Hematologic Malignancies

High-dose therapy with melphalan followed by autologous stem cell transplant (HDT/ASCT) is still the best option for multiple myeloma even after almost 2 decades with newer and highly effective induction agents, according to a recent systematic review and two meta-analyses.

Given the “unprecedented efficacy” of “modern induction therapy with immunomodulatory drugs and proteasome inhibitors (also called ‘novel agents’),” investigators “have sought to reevaluate the role of HDT/ASCT,” wrote Binod Dhakal, MD, of the Medical College of Wisconsin, and his colleagues. The report is in JAMA Oncology.

To solve the issue, they analyzed five randomized controlled trials conducted since 2000 and concluded that HDT/ASCT is still the preferred treatment approach.

Despite a lack of demonstrable overall survival benefit, there is a significant progression-free survival (PFS) benefit, low treatment-related mortality, and potential high minimal residual disease-negative rates conferred by HDT/ASCT in newly-diagnosed multiple myeloma, the researchers noted.

The combined odds for complete response were 1.27 (95% confidence interval, 0.97-1.65, P = .07) with HDT/ASCT, compared with standard-dose therapy (SDT). The combined hazard ratio (HR) for PFS was 0.55 (95% CI, 0.41-0.7, P less than .001) and 0.76 for overall survival (95% CI, 0.42-1.36, P = .20) in favor of HDT.

PFS was best with tandem HDT/ASCT (HR, 0.49, 95% CI, 0.37-0.65) followed by single HDT/ASCT with bortezomib, lenalidomide, and dexamethasone consolidation (HR, 0.53, 95% CI, 0.37-0.76) and single HDT/ASCT alone (HR, 0.68, 95% CI, 0.53-0.87), compared with SDT. However, none of the HDT/ASCT approaches had a significant impact on overall survival.

Meanwhile, treatment-related mortality with HDT/ASCT was minimal, at less than 1%.

“The achievement of high [minimal residual disease] rates with HDT/ASCT may render this approach the ideal platform for testing novel approaches (e.g., immunotherapy) aiming at disease eradication and cures,” the researchers wrote.

The researchers reported relationships with a number of companies, including Takeda, Celgene, and Amgen, that make novel induction agents.

aotto@frontlinemedcom.com

SOURCE: Dhakal B et al. JAMA Oncol. 2018 Jan 4. doi: 10.1001/jamaoncol.2017.4600.

High-dose therapy with melphalan followed by autologous stem cell transplant (HDT/ASCT) is still the best option for multiple myeloma even after almost 2 decades with newer and highly effective induction agents, according to a recent systematic review and two meta-analyses.

Given the “unprecedented efficacy” of “modern induction therapy with immunomodulatory drugs and proteasome inhibitors (also called ‘novel agents’),” investigators “have sought to reevaluate the role of HDT/ASCT,” wrote Binod Dhakal, MD, of the Medical College of Wisconsin, and his colleagues. The report is in JAMA Oncology.

To solve the issue, they analyzed five randomized controlled trials conducted since 2000 and concluded that HDT/ASCT is still the preferred treatment approach.

Despite a lack of demonstrable overall survival benefit, there is a significant progression-free survival (PFS) benefit, low treatment-related mortality, and potential high minimal residual disease-negative rates conferred by HDT/ASCT in newly-diagnosed multiple myeloma, the researchers noted.

The combined odds for complete response were 1.27 (95% confidence interval, 0.97-1.65, P = .07) with HDT/ASCT, compared with standard-dose therapy (SDT). The combined hazard ratio (HR) for PFS was 0.55 (95% CI, 0.41-0.7, P less than .001) and 0.76 for overall survival (95% CI, 0.42-1.36, P = .20) in favor of HDT.

PFS was best with tandem HDT/ASCT (HR, 0.49, 95% CI, 0.37-0.65) followed by single HDT/ASCT with bortezomib, lenalidomide, and dexamethasone consolidation (HR, 0.53, 95% CI, 0.37-0.76) and single HDT/ASCT alone (HR, 0.68, 95% CI, 0.53-0.87), compared with SDT. However, none of the HDT/ASCT approaches had a significant impact on overall survival.

Meanwhile, treatment-related mortality with HDT/ASCT was minimal, at less than 1%.

“The achievement of high [minimal residual disease] rates with HDT/ASCT may render this approach the ideal platform for testing novel approaches (e.g., immunotherapy) aiming at disease eradication and cures,” the researchers wrote.

The researchers reported relationships with a number of companies, including Takeda, Celgene, and Amgen, that make novel induction agents.

aotto@frontlinemedcom.com

SOURCE: Dhakal B et al. JAMA Oncol. 2018 Jan 4. doi: 10.1001/jamaoncol.2017.4600.

High-dose therapy with melphalan followed by autologous stem cell transplant (HDT/ASCT) is still the best option for multiple myeloma even after almost 2 decades with newer and highly effective induction agents, according to a recent systematic review and two meta-analyses.

Given the “unprecedented efficacy” of “modern induction therapy with immunomodulatory drugs and proteasome inhibitors (also called ‘novel agents’),” investigators “have sought to reevaluate the role of HDT/ASCT,” wrote Binod Dhakal, MD, of the Medical College of Wisconsin, and his colleagues. The report is in JAMA Oncology.

To solve the issue, they analyzed five randomized controlled trials conducted since 2000 and concluded that HDT/ASCT is still the preferred treatment approach.

Despite a lack of demonstrable overall survival benefit, there is a significant progression-free survival (PFS) benefit, low treatment-related mortality, and potential high minimal residual disease-negative rates conferred by HDT/ASCT in newly-diagnosed multiple myeloma, the researchers noted.

The combined odds for complete response were 1.27 (95% confidence interval, 0.97-1.65, P = .07) with HDT/ASCT, compared with standard-dose therapy (SDT). The combined hazard ratio (HR) for PFS was 0.55 (95% CI, 0.41-0.7, P less than .001) and 0.76 for overall survival (95% CI, 0.42-1.36, P = .20) in favor of HDT.

PFS was best with tandem HDT/ASCT (HR, 0.49, 95% CI, 0.37-0.65) followed by single HDT/ASCT with bortezomib, lenalidomide, and dexamethasone consolidation (HR, 0.53, 95% CI, 0.37-0.76) and single HDT/ASCT alone (HR, 0.68, 95% CI, 0.53-0.87), compared with SDT. However, none of the HDT/ASCT approaches had a significant impact on overall survival.

Meanwhile, treatment-related mortality with HDT/ASCT was minimal, at less than 1%.

“The achievement of high [minimal residual disease] rates with HDT/ASCT may render this approach the ideal platform for testing novel approaches (e.g., immunotherapy) aiming at disease eradication and cures,” the researchers wrote.

The researchers reported relationships with a number of companies, including Takeda, Celgene, and Amgen, that make novel induction agents.

aotto@frontlinemedcom.com

SOURCE: Dhakal B et al. JAMA Oncol. 2018 Jan 4. doi: 10.1001/jamaoncol.2017.4600.

Adult patients with mycosis fungoides (MF) have a higher risk of secondary malignancies, according to a 20-year population-based cohort study. The researchers, from Bezmialem Vakif University in Istanbul, Turkey, say their findings support earlier research about a higher risk of, for instance, Hodgkin lymphoma, chronic leukemia, and lung cancer.

Between 1998 and 2015, the researchers documented 143 cases of cutaneous T-cell lymphoma (CTCL). The majority of patients had early-stage disease.

The researchers also documented 13 cases (9%) of secondary malignancy diagnosed at least 3 months after the diagnosis of CTCL. The cancers included bladder cancer, nasopharynx cancer, renal cell carcinoma, lung cancer, and superficial spreading malignant melanoma.

Older age, stage IV disease, lymphomatoid papulosis, and having CTCL for > 10 years raised the chances of developing secondary solid tumors. In 60% of patients, the secondary malignancies occurred during the first year of diagnosis.

Research has suggested that antilymphoma drugs, particularly alkylating agents, may lead to leukemia, the researchers note. In this study, 6 patients with secondary cancers were getting systemic treatment with interferon or acitretin; 7 were getting no systemic treatment.

The researchers add that MF and hematologic malignancies may share genetic origin, carcinogens, or viruses that affect lymphocyte precursors. They also note that the first neoplasm may produce cytokines that induce development of the secondary neoplasm. The researchers cite research that found MF is a T helper cell 2–mediated disease associated with human leukocyte antigen 2 alleles. Viruses such as Epstein-Barr and herpes simplex also have been implicated.

“Extensive evaluation” for secondary malignancies in adult patients with MF is wise, the researchers advise, particularly if the patient has lymphomatoid papulosis.

