 ultimately underwent treatment. The median patient age was 73 years.

Generally, efficacy measures favored adding daratumumab. After a median follow-up of 28.0 months, disease progression or death had occurred in 26.4% of patients in the daratumumab group, compared with 38.8% in the control group.

The median PFS was not reached in the daratumumab group, compared with 31.9 months in the control group. There was a 44% lower risk of disease progression or death among patients who received daratumumab, compared with the control group (hazard ratio, 0.56, P less than .001).

This PFS trend was consistent across most subgroups, including those for sex, age, and race, with the exception of patients with baseline hepatic impairment.

Additional efficacy measures added weight to the apparent benefit of adding daratumumab. For instance, more patients in the daratumumab group achieved a complete response or better (47.6% vs. 24.9%) and were negative for minimum residual disease (24.2% vs. 7.3%).

In terms of safety, more patients in the daratumumab group than the control group developed grade 3 or higher neutropenia (50% vs. 35.3%), lymphopenia (15.1% vs. 10.7%), infections (32.1% vs. 23.3%) or pneumonia (13.7% vs. 7.9%).

In contrast, grade 3 or 4 anemia was less common in the daratumumab group than the control group (11.8% vs. 19.7%). Overall, the rate of serious adverse events was similar for both groups (approximately 63%), as was the rate of adverse events resulting in death (approximately 6%-7%).

“In this trial involving patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation, the addition of daratumumab to lenalidomide and dexamethasone resulted in significantly longer progression-free survival, a higher response rate, an increased depth of response, and a longer duration of response than lenalidomide and dexamethasone alone,” the investigators concluded.

The study was funded by Janssen Research and Development. The investigators reported relationships with Janssen, Celgene, Takeda, Sanofi, and other companies.

SOURCE: Facon T et al. N Engl J Med. 2019;380:2104-15.

Patients with oligometastatic non–small cell lung cancer (NSCLC) have better outcomes when treated with local consolidative therapy than with maintenance therapy or observation, based on updated results from a phase 2 trial.

The randomized study showed that both median progression-free and overall survival were better in patients who received radiotherapy or surgery instead of maintenance therapy or observation, reported lead author Daniel R. Gomez, MD, of the University of Texas MD Anderson Cancer Center, Houston, and colleagues. These findings build on earlier results that showed the positive impact of local consolidative therapy (LCT), the investigators noted.

“The trial was closed early after it demonstrated an observed 8-month benefit in [progression-free survival] for patients who received LCT relative to patients who received maintenance therapy or observation,” the investigators wrote in Journal of Clinical Oncology.

After early closure, 49 patients remained in the dataset. All had metastatic NSCLC with three or fewer metastases that did not progress for at least 3 months after first-line systemic therapy. Most patients had adenocarcinoma (80%). Patients were randomly divided in a 1:1 ratio between radiotherapy or surgery (LCT) for all active disease sites or maintenance therapy/observation (MT/O). Progression-free survival was the primary endpoint. Overall survival and several other secondary endpoints were also evaluated.

Data analysis showed a clear benefit of LCT. Continuing the previously reported trend, median progression-free survival was extended in the LCT group, compared with the MT/O group (14.2 vs. 4.4 months; P = .022). Similarly, median overall survival showed a significant improvement (41.2 vs. 17.0 months; P = .017). Median time to appearance of new lesions also supported the advantage of LCT over MT/O, albeit with less statistical significance (14.2 vs. 6.0 months; P = .11).

The investigators suggested several mechanisms behind the efficacy of LCT, including elimination of treatment-resistant cells, potentiation of systemic therapy, and elimination of the residual tumor as a driver of distant micrometastatic disease. “Notably,” the investigators wrote, “these mechanisms are not mutually exclusive, and more than one could contribute to the benefits of LCT.”

“[A]lthough these data are compelling ... we emphasize that future studies should be supported to definitively assess the role of LCT in larger populations (e.g., phase III trials such as NRG-LU002) and in the context of novel systemic therapies,” the investigators concluded.