Source:

Cengiz FP, Emiroğlu N, Onsun N. Turk J Haematol. 2017;34(4):378-379.

doi: 10.4274/tjh.2017.0234.

Adult patients with mycosis fungoides (MF) have a higher risk of secondary malignancies, according to a 20-year population-based cohort study. The researchers, from Bezmialem Vakif University in Istanbul, Turkey, say their findings support earlier research about a higher risk of, for instance, Hodgkin lymphoma, chronic leukemia, and lung cancer.

Between 1998 and 2015, the researchers documented 143 cases of cutaneous T-cell lymphoma (CTCL). The majority of patients had early-stage disease.

The researchers also documented 13 cases (9%) of secondary malignancy diagnosed at least 3 months after the diagnosis of CTCL. The cancers included bladder cancer, nasopharynx cancer, renal cell carcinoma, lung cancer, and superficial spreading malignant melanoma.

Older age, stage IV disease, lymphomatoid papulosis, and having CTCL for > 10 years raised the chances of developing secondary solid tumors. In 60% of patients, the secondary malignancies occurred during the first year of diagnosis.

Research has suggested that antilymphoma drugs, particularly alkylating agents, may lead to leukemia, the researchers note. In this study, 6 patients with secondary cancers were getting systemic treatment with interferon or acitretin; 7 were getting no systemic treatment.

The researchers add that MF and hematologic malignancies may share genetic origin, carcinogens, or viruses that affect lymphocyte precursors. They also note that the first neoplasm may produce cytokines that induce development of the secondary neoplasm. The researchers cite research that found MF is a T helper cell 2–mediated disease associated with human leukocyte antigen 2 alleles. Viruses such as Epstein-Barr and herpes simplex also have been implicated.

“Extensive evaluation” for secondary malignancies in adult patients with MF is wise, the researchers advise, particularly if the patient has lymphomatoid papulosis.

Source:

Cengiz FP, Emiroğlu N, Onsun N. Turk J Haematol. 2017;34(4):378-379.

doi: 10.4274/tjh.2017.0234.

Adult patients with mycosis fungoides (MF) have a higher risk of secondary malignancies, according to a 20-year population-based cohort study. The researchers, from Bezmialem Vakif University in Istanbul, Turkey, say their findings support earlier research about a higher risk of, for instance, Hodgkin lymphoma, chronic leukemia, and lung cancer.

Between 1998 and 2015, the researchers documented 143 cases of cutaneous T-cell lymphoma (CTCL). The majority of patients had early-stage disease.

The researchers also documented 13 cases (9%) of secondary malignancy diagnosed at least 3 months after the diagnosis of CTCL. The cancers included bladder cancer, nasopharynx cancer, renal cell carcinoma, lung cancer, and superficial spreading malignant melanoma.

Older age, stage IV disease, lymphomatoid papulosis, and having CTCL for > 10 years raised the chances of developing secondary solid tumors. In 60% of patients, the secondary malignancies occurred during the first year of diagnosis.

Research has suggested that antilymphoma drugs, particularly alkylating agents, may lead to leukemia, the researchers note. In this study, 6 patients with secondary cancers were getting systemic treatment with interferon or acitretin; 7 were getting no systemic treatment.

The researchers add that MF and hematologic malignancies may share genetic origin, carcinogens, or viruses that affect lymphocyte precursors. They also note that the first neoplasm may produce cytokines that induce development of the secondary neoplasm. The researchers cite research that found MF is a T helper cell 2–mediated disease associated with human leukocyte antigen 2 alleles. Viruses such as Epstein-Barr and herpes simplex also have been implicated.

“Extensive evaluation” for secondary malignancies in adult patients with MF is wise, the researchers advise, particularly if the patient has lymphomatoid papulosis.

Source:

Cengiz FP, Emiroğlu N, Onsun N. Turk J Haematol. 2017;34(4):378-379.

doi: 10.4274/tjh.2017.0234.

Advances in the treatment of chronic lymphocytic leukemia (CLL), multiple myeloma, venous thromboembolism (VTE), and acquired thrombotic thrombocytopenic purpura will headline the late-breaking trials session at this year’s annual meeting of the American Society of Hematology in Atlanta.

In a preplanned interim analysis of data from 389 patients in the randomized phase III Murano trial, venetoclax and rituximab therapy proved “superior to the standard of care and well tolerated, and a major advance in the management of [relapsed/refractory] CLL,” ASH President Kenneth C. Anderson, MD said during a premeeting preview session for the media.

In Murano, venetoclax plus rituximab bettered bendamustine plus rituximab in progression-free survival, overall survival, overall and complete response rates, and number of patients achieving minimal residual disease (MRD) negativity, said Dr. Anderson, who is also director of the Lebow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center at Dana-Farber Cancer Institute, Boston.

The results were consistent in all risk subsets, including patients who had high-risk disease by virtue of chromosome 17p deletion, according Dr. Anderson.

In another late-breaking randomized phase III study, known as ALCYONE, adding the CD38-targeting monoclonal antibody daratumumab to standard therapy with bortezomib, melphalan, and prednisone (VMP) resulted in a “doubling” of progression-free survival in patients who had newly diagnosed multiple myeloma and were ineligible for transplantation, he reported.

In the trial of more than 700 patients, daratumumab plus VMP as initial treatment for nontransplant patients was well tolerated and improved outcomes, including overall response rate and the percent of patients who achieved MRD negative status.

“As we saw in CLL, so it’s true in this abstract in myeloma: this is a very major advance,” Dr. Anderson said.

Also during the preview session, ASH Secretary Robert A. Brodsky, MD, discussed the randomized, phase III HERCULES study results, which showed that patients with acquired thrombotic thrombocytopenic purpura (TTP) may benefit when caplacizumab is added to standard therapy. Caplacizumab targets the A1 domain of von Willebrand factor, which inhibits interaction between ultra-large von Willebrand factor and platelets.

In the trial, 145 patients were randomized to receive either plasma exchange alone or plasma exchange and caplacizumab.

Preliminary results suggest “this was a very positive trial” with a primary endpoint of time to platelet response that “greatly favored the caplacizumab arm,” said Dr. Brodsky, professor of medicine and oncology and director of the division of hematology at Johns Hopkins University, Baltimore. “Even the secondary composite endpoint of death, recurrence, and/or major thromboembolic events was much improved with caplacizumab, so this is a very positive trial and potentially a game-changing drug for the management of TTP, which can be very challenging.”

Dr. Brodsky also discussed the Hokusai VTE-Cancer Study, a randomized, open-label, blinded outcome assessment trial that showed the oral factor Xa inhibitor edoxaban was noninferior to subcutaneous dalteparin for the prevention of cancer-associated venous thromboembolism.

With more than 1,000 patients enrolled in 114 centers, the Hokusai VTE-Cancer Study had a primary outcome of the composite of the first recurrent VTE or major bleeding event during follow-up. The primary outcome occurred in 12.8% of patients in the edoxaban group, compared with 13.5% of patients in the dalteparin group (P = .0056 for noninferiority), according to the preliminary published results.

The key question addressed by the trial is whether a newer oral anticoagulant, edoxaban, can substitute for the older, subcutaneously administered low-molecular-weight heparin, dalteparin. The results “confirmed that a newer oral anticoagulant is at least as good and as safe as the low molecular weight heparin,” allowing patients the convenience of an oral therapy, Dr. Brodsky noted.

This year’s late-breaking abstracts at ASH are:

LBA-1 Results of the Randomized, Double-Blind, Placebo-Controlled, Phase III Hercules Study of Caplacizumab in Patients with Acquired Thrombotic Thrombocytopenic Purpura.

LBA-2 Venetoclax Plus Rituximab Is Superior to Bendamustine Plus Rituximab in Patients with Relapsed/ Refractory Chronic Lymphocytic Leukemia - Results from Pre-Planned Interim Analysis of the Randomized Phase III Murano Study.

LBA-3 Mutations in SRP54 Gene Cause Severe Primary Neutropenia As Well As Shwachman-Diamond-like Syndrome.

LBA-4 Phase III Randomized Study of Daratumumab Plus Bortezomib, Melphalan, and Prednisone (D-VMP) Versus Bortezomib, Melphalan, and Prednisone (VMP) in Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts) Ineligible for Transplant (ALCYONE).

LBA-5 Prospective Molecular MRD Detection By NGS: A Powerful Independent Predictor for Relapse and Survival in Adults with Newly Diagnosed AML.