The study was funded by MD Anderson Cancer Center, The Mohaymen Sahebzadah Family Philanthropic Grant, and the National Cancer Institute, National Institutes of Health. The authors disclosed relationships with Merck, Bristol-Myers Squibb, AstraZeneca, and others.

SOURCE: Gomez et al. J Clin Oncol. 8 May 2019. doi:10.1200/JCO.19.00201.

Patients with oligometastatic non–small cell lung cancer (NSCLC) have better outcomes when treated with local consolidative therapy than with maintenance therapy or observation, based on updated results from a phase 2 trial.

The randomized study showed that both median progression-free and overall survival were better in patients who received radiotherapy or surgery instead of maintenance therapy or observation, reported lead author Daniel R. Gomez, MD, of the University of Texas MD Anderson Cancer Center, Houston, and colleagues. These findings build on earlier results that showed the positive impact of local consolidative therapy (LCT), the investigators noted.

“The trial was closed early after it demonstrated an observed 8-month benefit in [progression-free survival] for patients who received LCT relative to patients who received maintenance therapy or observation,” the investigators wrote in Journal of Clinical Oncology.

After early closure, 49 patients remained in the dataset. All had metastatic NSCLC with three or fewer metastases that did not progress for at least 3 months after first-line systemic therapy. Most patients had adenocarcinoma (80%). Patients were randomly divided in a 1:1 ratio between radiotherapy or surgery (LCT) for all active disease sites or maintenance therapy/observation (MT/O). Progression-free survival was the primary endpoint. Overall survival and several other secondary endpoints were also evaluated.

Data analysis showed a clear benefit of LCT. Continuing the previously reported trend, median progression-free survival was extended in the LCT group, compared with the MT/O group (14.2 vs. 4.4 months; P = .022). Similarly, median overall survival showed a significant improvement (41.2 vs. 17.0 months; P = .017). Median time to appearance of new lesions also supported the advantage of LCT over MT/O, albeit with less statistical significance (14.2 vs. 6.0 months; P = .11).

The investigators suggested several mechanisms behind the efficacy of LCT, including elimination of treatment-resistant cells, potentiation of systemic therapy, and elimination of the residual tumor as a driver of distant micrometastatic disease. “Notably,” the investigators wrote, “these mechanisms are not mutually exclusive, and more than one could contribute to the benefits of LCT.”

“[A]lthough these data are compelling ... we emphasize that future studies should be supported to definitively assess the role of LCT in larger populations (e.g., phase III trials such as NRG-LU002) and in the context of novel systemic therapies,” the investigators concluded.

The study was funded by MD Anderson Cancer Center, The Mohaymen Sahebzadah Family Philanthropic Grant, and the National Cancer Institute, National Institutes of Health. The authors disclosed relationships with Merck, Bristol-Myers Squibb, AstraZeneca, and others.

SOURCE: Gomez et al. J Clin Oncol. 8 May 2019. doi:10.1200/JCO.19.00201.

Patients with oligometastatic non–small cell lung cancer (NSCLC) have better outcomes when treated with local consolidative therapy than with maintenance therapy or observation, based on updated results from a phase 2 trial.

The randomized study showed that both median progression-free and overall survival were better in patients who received radiotherapy or surgery instead of maintenance therapy or observation, reported lead author Daniel R. Gomez, MD, of the University of Texas MD Anderson Cancer Center, Houston, and colleagues. These findings build on earlier results that showed the positive impact of local consolidative therapy (LCT), the investigators noted.

“The trial was closed early after it demonstrated an observed 8-month benefit in [progression-free survival] for patients who received LCT relative to patients who received maintenance therapy or observation,” the investigators wrote in Journal of Clinical Oncology.

After early closure, 49 patients remained in the dataset. All had metastatic NSCLC with three or fewer metastases that did not progress for at least 3 months after first-line systemic therapy. Most patients had adenocarcinoma (80%). Patients were randomly divided in a 1:1 ratio between radiotherapy or surgery (LCT) for all active disease sites or maintenance therapy/observation (MT/O). Progression-free survival was the primary endpoint. Overall survival and several other secondary endpoints were also evaluated.