LBA-6 A Randomized, Open-Label, Blinded Outcome Assessment Trial Evaluating the Efficacy and Safety of LMWH/Edoxaban Versus Dalteparin for Venous Thromboembolism Associated with Cancer: Hokusai VTE-Cancer Study

Advances in the treatment of chronic lymphocytic leukemia (CLL), multiple myeloma, venous thromboembolism (VTE), and acquired thrombotic thrombocytopenic purpura will headline the late-breaking trials session at this year’s annual meeting of the American Society of Hematology in Atlanta.

In a preplanned interim analysis of data from 389 patients in the randomized phase III Murano trial, venetoclax and rituximab therapy proved “superior to the standard of care and well tolerated, and a major advance in the management of [relapsed/refractory] CLL,” ASH President Kenneth C. Anderson, MD said during a premeeting preview session for the media.

In Murano, venetoclax plus rituximab bettered bendamustine plus rituximab in progression-free survival, overall survival, overall and complete response rates, and number of patients achieving minimal residual disease (MRD) negativity, said Dr. Anderson, who is also director of the Lebow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center at Dana-Farber Cancer Institute, Boston.

The results were consistent in all risk subsets, including patients who had high-risk disease by virtue of chromosome 17p deletion, according Dr. Anderson.

In another late-breaking randomized phase III study, known as ALCYONE, adding the CD38-targeting monoclonal antibody daratumumab to standard therapy with bortezomib, melphalan, and prednisone (VMP) resulted in a “doubling” of progression-free survival in patients who had newly diagnosed multiple myeloma and were ineligible for transplantation, he reported.

In the trial of more than 700 patients, daratumumab plus VMP as initial treatment for nontransplant patients was well tolerated and improved outcomes, including overall response rate and the percent of patients who achieved MRD negative status.

“As we saw in CLL, so it’s true in this abstract in myeloma: this is a very major advance,” Dr. Anderson said.

Also during the preview session, ASH Secretary Robert A. Brodsky, MD, discussed the randomized, phase III HERCULES study results, which showed that patients with acquired thrombotic thrombocytopenic purpura (TTP) may benefit when caplacizumab is added to standard therapy. Caplacizumab targets the A1 domain of von Willebrand factor, which inhibits interaction between ultra-large von Willebrand factor and platelets.

In the trial, 145 patients were randomized to receive either plasma exchange alone or plasma exchange and caplacizumab.

Preliminary results suggest “this was a very positive trial” with a primary endpoint of time to platelet response that “greatly favored the caplacizumab arm,” said Dr. Brodsky, professor of medicine and oncology and director of the division of hematology at Johns Hopkins University, Baltimore. “Even the secondary composite endpoint of death, recurrence, and/or major thromboembolic events was much improved with caplacizumab, so this is a very positive trial and potentially a game-changing drug for the management of TTP, which can be very challenging.”

Dr. Brodsky also discussed the Hokusai VTE-Cancer Study, a randomized, open-label, blinded outcome assessment trial that showed the oral factor Xa inhibitor edoxaban was noninferior to subcutaneous dalteparin for the prevention of cancer-associated venous thromboembolism.

With more than 1,000 patients enrolled in 114 centers, the Hokusai VTE-Cancer Study had a primary outcome of the composite of the first recurrent VTE or major bleeding event during follow-up. The primary outcome occurred in 12.8% of patients in the edoxaban group, compared with 13.5% of patients in the dalteparin group (P = .0056 for noninferiority), according to the preliminary published results.

The key question addressed by the trial is whether a newer oral anticoagulant, edoxaban, can substitute for the older, subcutaneously administered low-molecular-weight heparin, dalteparin. The results “confirmed that a newer oral anticoagulant is at least as good and as safe as the low molecular weight heparin,” allowing patients the convenience of an oral therapy, Dr. Brodsky noted.

This year’s late-breaking abstracts at ASH are:

LBA-1 Results of the Randomized, Double-Blind, Placebo-Controlled, Phase III Hercules Study of Caplacizumab in Patients with Acquired Thrombotic Thrombocytopenic Purpura.

LBA-2 Venetoclax Plus Rituximab Is Superior to Bendamustine Plus Rituximab in Patients with Relapsed/ Refractory Chronic Lymphocytic Leukemia - Results from Pre-Planned Interim Analysis of the Randomized Phase III Murano Study.

LBA-3 Mutations in SRP54 Gene Cause Severe Primary Neutropenia As Well As Shwachman-Diamond-like Syndrome.

LBA-4 Phase III Randomized Study of Daratumumab Plus Bortezomib, Melphalan, and Prednisone (D-VMP) Versus Bortezomib, Melphalan, and Prednisone (VMP) in Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts) Ineligible for Transplant (ALCYONE).

LBA-5 Prospective Molecular MRD Detection By NGS: A Powerful Independent Predictor for Relapse and Survival in Adults with Newly Diagnosed AML.

LBA-6 A Randomized, Open-Label, Blinded Outcome Assessment Trial Evaluating the Efficacy and Safety of LMWH/Edoxaban Versus Dalteparin for Venous Thromboembolism Associated with Cancer: Hokusai VTE-Cancer Study

Advances in the treatment of chronic lymphocytic leukemia (CLL), multiple myeloma, venous thromboembolism (VTE), and acquired thrombotic thrombocytopenic purpura will headline the late-breaking trials session at this year’s annual meeting of the American Society of Hematology in Atlanta.

In a preplanned interim analysis of data from 389 patients in the randomized phase III Murano trial, venetoclax and rituximab therapy proved “superior to the standard of care and well tolerated, and a major advance in the management of [relapsed/refractory] CLL,” ASH President Kenneth C. Anderson, MD said during a premeeting preview session for the media.

In Murano, venetoclax plus rituximab bettered bendamustine plus rituximab in progression-free survival, overall survival, overall and complete response rates, and number of patients achieving minimal residual disease (MRD) negativity, said Dr. Anderson, who is also director of the Lebow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center at Dana-Farber Cancer Institute, Boston.

The results were consistent in all risk subsets, including patients who had high-risk disease by virtue of chromosome 17p deletion, according Dr. Anderson.

In another late-breaking randomized phase III study, known as ALCYONE, adding the CD38-targeting monoclonal antibody daratumumab to standard therapy with bortezomib, melphalan, and prednisone (VMP) resulted in a “doubling” of progression-free survival in patients who had newly diagnosed multiple myeloma and were ineligible for transplantation, he reported.

In the trial of more than 700 patients, daratumumab plus VMP as initial treatment for nontransplant patients was well tolerated and improved outcomes, including overall response rate and the percent of patients who achieved MRD negative status.

“As we saw in CLL, so it’s true in this abstract in myeloma: this is a very major advance,” Dr. Anderson said.

Also during the preview session, ASH Secretary Robert A. Brodsky, MD, discussed the randomized, phase III HERCULES study results, which showed that patients with acquired thrombotic thrombocytopenic purpura (TTP) may benefit when caplacizumab is added to standard therapy. Caplacizumab targets the A1 domain of von Willebrand factor, which inhibits interaction between ultra-large von Willebrand factor and platelets.

In the trial, 145 patients were randomized to receive either plasma exchange alone or plasma exchange and caplacizumab.

Preliminary results suggest “this was a very positive trial” with a primary endpoint of time to platelet response that “greatly favored the caplacizumab arm,” said Dr. Brodsky, professor of medicine and oncology and director of the division of hematology at Johns Hopkins University, Baltimore. “Even the secondary composite endpoint of death, recurrence, and/or major thromboembolic events was much improved with caplacizumab, so this is a very positive trial and potentially a game-changing drug for the management of TTP, which can be very challenging.”

Dr. Brodsky also discussed the Hokusai VTE-Cancer Study, a randomized, open-label, blinded outcome assessment trial that showed the oral factor Xa inhibitor edoxaban was noninferior to subcutaneous dalteparin for the prevention of cancer-associated venous thromboembolism.

With more than 1,000 patients enrolled in 114 centers, the Hokusai VTE-Cancer Study had a primary outcome of the composite of the first recurrent VTE or major bleeding event during follow-up. The primary outcome occurred in 12.8% of patients in the edoxaban group, compared with 13.5% of patients in the dalteparin group (P = .0056 for noninferiority), according to the preliminary published results.

The key question addressed by the trial is whether a newer oral anticoagulant, edoxaban, can substitute for the older, subcutaneously administered low-molecular-weight heparin, dalteparin. The results “confirmed that a newer oral anticoagulant is at least as good and as safe as the low molecular weight heparin,” allowing patients the convenience of an oral therapy, Dr. Brodsky noted.

This year’s late-breaking abstracts at ASH are:

LBA-1 Results of the Randomized, Double-Blind, Placebo-Controlled, Phase III Hercules Study of Caplacizumab in Patients with Acquired Thrombotic Thrombocytopenic Purpura.

LBA-2 Venetoclax Plus Rituximab Is Superior to Bendamustine Plus Rituximab in Patients with Relapsed/ Refractory Chronic Lymphocytic Leukemia - Results from Pre-Planned Interim Analysis of the Randomized Phase III Murano Study.

LBA-3 Mutations in SRP54 Gene Cause Severe Primary Neutropenia As Well As Shwachman-Diamond-like Syndrome.

LBA-4 Phase III Randomized Study of Daratumumab Plus Bortezomib, Melphalan, and Prednisone (D-VMP) Versus Bortezomib, Melphalan, and Prednisone (VMP) in Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts) Ineligible for Transplant (ALCYONE).

LBA-5 Prospective Molecular MRD Detection By NGS: A Powerful Independent Predictor for Relapse and Survival in Adults with Newly Diagnosed AML.

LBA-6 A Randomized, Open-Label, Blinded Outcome Assessment Trial Evaluating the Efficacy and Safety of LMWH/Edoxaban Versus Dalteparin for Venous Thromboembolism Associated with Cancer: Hokusai VTE-Cancer Study

Overweight and obesity are associated with an increased risk of 13 types of cancer—and those cancers account for about 40% of all cancers diagnosed in 2014, according to the CDC.

The 13 cancers are meningioma, adenocarcinoma of the esophagus, multiple myeloma, kidney, uterine, ovarian, thyroid, breast, liver, gallbladder, upper stomach, pancreas, and colorectal. About 630,000 people were diagnosed with 1 of those cancers in 2014; 2 in 3 cancers were in adults aged 50 to 74 years. In 2013-2014, about 2 of every 3 American adults were overweight or obese.

Related: The Impact of Obesity on Simvastatin for Lowering LDL-C Among Veterans

Overall, the rate of new cancer cases has been on the decline since the 1990s, the report says, but increases in overweight- and obesity-related cancers “are likely slowing this progress.” Obesity-related cancers (not including colorectal cancer, which declined by 23%) increased by 7% between 2005 and 2014, while the rates of nonobesity–related cancers declined 13%.  

Health care providers can help, the CDC says, by counseling patients on healthy weight and its role in cancer prevention, referring obese patients to intensive management programs and connecting patients and their families to community services that give them easier access to healthful food. The National Comprehensive Cancer Control Program (https://www.cdc.gov/cancer/ncccp/index.htm) funds cancer coalitions across the U.S., which include strategies to prevent and control overweight and obesity.

Related: The Impact of Obesity on the Recovery of Patients With Cancer

“When people ask me if there’s a cure for cancer, I say, ‘Yes, good health is the best prescription for preventing chronic diseases, including cancer,” said Lisa Richardson, MD, director of CDC’s Division of Cancer Prevention and Control. That means, she says, giving people the information they need to make healthy choices where they live, work, learn, and play.

Overweight and obesity are associated with an increased risk of 13 types of cancer—and those cancers account for about 40% of all cancers diagnosed in 2014, according to the CDC.

The 13 cancers are meningioma, adenocarcinoma of the esophagus, multiple myeloma, kidney, uterine, ovarian, thyroid, breast, liver, gallbladder, upper stomach, pancreas, and colorectal. About 630,000 people were diagnosed with 1 of those cancers in 2014; 2 in 3 cancers were in adults aged 50 to 74 years. In 2013-2014, about 2 of every 3 American adults were overweight or obese.

Related: The Impact of Obesity on Simvastatin for Lowering LDL-C Among Veterans

Overall, the rate of new cancer cases has been on the decline since the 1990s, the report says, but increases in overweight- and obesity-related cancers “are likely slowing this progress.” Obesity-related cancers (not including colorectal cancer, which declined by 23%) increased by 7% between 2005 and 2014, while the rates of nonobesity–related cancers declined 13%.  

Health care providers can help, the CDC says, by counseling patients on healthy weight and its role in cancer prevention, referring obese patients to intensive management programs and connecting patients and their families to community services that give them easier access to healthful food. The National Comprehensive Cancer Control Program (https://www.cdc.gov/cancer/ncccp/index.htm) funds cancer coalitions across the U.S., which include strategies to prevent and control overweight and obesity.

Related: The Impact of Obesity on the Recovery of Patients With Cancer

“When people ask me if there’s a cure for cancer, I say, ‘Yes, good health is the best prescription for preventing chronic diseases, including cancer,” said Lisa Richardson, MD, director of CDC’s Division of Cancer Prevention and Control. That means, she says, giving people the information they need to make healthy choices where they live, work, learn, and play.

Overweight and obesity are associated with an increased risk of 13 types of cancer—and those cancers account for about 40% of all cancers diagnosed in 2014, according to the CDC.

The 13 cancers are meningioma, adenocarcinoma of the esophagus, multiple myeloma, kidney, uterine, ovarian, thyroid, breast, liver, gallbladder, upper stomach, pancreas, and colorectal. About 630,000 people were diagnosed with 1 of those cancers in 2014; 2 in 3 cancers were in adults aged 50 to 74 years. In 2013-2014, about 2 of every 3 American adults were overweight or obese.

Related: The Impact of Obesity on Simvastatin for Lowering LDL-C Among Veterans

Overall, the rate of new cancer cases has been on the decline since the 1990s, the report says, but increases in overweight- and obesity-related cancers “are likely slowing this progress.” Obesity-related cancers (not including colorectal cancer, which declined by 23%) increased by 7% between 2005 and 2014, while the rates of nonobesity–related cancers declined 13%.  

Health care providers can help, the CDC says, by counseling patients on healthy weight and its role in cancer prevention, referring obese patients to intensive management programs and connecting patients and their families to community services that give them easier access to healthful food. The National Comprehensive Cancer Control Program (https://www.cdc.gov/cancer/ncccp/index.htm) funds cancer coalitions across the U.S., which include strategies to prevent and control overweight and obesity.

Related: The Impact of Obesity on the Recovery of Patients With Cancer

“When people ask me if there’s a cure for cancer, I say, ‘Yes, good health is the best prescription for preventing chronic diseases, including cancer,” said Lisa Richardson, MD, director of CDC’s Division of Cancer Prevention and Control. That means, she says, giving people the information they need to make healthy choices where they live, work, learn, and play.

A 40-year-old man suddenly began to lose vision in his left eye. The retinal exam was normal for the right eye. But the left showed isolated subinternal limited membrane hemorrhage at the fovea along with a white-centered hemorrhage above the fovea.

The patient had no history of trauma or Valsalva retinopathy. His blood pressure was normal as was his blood glucose. However, when bloodwork showed a high total count, increased platelet count, and the peripheral smear indicated myeloid hyperplasia, clinicians at LV Prasad Eye Institute in Hyderabad, India, diagnosed the patient with underlying chronic myeloid leukemia (CML).  

A physical examination revealed a palpable spleenomegaly—underscoring the fact, the clinicians note, that when an ophthalmologic finding suggests a systemic disease, a general physical examination will reveal more clinical clues. The patient was referred to an oncologist and started on imatinib for CML.

White-centered or pale-centered hemorrhages are believed to represent an accumulation of leukemic cells or platelet fibrin aggregates, the clinicians say. Blood dyscrasias, such as anemias, leukemia, multiple myeloma, and other platelet disorders may present with similar features. Such hemorrhages are known to resolve spontaneously when the patient is treated for the underlying condition, and the hematologic status improves, the clinicians say. This patient’s hemorrhage gradually resolved over the next month, and his visual acuity improved to 20/20.

Ocular manifestations as a presenting sign of leukemia, especially chronic, are rare, the clinicians say. They note that retinal hemorrhages are one of the “most striking findings” in leukemia, and because they can be directly observed, they provide a “subtle but important clue toward an otherwise asymptomatic disease.” If diagnosed early and treated promptly, patients with CML have a good survival rate.

Source:

Tyagi M, Agarwal K, Paulose RM, Rani PK. BMJ Case Rep. 2017;2017: pii: bcr-2017-21974.

doi: 10.1136/bcr-2017-219741.

A 40-year-old man suddenly began to lose vision in his left eye. The retinal exam was normal for the right eye. But the left showed isolated subinternal limited membrane hemorrhage at the fovea along with a white-centered hemorrhage above the fovea.

The patient had no history of trauma or Valsalva retinopathy. His blood pressure was normal as was his blood glucose. However, when bloodwork showed a high total count, increased platelet count, and the peripheral smear indicated myeloid hyperplasia, clinicians at LV Prasad Eye Institute in Hyderabad, India, diagnosed the patient with underlying chronic myeloid leukemia (CML).  

A physical examination revealed a palpable spleenomegaly—underscoring the fact, the clinicians note, that when an ophthalmologic finding suggests a systemic disease, a general physical examination will reveal more clinical clues. The patient was referred to an oncologist and started on imatinib for CML.