Data analysis showed a clear benefit of LCT. Continuing the previously reported trend, median progression-free survival was extended in the LCT group, compared with the MT/O group (14.2 vs. 4.4 months; P = .022). Similarly, median overall survival showed a significant improvement (41.2 vs. 17.0 months; P = .017). Median time to appearance of new lesions also supported the advantage of LCT over MT/O, albeit with less statistical significance (14.2 vs. 6.0 months; P = .11).

The investigators suggested several mechanisms behind the efficacy of LCT, including elimination of treatment-resistant cells, potentiation of systemic therapy, and elimination of the residual tumor as a driver of distant micrometastatic disease. “Notably,” the investigators wrote, “these mechanisms are not mutually exclusive, and more than one could contribute to the benefits of LCT.”

“[A]lthough these data are compelling ... we emphasize that future studies should be supported to definitively assess the role of LCT in larger populations (e.g., phase III trials such as NRG-LU002) and in the context of novel systemic therapies,” the investigators concluded.

The study was funded by MD Anderson Cancer Center, The Mohaymen Sahebzadah Family Philanthropic Grant, and the National Cancer Institute, National Institutes of Health. The authors disclosed relationships with Merck, Bristol-Myers Squibb, AstraZeneca, and others.

SOURCE: Gomez et al. J Clin Oncol. 8 May 2019. doi:10.1200/JCO.19.00201.

Patients with mild asthma who rely solely on short-acting beta2-agonists (SABAs) to control their asthma symptoms remain at increased risk of exacerbations, according to investigators.

Two recent studies presented at the American Thoracic Society’s international conference demonstrated the benefits of glucocorticoid therapy among patients with mild persistent or intermittent asthma while highlighting differential responses to steroids among patients with high versus low levels of eosinophils in sputum. Both studies were simultaneously published in the New England Journal of Medicine.

The first study, SIENA, led by Stephen C. Lazarus, MD of the University of California, San Francisco, and colleagues, involved 295 patients with mild, persistent asthma. Patients were classified as having either a high or low level of eosinophils in sputum, with a low level defined by two sputum samples consisting of less than 2% eosinophils. After a single-blind placebo run-in period of 6 weeks, patients were randomized to receive either mometasone (an inhaled glucocorticoid), tiotropium (a long-acting muscarinic antagonist [LAMA]), or placebo for 12 weeks each, with subsequent crossover through the two remaining treatments. The primary outcome was the response to each active agent, compared with placebo among low-eosinophil patients who had a differential response to a trial agent.

Out of 295 patients, 221 (75%) had low eosinophils and 74 (25%) had high eosinophils. In the low-eosinophil subgroup, 59% of patients had a differential response to a trial agent; among these, 57% responded better to mometasone, compared with 43% who responded better to placebo, and 60% responded better to tiotropium, compared with 40% who responded better to placebo.

Turning to secondary analyses, among patients with high eosinophil levels who had a differential response, 74% responded better to mometasone, compared with 26% who responded better to placebo, and 57% responded better to tiotropium, compared with 43% who responded better to placebo.

In an additional exploratory analysis, adults with low eosinophil levels had better responses to tiotropium than placebo (62% vs 38%).

The researchers stated that a key finding of the study is that three-quarters of the mild, persistent asthma population had low eosinophil levels, far fewer than expected and that the difference in their response to mometasone compared to tiotropium was not significant.

“Our results raise the question of whether treatment guidelines should be reevaluated for patients with mild, persistent asthma for whom evidence of type 2 inflammation is lacking,” the investigators wrote. “The need for a change in treatment strategy is further highlighted by a growing body of literature suggesting that mild, persistent asthma can be managed safely without the daily use of inhaled glucocorticoids and by data showing that patients with a low eosinophil level may not have a favorable response to inhaled glucocorticoids” (New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1814917).

The second study, Novel START, conducted by lead author Richard Beasley, DSc, of the Medical Research Institute of New Zealand, Wellington, and colleagues, compared the efficacy of two inhaled glucocorticoid regimens and albuterol alone for patients with mild persistent or intermittent asthma, measured by annualized exacerbation rate.

Initial randomization involved 675 patients, of whom 668 were included in the final analysis. Patients were randomized into three groups: albuterol as needed (100 mcg, two inhalations as needed for asthma symptoms), budesonide maintenance (200 mcg, one inhalation twice daily with as-needed albuterol), or budesonide/formoterol (budesonide 200 mcg and formoterol 6 mcg, one inhalation as needed). Along with annualized exacerbation rate, several secondary outcomes assessed symptoms, respiratory function, and number of severe exacerbations.

Data analysis showed that patients in the budesonide groups had similar rates of annualized exacerbation, both of which were significantly better than the exacerbation rate in the albuterol-only group; the absolute rate of exacerbations per patient per year was 0.175, 0.195, and 0.400 for budesonide maintenance, budesonide/formoterol, and albuterol only, respectively. Similarly, the median fraction of exhaled nitric oxide (FENO) was lower in the budesonide groups than in the albuterol-only group. Patients in the budesonide/formoterol group had a 56% lower relative risk of severe pulmonary exacerbation than patients in the budesonide maintenance group and a 60% lower relative risk than the albuterol group. However, maintenance budesonide provided better symptom relief than budesonide/formoterol, “which suggests that for the patient for whom asthma symptoms rather than exacerbations are the most bothersome, maintenance treatment has value,” the investigators wrote (New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1901963).

“The findings of our trial are consistent with evidence regarding the treatment of moderate and severe asthma – that maintenance and reliever therapy” with inhaled glucocorticoid/formoterol “results in a lower risk of severe exacerbations than maintenance therapy with an inhaled glucocorticoid–[long-acting beta agonist] and as-needed SABA,” the investigators concluded.

SIENA was funded by National Heart, Lung, and Blood Institute, with medications provided by Boehringer Ingelheim, Merck, and Teva; the investigators reported relationships with Sanofi, Vectura, Circassia, DBV Technologies, and others. Novel START was funded by AstraZeneca and the Health Research Council of New Zealand; the investigators reported relationships with GlaxoSmithKline, Genentech, Theravance Biopharma, and others.

SOURCES: Beasley et al. New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1901963; Lazarus et al. New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1814917.

Patients with mild asthma who rely solely on short-acting beta2-agonists (SABAs) to control their asthma symptoms remain at increased risk of exacerbations, according to investigators.

Two recent studies presented at the American Thoracic Society’s international conference demonstrated the benefits of glucocorticoid therapy among patients with mild persistent or intermittent asthma while highlighting differential responses to steroids among patients with high versus low levels of eosinophils in sputum. Both studies were simultaneously published in the New England Journal of Medicine.

The first study, SIENA, led by Stephen C. Lazarus, MD of the University of California, San Francisco, and colleagues, involved 295 patients with mild, persistent asthma. Patients were classified as having either a high or low level of eosinophils in sputum, with a low level defined by two sputum samples consisting of less than 2% eosinophils. After a single-blind placebo run-in period of 6 weeks, patients were randomized to receive either mometasone (an inhaled glucocorticoid), tiotropium (a long-acting muscarinic antagonist [LAMA]), or placebo for 12 weeks each, with subsequent crossover through the two remaining treatments. The primary outcome was the response to each active agent, compared with placebo among low-eosinophil patients who had a differential response to a trial agent.

Out of 295 patients, 221 (75%) had low eosinophils and 74 (25%) had high eosinophils. In the low-eosinophil subgroup, 59% of patients had a differential response to a trial agent; among these, 57% responded better to mometasone, compared with 43% who responded better to placebo, and 60% responded better to tiotropium, compared with 40% who responded better to placebo.

Turning to secondary analyses, among patients with high eosinophil levels who had a differential response, 74% responded better to mometasone, compared with 26% who responded better to placebo, and 57% responded better to tiotropium, compared with 43% who responded better to placebo.

In an additional exploratory analysis, adults with low eosinophil levels had better responses to tiotropium than placebo (62% vs 38%).