White-centered or pale-centered hemorrhages are believed to represent an accumulation of leukemic cells or platelet fibrin aggregates, the clinicians say. Blood dyscrasias, such as anemias, leukemia, multiple myeloma, and other platelet disorders may present with similar features. Such hemorrhages are known to resolve spontaneously when the patient is treated for the underlying condition, and the hematologic status improves, the clinicians say. This patient’s hemorrhage gradually resolved over the next month, and his visual acuity improved to 20/20.

Ocular manifestations as a presenting sign of leukemia, especially chronic, are rare, the clinicians say. They note that retinal hemorrhages are one of the “most striking findings” in leukemia, and because they can be directly observed, they provide a “subtle but important clue toward an otherwise asymptomatic disease.” If diagnosed early and treated promptly, patients with CML have a good survival rate.

Source:

Tyagi M, Agarwal K, Paulose RM, Rani PK. BMJ Case Rep. 2017;2017: pii: bcr-2017-21974.

doi: 10.1136/bcr-2017-219741.

A 40-year-old man suddenly began to lose vision in his left eye. The retinal exam was normal for the right eye. But the left showed isolated subinternal limited membrane hemorrhage at the fovea along with a white-centered hemorrhage above the fovea.

The patient had no history of trauma or Valsalva retinopathy. His blood pressure was normal as was his blood glucose. However, when bloodwork showed a high total count, increased platelet count, and the peripheral smear indicated myeloid hyperplasia, clinicians at LV Prasad Eye Institute in Hyderabad, India, diagnosed the patient with underlying chronic myeloid leukemia (CML).  

A physical examination revealed a palpable spleenomegaly—underscoring the fact, the clinicians note, that when an ophthalmologic finding suggests a systemic disease, a general physical examination will reveal more clinical clues. The patient was referred to an oncologist and started on imatinib for CML.

White-centered or pale-centered hemorrhages are believed to represent an accumulation of leukemic cells or platelet fibrin aggregates, the clinicians say. Blood dyscrasias, such as anemias, leukemia, multiple myeloma, and other platelet disorders may present with similar features. Such hemorrhages are known to resolve spontaneously when the patient is treated for the underlying condition, and the hematologic status improves, the clinicians say. This patient’s hemorrhage gradually resolved over the next month, and his visual acuity improved to 20/20.

Ocular manifestations as a presenting sign of leukemia, especially chronic, are rare, the clinicians say. They note that retinal hemorrhages are one of the “most striking findings” in leukemia, and because they can be directly observed, they provide a “subtle but important clue toward an otherwise asymptomatic disease.” If diagnosed early and treated promptly, patients with CML have a good survival rate.

Source:

Tyagi M, Agarwal K, Paulose RM, Rani PK. BMJ Case Rep. 2017;2017: pii: bcr-2017-21974.

doi: 10.1136/bcr-2017-219741.

A rare type of mantle cell lymphoma (MCL) has features that are similar to those of Castleman disease, according to a recent report based on three patient cases.

Lymph node biopsies for these patients initially indicated histologic features consistent with those of plasma cell (PC)-type Castleman disease, reported Takuro Igawa, MD, PhD, of Okayama (Japan) University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, and his coauthors. Further work-up, including flow cytometric analysis and cyclin D1 immunostaining, showed features consistent with those of MCL.

“This rare type of MCL can mimic Castleman disease in the clinical setting and upon histological examination,” Dr. Igawa and his colleagues wrote (Pathol Res Pract. 2017 Sep 18. pii: S0344-0338[17]30684-2. doi: 10.1016/j.prp.2017.09.015). “These confusing characteristics can make the diagnosis challenging, and careful flow cytometric analysis is recommended when a histopathological diagnosis is made.”

The patients in the study, all male, were 51, 74, and 81 years of age. Each presented with systemic lymphadenopathy, along with abnormal laboratory findings that according to the investigators are not usually associated with B-cell lymphomas such as MCL, including anemia, polyclonal IgG hypergammaglobulinemia, and elevated levels of C-reactive protein.

In lymph node biopsy specimens, the MCL component was “masked by histological features of PC-type Castleman disease” such as interfollicular plasmacytosis and atrophic germinal centers, the researchers wrote.

However, further pathologic investigations revealed features that were “essential to distinguish these 3 cases of MCL from PC-type Castleman disease,” they added.

In particular, an abnormal B-cell population was found using flow cytometric analysis, while subsequent cyclin D1 immunostaining in all three cases showed abnormal B-cells primarily in the mantle zone that were positive for CD20 and CD5, both typically expressed by MCL, along with SOX11, which is an “excellent diagnostic marker for MCL, including atypical MCL,” the investigators wrote.

These case reports also provide some evidence that interleukin-6 (IL-6), which is thought to be a driver of Castleman disease, might also be implicated in the pathogenesis of this rare MCL variant. the researchers found that all three cases had positive IL-6 staining in the interfollicular areas.

If further studies confirm the role of IL-6 in this rare setting, “specific treatments other than chemotherapy could potentially be used for patients with MCL with features of Castleman disease, such as an anti-IL-6 receptor antibody (tocilizumab), which is already used for patients with Castleman disease,” they said.

A rare type of mantle cell lymphoma (MCL) has features that are similar to those of Castleman disease, according to a recent report based on three patient cases.

Lymph node biopsies for these patients initially indicated histologic features consistent with those of plasma cell (PC)-type Castleman disease, reported Takuro Igawa, MD, PhD, of Okayama (Japan) University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, and his coauthors. Further work-up, including flow cytometric analysis and cyclin D1 immunostaining, showed features consistent with those of MCL.

“This rare type of MCL can mimic Castleman disease in the clinical setting and upon histological examination,” Dr. Igawa and his colleagues wrote (Pathol Res Pract. 2017 Sep 18. pii: S0344-0338[17]30684-2. doi: 10.1016/j.prp.2017.09.015). “These confusing characteristics can make the diagnosis challenging, and careful flow cytometric analysis is recommended when a histopathological diagnosis is made.”

The patients in the study, all male, were 51, 74, and 81 years of age. Each presented with systemic lymphadenopathy, along with abnormal laboratory findings that according to the investigators are not usually associated with B-cell lymphomas such as MCL, including anemia, polyclonal IgG hypergammaglobulinemia, and elevated levels of C-reactive protein.

In lymph node biopsy specimens, the MCL component was “masked by histological features of PC-type Castleman disease” such as interfollicular plasmacytosis and atrophic germinal centers, the researchers wrote.

However, further pathologic investigations revealed features that were “essential to distinguish these 3 cases of MCL from PC-type Castleman disease,” they added.

In particular, an abnormal B-cell population was found using flow cytometric analysis, while subsequent cyclin D1 immunostaining in all three cases showed abnormal B-cells primarily in the mantle zone that were positive for CD20 and CD5, both typically expressed by MCL, along with SOX11, which is an “excellent diagnostic marker for MCL, including atypical MCL,” the investigators wrote.

These case reports also provide some evidence that interleukin-6 (IL-6), which is thought to be a driver of Castleman disease, might also be implicated in the pathogenesis of this rare MCL variant. the researchers found that all three cases had positive IL-6 staining in the interfollicular areas.

If further studies confirm the role of IL-6 in this rare setting, “specific treatments other than chemotherapy could potentially be used for patients with MCL with features of Castleman disease, such as an anti-IL-6 receptor antibody (tocilizumab), which is already used for patients with Castleman disease,” they said.

A rare type of mantle cell lymphoma (MCL) has features that are similar to those of Castleman disease, according to a recent report based on three patient cases.

Lymph node biopsies for these patients initially indicated histologic features consistent with those of plasma cell (PC)-type Castleman disease, reported Takuro Igawa, MD, PhD, of Okayama (Japan) University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, and his coauthors. Further work-up, including flow cytometric analysis and cyclin D1 immunostaining, showed features consistent with those of MCL.

“This rare type of MCL can mimic Castleman disease in the clinical setting and upon histological examination,” Dr. Igawa and his colleagues wrote (Pathol Res Pract. 2017 Sep 18. pii: S0344-0338[17]30684-2. doi: 10.1016/j.prp.2017.09.015). “These confusing characteristics can make the diagnosis challenging, and careful flow cytometric analysis is recommended when a histopathological diagnosis is made.”

The patients in the study, all male, were 51, 74, and 81 years of age. Each presented with systemic lymphadenopathy, along with abnormal laboratory findings that according to the investigators are not usually associated with B-cell lymphomas such as MCL, including anemia, polyclonal IgG hypergammaglobulinemia, and elevated levels of C-reactive protein.

In lymph node biopsy specimens, the MCL component was “masked by histological features of PC-type Castleman disease” such as interfollicular plasmacytosis and atrophic germinal centers, the researchers wrote.

However, further pathologic investigations revealed features that were “essential to distinguish these 3 cases of MCL from PC-type Castleman disease,” they added.

In particular, an abnormal B-cell population was found using flow cytometric analysis, while subsequent cyclin D1 immunostaining in all three cases showed abnormal B-cells primarily in the mantle zone that were positive for CD20 and CD5, both typically expressed by MCL, along with SOX11, which is an “excellent diagnostic marker for MCL, including atypical MCL,” the investigators wrote.

These case reports also provide some evidence that interleukin-6 (IL-6), which is thought to be a driver of Castleman disease, might also be implicated in the pathogenesis of this rare MCL variant. the researchers found that all three cases had positive IL-6 staining in the interfollicular areas.

If further studies confirm the role of IL-6 in this rare setting, “specific treatments other than chemotherapy could potentially be used for patients with MCL with features of Castleman disease, such as an anti-IL-6 receptor antibody (tocilizumab), which is already used for patients with Castleman disease,” they said.

A treatment for cancer is finding a new purpose in treating another life-threatening condition. The FDA expanded approval of Ibrutinib for treatment of adults with chronic graft versus host disease (cGVHD) after ≥ 1 treatments have failed. Ibrutinib was previously approved for certain indications in treating chronic lymphocytic leukemia, Waldenström macroglobulinemia, and marginal zone lymphoma.

An estimated 30% to 70% of patients who receive hematopoietic stem cell transplantation for blood or bone marrow cancer develop cGVHD.

Ibrutinib , a kinase inhibitor, was tested in a single-arm trial of 42 patients with cGVHD. Most had mouth ulcers and skin rashes; > 50% had ≥ 2 organs affected. Their symptoms had persisted despite standard treatment with corticosteroids. In the study, cGVHD symptoms improved in 67%. For nearly half (48%), the improvements lasted for 5 months or longer.

Common adverse effects include fatigue, bruising, diarrhea, and thrombocytopenia. Serious adverse effects include severe bleeding, infections, and cytopenia.

A treatment for cancer is finding a new purpose in treating another life-threatening condition. The FDA expanded approval of Ibrutinib for treatment of adults with chronic graft versus host disease (cGVHD) after ≥ 1 treatments have failed. Ibrutinib was previously approved for certain indications in treating chronic lymphocytic leukemia, Waldenström macroglobulinemia, and marginal zone lymphoma.

An estimated 30% to 70% of patients who receive hematopoietic stem cell transplantation for blood or bone marrow cancer develop cGVHD.

Ibrutinib , a kinase inhibitor, was tested in a single-arm trial of 42 patients with cGVHD. Most had mouth ulcers and skin rashes; > 50% had ≥ 2 organs affected. Their symptoms had persisted despite standard treatment with corticosteroids. In the study, cGVHD symptoms improved in 67%. For nearly half (48%), the improvements lasted for 5 months or longer.

Common adverse effects include fatigue, bruising, diarrhea, and thrombocytopenia. Serious adverse effects include severe bleeding, infections, and cytopenia.

A treatment for cancer is finding a new purpose in treating another life-threatening condition. The FDA expanded approval of Ibrutinib for treatment of adults with chronic graft versus host disease (cGVHD) after ≥ 1 treatments have failed. Ibrutinib was previously approved for certain indications in treating chronic lymphocytic leukemia, Waldenström macroglobulinemia, and marginal zone lymphoma.

An estimated 30% to 70% of patients who receive hematopoietic stem cell transplantation for blood or bone marrow cancer develop cGVHD.

Ibrutinib , a kinase inhibitor, was tested in a single-arm trial of 42 patients with cGVHD. Most had mouth ulcers and skin rashes; > 50% had ≥ 2 organs affected. Their symptoms had persisted despite standard treatment with corticosteroids. In the study, cGVHD symptoms improved in 67%. For nearly half (48%), the improvements lasted for 5 months or longer.

Common adverse effects include fatigue, bruising, diarrhea, and thrombocytopenia. Serious adverse effects include severe bleeding, infections, and cytopenia.

After stem cell therapy, profiles may show a pattern of antibodies that can look very much like the “M spike”—the signature of the monoclonal antibody produced by multiple myeloma (MM). But that pattern, called an oligoclonal band, can be misleading.

“Oligoclonal bands should mostly be recognized as a response to treatment and not be mistaken as a recurrence of the original tumor,” says Dr. Gurmukh Singh, vice chair of clinical affairs for the Department of Pathology at the Medical College of Georgia at Augusta University.

He and his research team analyzed data from 251 patients with MM, 159 of whom had received autologous stem cell transplants. The researchers performed tests using serum protein electrophoresis/serum immunofixation electrophoresis and serum free light chain assay. Each patient had at least 3 tests, with at least 2 following the transplant.

The researchers found the incidence of oligoclonal patterns was dramatically higher in patients who had a stem cell transplant, compared with patients who had chemotherapy alone (57.9% vs 8.8%). Moreover, only 5 of the 159 patients who received a transplant had an oligoclonal pattern before treatment, but 92 had 1 afterward. More than half the oligoclonal patterns developed within the first year following transplant. The earliest pattern was detected at 2 months and a few as long as 5 years later.

The key to assessing response, Singh says, is to see where the spike appears: that is, where the monoclonal spike is at diagnosis compared with any new spikes that appear in oligoclonal bands after stem cell treatment. “If the original peak was at location A, [and] now the peak is location B, that allows us to determine that it is not the same abnormal, malignant antibody.”

The finding that 58% of patients had the oligoclonal pattern after transplant is likely an underestimate due to irregular schedule of testing, the researchers say. They add that their findings highlight the need for higher resolution electrophoretic methods to obviate the need for using mass spectrometry for clinical samples. Their results “cast more doubt on the clinical usefulness and medical necessity of the serum free light chain assay.”

Source:

Baker T. Results after stem cell transplant can confuse patients and doctors about cancer’s status. Jagwire News. https://jagwire.augusta.edu/archives/46434. Published August 2017. Accessed September 20, 2017.

Singh G. J Clin Med Res. 2017;9(8):671-679.
doi:  10.14740/jocmr3049w.

After stem cell therapy, profiles may show a pattern of antibodies that can look very much like the “M spike”—the signature of the monoclonal antibody produced by multiple myeloma (MM). But that pattern, called an oligoclonal band, can be misleading.

“Oligoclonal bands should mostly be recognized as a response to treatment and not be mistaken as a recurrence of the original tumor,” says Dr. Gurmukh Singh, vice chair of clinical affairs for the Department of Pathology at the Medical College of Georgia at Augusta University.

He and his research team analyzed data from 251 patients with MM, 159 of whom had received autologous stem cell transplants. The researchers performed tests using serum protein electrophoresis/serum immunofixation electrophoresis and serum free light chain assay. Each patient had at least 3 tests, with at least 2 following the transplant.

The researchers found the incidence of oligoclonal patterns was dramatically higher in patients who had a stem cell transplant, compared with patients who had chemotherapy alone (57.9% vs 8.8%). Moreover, only 5 of the 159 patients who received a transplant had an oligoclonal pattern before treatment, but 92 had 1 afterward. More than half the oligoclonal patterns developed within the first year following transplant. The earliest pattern was detected at 2 months and a few as long as 5 years later.

The key to assessing response, Singh says, is to see where the spike appears: that is, where the monoclonal spike is at diagnosis compared with any new spikes that appear in oligoclonal bands after stem cell treatment. “If the original peak was at location A, [and] now the peak is location B, that allows us to determine that it is not the same abnormal, malignant antibody.”

The finding that 58% of patients had the oligoclonal pattern after transplant is likely an underestimate due to irregular schedule of testing, the researchers say. They add that their findings highlight the need for higher resolution electrophoretic methods to obviate the need for using mass spectrometry for clinical samples. Their results “cast more doubt on the clinical usefulness and medical necessity of the serum free light chain assay.”

Source:

Baker T. Results after stem cell transplant can confuse patients and doctors about cancer’s status. Jagwire News. https://jagwire.augusta.edu/archives/46434. Published August 2017. Accessed September 20, 2017.

Singh G. J Clin Med Res. 2017;9(8):671-679.
doi:  10.14740/jocmr3049w.

After stem cell therapy, profiles may show a pattern of antibodies that can look very much like the “M spike”—the signature of the monoclonal antibody produced by multiple myeloma (MM). But that pattern, called an oligoclonal band, can be misleading.