The researchers stated that a key finding of the study is that three-quarters of the mild, persistent asthma population had low eosinophil levels, far fewer than expected and that the difference in their response to mometasone compared to tiotropium was not significant.

“Our results raise the question of whether treatment guidelines should be reevaluated for patients with mild, persistent asthma for whom evidence of type 2 inflammation is lacking,” the investigators wrote. “The need for a change in treatment strategy is further highlighted by a growing body of literature suggesting that mild, persistent asthma can be managed safely without the daily use of inhaled glucocorticoids and by data showing that patients with a low eosinophil level may not have a favorable response to inhaled glucocorticoids” (New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1814917).

The second study, Novel START, conducted by lead author Richard Beasley, DSc, of the Medical Research Institute of New Zealand, Wellington, and colleagues, compared the efficacy of two inhaled glucocorticoid regimens and albuterol alone for patients with mild persistent or intermittent asthma, measured by annualized exacerbation rate.

Initial randomization involved 675 patients, of whom 668 were included in the final analysis. Patients were randomized into three groups: albuterol as needed (100 mcg, two inhalations as needed for asthma symptoms), budesonide maintenance (200 mcg, one inhalation twice daily with as-needed albuterol), or budesonide/formoterol (budesonide 200 mcg and formoterol 6 mcg, one inhalation as needed). Along with annualized exacerbation rate, several secondary outcomes assessed symptoms, respiratory function, and number of severe exacerbations.

Data analysis showed that patients in the budesonide groups had similar rates of annualized exacerbation, both of which were significantly better than the exacerbation rate in the albuterol-only group; the absolute rate of exacerbations per patient per year was 0.175, 0.195, and 0.400 for budesonide maintenance, budesonide/formoterol, and albuterol only, respectively. Similarly, the median fraction of exhaled nitric oxide (FENO) was lower in the budesonide groups than in the albuterol-only group. Patients in the budesonide/formoterol group had a 56% lower relative risk of severe pulmonary exacerbation than patients in the budesonide maintenance group and a 60% lower relative risk than the albuterol group. However, maintenance budesonide provided better symptom relief than budesonide/formoterol, “which suggests that for the patient for whom asthma symptoms rather than exacerbations are the most bothersome, maintenance treatment has value,” the investigators wrote (New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1901963).

“The findings of our trial are consistent with evidence regarding the treatment of moderate and severe asthma – that maintenance and reliever therapy” with inhaled glucocorticoid/formoterol “results in a lower risk of severe exacerbations than maintenance therapy with an inhaled glucocorticoid–[long-acting beta agonist] and as-needed SABA,” the investigators concluded.

SIENA was funded by National Heart, Lung, and Blood Institute, with medications provided by Boehringer Ingelheim, Merck, and Teva; the investigators reported relationships with Sanofi, Vectura, Circassia, DBV Technologies, and others. Novel START was funded by AstraZeneca and the Health Research Council of New Zealand; the investigators reported relationships with GlaxoSmithKline, Genentech, Theravance Biopharma, and others.

SOURCES: Beasley et al. New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1901963; Lazarus et al. New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1814917.

Patients with mild asthma who rely solely on short-acting beta2-agonists (SABAs) to control their asthma symptoms remain at increased risk of exacerbations, according to investigators.

Two recent studies presented at the American Thoracic Society’s international conference demonstrated the benefits of glucocorticoid therapy among patients with mild persistent or intermittent asthma while highlighting differential responses to steroids among patients with high versus low levels of eosinophils in sputum. Both studies were simultaneously published in the New England Journal of Medicine.

The first study, SIENA, led by Stephen C. Lazarus, MD of the University of California, San Francisco, and colleagues, involved 295 patients with mild, persistent asthma. Patients were classified as having either a high or low level of eosinophils in sputum, with a low level defined by two sputum samples consisting of less than 2% eosinophils. After a single-blind placebo run-in period of 6 weeks, patients were randomized to receive either mometasone (an inhaled glucocorticoid), tiotropium (a long-acting muscarinic antagonist [LAMA]), or placebo for 12 weeks each, with subsequent crossover through the two remaining treatments. The primary outcome was the response to each active agent, compared with placebo among low-eosinophil patients who had a differential response to a trial agent.

Out of 295 patients, 221 (75%) had low eosinophils and 74 (25%) had high eosinophils. In the low-eosinophil subgroup, 59% of patients had a differential response to a trial agent; among these, 57% responded better to mometasone, compared with 43% who responded better to placebo, and 60% responded better to tiotropium, compared with 40% who responded better to placebo.

Turning to secondary analyses, among patients with high eosinophil levels who had a differential response, 74% responded better to mometasone, compared with 26% who responded better to placebo, and 57% responded better to tiotropium, compared with 43% who responded better to placebo.

In an additional exploratory analysis, adults with low eosinophil levels had better responses to tiotropium than placebo (62% vs 38%).

The researchers stated that a key finding of the study is that three-quarters of the mild, persistent asthma population had low eosinophil levels, far fewer than expected and that the difference in their response to mometasone compared to tiotropium was not significant.

“Our results raise the question of whether treatment guidelines should be reevaluated for patients with mild, persistent asthma for whom evidence of type 2 inflammation is lacking,” the investigators wrote. “The need for a change in treatment strategy is further highlighted by a growing body of literature suggesting that mild, persistent asthma can be managed safely without the daily use of inhaled glucocorticoids and by data showing that patients with a low eosinophil level may not have a favorable response to inhaled glucocorticoids” (New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1814917).

The second study, Novel START, conducted by lead author Richard Beasley, DSc, of the Medical Research Institute of New Zealand, Wellington, and colleagues, compared the efficacy of two inhaled glucocorticoid regimens and albuterol alone for patients with mild persistent or intermittent asthma, measured by annualized exacerbation rate.

Initial randomization involved 675 patients, of whom 668 were included in the final analysis. Patients were randomized into three groups: albuterol as needed (100 mcg, two inhalations as needed for asthma symptoms), budesonide maintenance (200 mcg, one inhalation twice daily with as-needed albuterol), or budesonide/formoterol (budesonide 200 mcg and formoterol 6 mcg, one inhalation as needed). Along with annualized exacerbation rate, several secondary outcomes assessed symptoms, respiratory function, and number of severe exacerbations.

Data analysis showed that patients in the budesonide groups had similar rates of annualized exacerbation, both of which were significantly better than the exacerbation rate in the albuterol-only group; the absolute rate of exacerbations per patient per year was 0.175, 0.195, and 0.400 for budesonide maintenance, budesonide/formoterol, and albuterol only, respectively. Similarly, the median fraction of exhaled nitric oxide (FENO) was lower in the budesonide groups than in the albuterol-only group. Patients in the budesonide/formoterol group had a 56% lower relative risk of severe pulmonary exacerbation than patients in the budesonide maintenance group and a 60% lower relative risk than the albuterol group. However, maintenance budesonide provided better symptom relief than budesonide/formoterol, “which suggests that for the patient for whom asthma symptoms rather than exacerbations are the most bothersome, maintenance treatment has value,” the investigators wrote (New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1901963).

“The findings of our trial are consistent with evidence regarding the treatment of moderate and severe asthma – that maintenance and reliever therapy” with inhaled glucocorticoid/formoterol “results in a lower risk of severe exacerbations than maintenance therapy with an inhaled glucocorticoid–[long-acting beta agonist] and as-needed SABA,” the investigators concluded.

SIENA was funded by National Heart, Lung, and Blood Institute, with medications provided by Boehringer Ingelheim, Merck, and Teva; the investigators reported relationships with Sanofi, Vectura, Circassia, DBV Technologies, and others. Novel START was funded by AstraZeneca and the Health Research Council of New Zealand; the investigators reported relationships with GlaxoSmithKline, Genentech, Theravance Biopharma, and others.

SOURCES: Beasley et al. New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1901963; Lazarus et al. New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1814917.