“Oligoclonal bands should mostly be recognized as a response to treatment and not be mistaken as a recurrence of the original tumor,” says Dr. Gurmukh Singh, vice chair of clinical affairs for the Department of Pathology at the Medical College of Georgia at Augusta University.

He and his research team analyzed data from 251 patients with MM, 159 of whom had received autologous stem cell transplants. The researchers performed tests using serum protein electrophoresis/serum immunofixation electrophoresis and serum free light chain assay. Each patient had at least 3 tests, with at least 2 following the transplant.

The researchers found the incidence of oligoclonal patterns was dramatically higher in patients who had a stem cell transplant, compared with patients who had chemotherapy alone (57.9% vs 8.8%). Moreover, only 5 of the 159 patients who received a transplant had an oligoclonal pattern before treatment, but 92 had 1 afterward. More than half the oligoclonal patterns developed within the first year following transplant. The earliest pattern was detected at 2 months and a few as long as 5 years later.

The key to assessing response, Singh says, is to see where the spike appears: that is, where the monoclonal spike is at diagnosis compared with any new spikes that appear in oligoclonal bands after stem cell treatment. “If the original peak was at location A, [and] now the peak is location B, that allows us to determine that it is not the same abnormal, malignant antibody.”

The finding that 58% of patients had the oligoclonal pattern after transplant is likely an underestimate due to irregular schedule of testing, the researchers say. They add that their findings highlight the need for higher resolution electrophoretic methods to obviate the need for using mass spectrometry for clinical samples. Their results “cast more doubt on the clinical usefulness and medical necessity of the serum free light chain assay.”

Source:

Baker T. Results after stem cell transplant can confuse patients and doctors about cancer’s status. Jagwire News. https://jagwire.augusta.edu/archives/46434. Published August 2017. Accessed September 20, 2017.

Singh G. J Clin Med Res. 2017;9(8):671-679.
doi:  10.14740/jocmr3049w.

The FDA has approved Besponsa (inotuzumab ozogamicin) for adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL), a rapidly progressing cancer affecting about 6,000 people each year. About 1 in 4 patients affected will die of the disease. 

Inotuzumab ozogamicin is a targeted therapy “thought to work” by binding to B-cell ALL cancer cells that express the CD22 antigen, blocking the growth of cancerous cells. In a study of 326 patients with relapsed or refractory B-cell ALL who had received 1 or 2 prior treatments, 36% of 218 evaluated patients experienced complete remission for a median 8 months. Of the patients who received alternative chemotherapy, 17% experienced complete remission for a median 5 months.

A second drug, Vyxeos ( daunorubicin and cytarabine) liposome injection, is approved for adults with 2 types of acute myeloid leukemia (AML): newly diagnosed therapy-related AML (t-AML) or AML with myelodysplasia-related changes (AML-MRC).

An estimated 8% to 10% of patients with AML develop t-AML as a complication of chemotherapy or radiation. AML-MRC is characterized by a history of certain blood disorders and other significant mutations within cancer cells. Patients with either disease have a low life expectancy. Vyxeos is a fixed-combination of daunorubicin and cytarabine. It’s the first approved treatment specifically for these patients, says Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence.

In a study of 309 patients with newly diagnosed t-AML or AML-MRC, those in the Vyxeos group lived longer: median survival, 9.56 months vs. 5.95 months in the patients who received separate treatments with daunorubicin and cytarabine.The third drug, Idhifa (enasidenib), is approved for adults with relapsed or refractory AML who have a mutation in the IDH2 gene. Idhifa is an isocitrate dehydrogenase-2 inhibitor that blocks several enzymes that promote cell growth.

The drug was studied in a single-arm trial of 199 patients. With a minimum of 6 months of treatment, 19% of patients experienced complete remission for a median of 8.2 months; 4% experienced complete remission with partial hematologic recovery for a median 9.6 months. Of the 157 patients who required blood or platelet transfusions due to AML at the start of the study, 34% no longer did after treatment with Idhifa.

Idhifa is approved for use with a companion diagnostic, the RealTime IDH2 Assay, which is used to detect mutations in the IDH2 gene in blood or bone marrow.

Source:

FDA approves new treatment for adults with relapsed or refractory acute lymphoblastic leukemia [news release]. Silver Spring, MD: U.S. Food & Drug Administration; August 17,2017. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm572131.htm. Accessed August 31, 2017.

FDA approves new targeted treatment for relapsed or refractory acute myeloid leukemia [news release]. Silver Spring, MD: U.S. Food & Drug Administration; August 1, 2017. https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm569421.htm. Accessed August 31, 2017.

FDA approves first treatment for certain types of poor-prognosis acute myeloid leukemia [news release]. Silver Spring, MD: U.S. Food & Drug Administration; August 3, 2017. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm569883.htm. Accessed August 31, 2017.

The FDA has approved Besponsa (inotuzumab ozogamicin) for adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL), a rapidly progressing cancer affecting about 6,000 people each year. About 1 in 4 patients affected will die of the disease. 

Inotuzumab ozogamicin is a targeted therapy “thought to work” by binding to B-cell ALL cancer cells that express the CD22 antigen, blocking the growth of cancerous cells. In a study of 326 patients with relapsed or refractory B-cell ALL who had received 1 or 2 prior treatments, 36% of 218 evaluated patients experienced complete remission for a median 8 months. Of the patients who received alternative chemotherapy, 17% experienced complete remission for a median 5 months.

A second drug, Vyxeos ( daunorubicin and cytarabine) liposome injection, is approved for adults with 2 types of acute myeloid leukemia (AML): newly diagnosed therapy-related AML (t-AML) or AML with myelodysplasia-related changes (AML-MRC).

An estimated 8% to 10% of patients with AML develop t-AML as a complication of chemotherapy or radiation. AML-MRC is characterized by a history of certain blood disorders and other significant mutations within cancer cells. Patients with either disease have a low life expectancy. Vyxeos is a fixed-combination of daunorubicin and cytarabine. It’s the first approved treatment specifically for these patients, says Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence.

In a study of 309 patients with newly diagnosed t-AML or AML-MRC, those in the Vyxeos group lived longer: median survival, 9.56 months vs. 5.95 months in the patients who received separate treatments with daunorubicin and cytarabine.The third drug, Idhifa (enasidenib), is approved for adults with relapsed or refractory AML who have a mutation in the IDH2 gene. Idhifa is an isocitrate dehydrogenase-2 inhibitor that blocks several enzymes that promote cell growth.

The drug was studied in a single-arm trial of 199 patients. With a minimum of 6 months of treatment, 19% of patients experienced complete remission for a median of 8.2 months; 4% experienced complete remission with partial hematologic recovery for a median 9.6 months. Of the 157 patients who required blood or platelet transfusions due to AML at the start of the study, 34% no longer did after treatment with Idhifa.

Idhifa is approved for use with a companion diagnostic, the RealTime IDH2 Assay, which is used to detect mutations in the IDH2 gene in blood or bone marrow.

Source:

FDA approves new treatment for adults with relapsed or refractory acute lymphoblastic leukemia [news release]. Silver Spring, MD: U.S. Food & Drug Administration; August 17,2017. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm572131.htm. Accessed August 31, 2017.

FDA approves new targeted treatment for relapsed or refractory acute myeloid leukemia [news release]. Silver Spring, MD: U.S. Food & Drug Administration; August 1, 2017. https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm569421.htm. Accessed August 31, 2017.

FDA approves first treatment for certain types of poor-prognosis acute myeloid leukemia [news release]. Silver Spring, MD: U.S. Food & Drug Administration; August 3, 2017. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm569883.htm. Accessed August 31, 2017.

The FDA has approved Besponsa (inotuzumab ozogamicin) for adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL), a rapidly progressing cancer affecting about 6,000 people each year. About 1 in 4 patients affected will die of the disease. 

Inotuzumab ozogamicin is a targeted therapy “thought to work” by binding to B-cell ALL cancer cells that express the CD22 antigen, blocking the growth of cancerous cells. In a study of 326 patients with relapsed or refractory B-cell ALL who had received 1 or 2 prior treatments, 36% of 218 evaluated patients experienced complete remission for a median 8 months. Of the patients who received alternative chemotherapy, 17% experienced complete remission for a median 5 months.

A second drug, Vyxeos ( daunorubicin and cytarabine) liposome injection, is approved for adults with 2 types of acute myeloid leukemia (AML): newly diagnosed therapy-related AML (t-AML) or AML with myelodysplasia-related changes (AML-MRC).

An estimated 8% to 10% of patients with AML develop t-AML as a complication of chemotherapy or radiation. AML-MRC is characterized by a history of certain blood disorders and other significant mutations within cancer cells. Patients with either disease have a low life expectancy. Vyxeos is a fixed-combination of daunorubicin and cytarabine. It’s the first approved treatment specifically for these patients, says Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence.