For patients with oropharyngeal squamous cell carcinoma (OPSCC), initial staging with PET is associated with better cancer-specific survival (CSS) than staging with other imaging modalities, based on a retrospective analysis of more than 1,700 patients.

PET was associated with a better 3-year overall survival rate than either MRI without PET or CT alone, reported lead author Rustain L. Morgan, MD, of the University of Colorado at Denver, Aurora, and colleagues.

“To our knowledge, there have been no prospective, randomized, controlled trials to date to evaluate the effect of different imaging modalities at the time of initial staging on cancer-specific survival,” the investigators wrote in Cancer. “A population-based data source such as the Surveillance, Epidemiology, and End Results [SEER]–Medicare database provides an excellent opportunity to compare the impact of imaging modality differences on survival in patients with OPSCC.”

Using SEER data, the investigators identified more than 3,704 patients with oropharyngeal cancer; following exclusions, 1,765 patients were involved in the final analysis based on various factors, including survival beyond 2 months after diagnosis and squamous cell carcinoma histology. A Cox proportional hazards model was used to assess relationships between the primary outcome and 3-year CSS rate and imaging, sex, age, region, race, and education.

Results showed that most patients had PET imaging upon diagnosis (83.3%), while fewer had CT alone (11.4%) or MRI without PET (5.2%). Several underlying trends were found: Patients in the West were more likely to undergo PET than patients in the Midwest, South, or East; patients younger than 75 years were more likely to have PET than older patients; and men were more likely to be staged with PET than women. The 3-year CSS was longest for patients who underwent PET (56.8%), followed by MRI without PET (50.1%) and CT alone (47.3%). Controlling for treatment and stage of disease, multivariate analysis also suggested that PET is associated with better CSS; patients staged with MRI without PET had a hazard ratio of 1.748 (P = .0036) and those imaged with CT alone had an HR of 1.337 (P = .0491). Although the Cox proportional hazards model for overall survival revealed numerical trends, these lacked statistical significance for MRI without PET (HR, 1.365; P =.0683) and CT alone (HR, 1.213; P = .114).

“The current study demonstrated a significant difference in CSS based on initial imaging,” the investigators wrote. “These findings are consistent with a prior study that reported that PET imaging can improve the staging of patients with head and neck cancers, particularly as it relates to radiotherapy planning.

“The data from the current study suggest the need for further prospective research to evaluate whether CT or MRI should be considered adequate for the initial staging of patients with OPSCC,” the investigators concluded.

The study was funded by the University of Colorado Cancer Center. One coauthor reported relationships with the American Heart Association and the National Heart, Lung, and Blood Institute.

SOURCE: Morgan RL et al. Cancer. 2019 May 1. doi:10.1002/cncr.32148.

For patients with oropharyngeal squamous cell carcinoma (OPSCC), initial staging with PET is associated with better cancer-specific survival (CSS) than staging with other imaging modalities, based on a retrospective analysis of more than 1,700 patients.

PET was associated with a better 3-year overall survival rate than either MRI without PET or CT alone, reported lead author Rustain L. Morgan, MD, of the University of Colorado at Denver, Aurora, and colleagues.

“To our knowledge, there have been no prospective, randomized, controlled trials to date to evaluate the effect of different imaging modalities at the time of initial staging on cancer-specific survival,” the investigators wrote in Cancer. “A population-based data source such as the Surveillance, Epidemiology, and End Results [SEER]–Medicare database provides an excellent opportunity to compare the impact of imaging modality differences on survival in patients with OPSCC.”

Using SEER data, the investigators identified more than 3,704 patients with oropharyngeal cancer; following exclusions, 1,765 patients were involved in the final analysis based on various factors, including survival beyond 2 months after diagnosis and squamous cell carcinoma histology. A Cox proportional hazards model was used to assess relationships between the primary outcome and 3-year CSS rate and imaging, sex, age, region, race, and education.

Results showed that most patients had PET imaging upon diagnosis (83.3%), while fewer had CT alone (11.4%) or MRI without PET (5.2%). Several underlying trends were found: Patients in the West were more likely to undergo PET than patients in the Midwest, South, or East; patients younger than 75 years were more likely to have PET than older patients; and men were more likely to be staged with PET than women. The 3-year CSS was longest for patients who underwent PET (56.8%), followed by MRI without PET (50.1%) and CT alone (47.3%). Controlling for treatment and stage of disease, multivariate analysis also suggested that PET is associated with better CSS; patients staged with MRI without PET had a hazard ratio of 1.748 (P = .0036) and those imaged with CT alone had an HR of 1.337 (P = .0491). Although the Cox proportional hazards model for overall survival revealed numerical trends, these lacked statistical significance for MRI without PET (HR, 1.365; P =.0683) and CT alone (HR, 1.213; P = .114).

“The current study demonstrated a significant difference in CSS based on initial imaging,” the investigators wrote. “These findings are consistent with a prior study that reported that PET imaging can improve the staging of patients with head and neck cancers, particularly as it relates to radiotherapy planning.

“The data from the current study suggest the need for further prospective research to evaluate whether CT or MRI should be considered adequate for the initial staging of patients with OPSCC,” the investigators concluded.

The study was funded by the University of Colorado Cancer Center. One coauthor reported relationships with the American Heart Association and the National Heart, Lung, and Blood Institute.

SOURCE: Morgan RL et al. Cancer. 2019 May 1. doi:10.1002/cncr.32148.

For patients with oropharyngeal squamous cell carcinoma (OPSCC), initial staging with PET is associated with better cancer-specific survival (CSS) than staging with other imaging modalities, based on a retrospective analysis of more than 1,700 patients.

PET was associated with a better 3-year overall survival rate than either MRI without PET or CT alone, reported lead author Rustain L. Morgan, MD, of the University of Colorado at Denver, Aurora, and colleagues.

“To our knowledge, there have been no prospective, randomized, controlled trials to date to evaluate the effect of different imaging modalities at the time of initial staging on cancer-specific survival,” the investigators wrote in Cancer. “A population-based data source such as the Surveillance, Epidemiology, and End Results [SEER]–Medicare database provides an excellent opportunity to compare the impact of imaging modality differences on survival in patients with OPSCC.”

Using SEER data, the investigators identified more than 3,704 patients with oropharyngeal cancer; following exclusions, 1,765 patients were involved in the final analysis based on various factors, including survival beyond 2 months after diagnosis and squamous cell carcinoma histology. A Cox proportional hazards model was used to assess relationships between the primary outcome and 3-year CSS rate and imaging, sex, age, region, race, and education.

Results showed that most patients had PET imaging upon diagnosis (83.3%), while fewer had CT alone (11.4%) or MRI without PET (5.2%). Several underlying trends were found: Patients in the West were more likely to undergo PET than patients in the Midwest, South, or East; patients younger than 75 years were more likely to have PET than older patients; and men were more likely to be staged with PET than women. The 3-year CSS was longest for patients who underwent PET (56.8%), followed by MRI without PET (50.1%) and CT alone (47.3%). Controlling for treatment and stage of disease, multivariate analysis also suggested that PET is associated with better CSS; patients staged with MRI without PET had a hazard ratio of 1.748 (P = .0036) and those imaged with CT alone had an HR of 1.337 (P = .0491). Although the Cox proportional hazards model for overall survival revealed numerical trends, these lacked statistical significance for MRI without PET (HR, 1.365; P =.0683) and CT alone (HR, 1.213; P = .114).

“The current study demonstrated a significant difference in CSS based on initial imaging,” the investigators wrote. “These findings are consistent with a prior study that reported that PET imaging can improve the staging of patients with head and neck cancers, particularly as it relates to radiotherapy planning.

“The data from the current study suggest the need for further prospective research to evaluate whether CT or MRI should be considered adequate for the initial staging of patients with OPSCC,” the investigators concluded.

The study was funded by the University of Colorado Cancer Center. One coauthor reported relationships with the American Heart Association and the National Heart, Lung, and Blood Institute.

SOURCE: Morgan RL et al. Cancer. 2019 May 1. doi:10.1002/cncr.32148.