In a study of 309 patients with newly diagnosed t-AML or AML-MRC, those in the Vyxeos group lived longer: median survival, 9.56 months vs. 5.95 months in the patients who received separate treatments with daunorubicin and cytarabine.The third drug, Idhifa (enasidenib), is approved for adults with relapsed or refractory AML who have a mutation in the IDH2 gene. Idhifa is an isocitrate dehydrogenase-2 inhibitor that blocks several enzymes that promote cell growth.

The drug was studied in a single-arm trial of 199 patients. With a minimum of 6 months of treatment, 19% of patients experienced complete remission for a median of 8.2 months; 4% experienced complete remission with partial hematologic recovery for a median 9.6 months. Of the 157 patients who required blood or platelet transfusions due to AML at the start of the study, 34% no longer did after treatment with Idhifa.

Idhifa is approved for use with a companion diagnostic, the RealTime IDH2 Assay, which is used to detect mutations in the IDH2 gene in blood or bone marrow.

Source:

FDA approves new treatment for adults with relapsed or refractory acute lymphoblastic leukemia [news release]. Silver Spring, MD: U.S. Food & Drug Administration; August 17,2017. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm572131.htm. Accessed August 31, 2017.

FDA approves new targeted treatment for relapsed or refractory acute myeloid leukemia [news release]. Silver Spring, MD: U.S. Food & Drug Administration; August 1, 2017. https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm569421.htm. Accessed August 31, 2017.

FDA approves first treatment for certain types of poor-prognosis acute myeloid leukemia [news release]. Silver Spring, MD: U.S. Food & Drug Administration; August 3, 2017. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm569883.htm. Accessed August 31, 2017.

The U.S. Food and Drug Administration has approved tisagenlecleucel (Kymriah), a first-of-its-kind chimeric antigen receptor T-cell (CAR T) therapy, for the treatment of children and young adults up to age 25 years with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse.

Tisagenlecleucel will carry a boxed warning regarding the CRS risk. Additionally, due to the CRS risk and risk of neurological events, the approval requires a risk evaluation and mitigation strategy (REMS), which includes elements to assure safe use, according to an FDA press release.

Special certification will be required for hospitals and associated clinics that dispense tisagenlecleucel. As part of certification, staff will be trained in the prescribing, dispensing, or administering of the therapy, and to recognize and manage CRS and neurological events.

Novartis, the maker of tisagenlecleucel, will be required to conduct postmarketing observational study.

Courtesy Novartis

Indeed, FDA commissioner Scott Gottlieb, MD, said the approval marks the entry to a “new frontier in medical innovation.”

“New technologies such as gene and cell therapies hold out the potential to transform medicine and create an inflection point in our ability to treat and even cure many intractable illnesses,” he said in the press statement.

Tisagenlecleucel is a genetically modified autologous T-cell immunotherapy involving customized treatment created using a patient’s own T cells. The T cells are genetically modified to include a chimeric antigen receptor that directs the T cells to target and kill leukemia cells with CD19 surface antigen, and are then infused back into the patient. 

In a phase 2 clinical trial, the overall remission rate with tisagenlecleucel therapy was 83% in 63 children and young adults with relapsed/refractory B-cell precursor ALL for whom at least two prior lines of therapy had failed; the therapy was granted Fast Track, Priority Review, and Breakthrough Therapy designations.

“Kymriah is a first-of-its-kind treatment approach that fills an important unmet need for children and young adults with this serious disease,” Peter Marks, MD, director of the FDA’s Center for Biologics Evaluation and Research said in the press statement.

“Not only does Kymriah provide these patients with a new treatment option where very limited options existed, but a treatment option that shows promising remission and survival rates in clinical trials.”

At its meeting in July, the FDA ODAC agreed nearly unanimously that the risk mitigation plan put forward by Novartis, including planned 15-year follow-up and other mitigation measures, would be adequate for detecting serious consequences of CAR T-cell therapy.

sworcester@frontlinemedcom.com 

This article was updated August 30, 2017.

The U.S. Food and Drug Administration has approved tisagenlecleucel (Kymriah), a first-of-its-kind chimeric antigen receptor T-cell (CAR T) therapy, for the treatment of children and young adults up to age 25 years with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse.

Tisagenlecleucel will carry a boxed warning regarding the CRS risk. Additionally, due to the CRS risk and risk of neurological events, the approval requires a risk evaluation and mitigation strategy (REMS), which includes elements to assure safe use, according to an FDA press release.

Special certification will be required for hospitals and associated clinics that dispense tisagenlecleucel. As part of certification, staff will be trained in the prescribing, dispensing, or administering of the therapy, and to recognize and manage CRS and neurological events.

Novartis, the maker of tisagenlecleucel, will be required to conduct postmarketing observational study.

Courtesy Novartis

Indeed, FDA commissioner Scott Gottlieb, MD, said the approval marks the entry to a “new frontier in medical innovation.”

“New technologies such as gene and cell therapies hold out the potential to transform medicine and create an inflection point in our ability to treat and even cure many intractable illnesses,” he said in the press statement.

Tisagenlecleucel is a genetically modified autologous T-cell immunotherapy involving customized treatment created using a patient’s own T cells. The T cells are genetically modified to include a chimeric antigen receptor that directs the T cells to target and kill leukemia cells with CD19 surface antigen, and are then infused back into the patient. 

In a phase 2 clinical trial, the overall remission rate with tisagenlecleucel therapy was 83% in 63 children and young adults with relapsed/refractory B-cell precursor ALL for whom at least two prior lines of therapy had failed; the therapy was granted Fast Track, Priority Review, and Breakthrough Therapy designations.

“Kymriah is a first-of-its-kind treatment approach that fills an important unmet need for children and young adults with this serious disease,” Peter Marks, MD, director of the FDA’s Center for Biologics Evaluation and Research said in the press statement.

“Not only does Kymriah provide these patients with a new treatment option where very limited options existed, but a treatment option that shows promising remission and survival rates in clinical trials.”

At its meeting in July, the FDA ODAC agreed nearly unanimously that the risk mitigation plan put forward by Novartis, including planned 15-year follow-up and other mitigation measures, would be adequate for detecting serious consequences of CAR T-cell therapy.

sworcester@frontlinemedcom.com 

This article was updated August 30, 2017.

The U.S. Food and Drug Administration has approved tisagenlecleucel (Kymriah), a first-of-its-kind chimeric antigen receptor T-cell (CAR T) therapy, for the treatment of children and young adults up to age 25 years with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse.

Tisagenlecleucel will carry a boxed warning regarding the CRS risk. Additionally, due to the CRS risk and risk of neurological events, the approval requires a risk evaluation and mitigation strategy (REMS), which includes elements to assure safe use, according to an FDA press release.

Special certification will be required for hospitals and associated clinics that dispense tisagenlecleucel. As part of certification, staff will be trained in the prescribing, dispensing, or administering of the therapy, and to recognize and manage CRS and neurological events.

Novartis, the maker of tisagenlecleucel, will be required to conduct postmarketing observational study.

Courtesy Novartis

Indeed, FDA commissioner Scott Gottlieb, MD, said the approval marks the entry to a “new frontier in medical innovation.”

“New technologies such as gene and cell therapies hold out the potential to transform medicine and create an inflection point in our ability to treat and even cure many intractable illnesses,” he said in the press statement.

Tisagenlecleucel is a genetically modified autologous T-cell immunotherapy involving customized treatment created using a patient’s own T cells. The T cells are genetically modified to include a chimeric antigen receptor that directs the T cells to target and kill leukemia cells with CD19 surface antigen, and are then infused back into the patient. 

In a phase 2 clinical trial, the overall remission rate with tisagenlecleucel therapy was 83% in 63 children and young adults with relapsed/refractory B-cell precursor ALL for whom at least two prior lines of therapy had failed; the therapy was granted Fast Track, Priority Review, and Breakthrough Therapy designations.

“Kymriah is a first-of-its-kind treatment approach that fills an important unmet need for children and young adults with this serious disease,” Peter Marks, MD, director of the FDA’s Center for Biologics Evaluation and Research said in the press statement.

“Not only does Kymriah provide these patients with a new treatment option where very limited options existed, but a treatment option that shows promising remission and survival rates in clinical trials.”

At its meeting in July, the FDA ODAC agreed nearly unanimously that the risk mitigation plan put forward by Novartis, including planned 15-year follow-up and other mitigation measures, would be adequate for detecting serious consequences of CAR T-cell therapy.

sworcester@frontlinemedcom.com 

This article was updated August 30, 2017.