Hematology

Younger age of onset and the use of autologous hematopoietic stem cell transplant (ASCT) treatment were key factors improving the length of survival of newly diagnosed, active multiple myeloma (MM) patients, according to the results of a retrospective analysis.

In addition, multivariable analysis showed that a higher level of blood creatinine, the presence of extramedullary disease, a lower level of partial remission, and the use of nonautologous hematopoietic stem cell transplantation were independent risk factors for shorter survival, according to Virginia Bove, MD, of the Asociación Espanola Primera en Socorros Mutuos, Montevideo, Uruguay and colleagues.
 

Dr. Bove and colleagues retrospectively analyzed clinical characteristics, response to treatment, and survival of 282 patients from multiple institutions who had active newly-diagnosed multiple myeloma. They compared the results between patients age 65 years or younger (53.2%) with those older than 65 years and assessed clinical risk factors, as reported online in Hematology, Transfusion, and Cell Therapy.

The main cause of death in all patients was MM progression and the early mortality rate was not different between the younger and older patients. The main cause of early death in older patients was infection, according to the researchers.

Multiple risk factors

“Although MM patients younger than 66 years of age have an aggressive presentation with an advanced stage, high rate of renal failure and extramedullary disease, this did not translate into an inferior [overall survival] and [progression-free survival],” the researchers reported.

The overall response rate was similar between groups (80.6% vs. 81.4%; P = .866), and the overall survival was significantly longer in young patients (median, 65 months vs. 41 months; P = .001) and higher in those who received autologous hematopoietic stem cell transplantation.

Multivariate analysis was performed on data from the younger patients. The results showed that a creatinine level of less than or equal to 2 mg/dL (P = .048), extramedullary disease (P = .001), a lower VGPR (P = .003) and the use of nonautologous hematopoietic stem cell transplantation (P = .048) were all independent risk factors for shorter survival.

“Older age is an independent adverse prognostic factor. Adequate risk identification, frontline treatment based on novel drugs and ASCT are the best strategies to improve outcomes, both in young and old patients,” the researchers concluded.

The authors reported that they had no conflicts of interest.

mlesney@mdedge.com

SOURCE: Bove V et al. Hematol Transfus Cell Ther. 2020 Aug 20. doi: 10.1016/j.htct.2020.06.014.

Younger age of onset and the use of autologous hematopoietic stem cell transplant (ASCT) treatment were key factors improving the length of survival of newly diagnosed, active multiple myeloma (MM) patients, according to the results of a retrospective analysis.

In addition, multivariable analysis showed that a higher level of blood creatinine, the presence of extramedullary disease, a lower level of partial remission, and the use of nonautologous hematopoietic stem cell transplantation were independent risk factors for shorter survival, according to Virginia Bove, MD, of the Asociación Espanola Primera en Socorros Mutuos, Montevideo, Uruguay and colleagues.
 

Dr. Bove and colleagues retrospectively analyzed clinical characteristics, response to treatment, and survival of 282 patients from multiple institutions who had active newly-diagnosed multiple myeloma. They compared the results between patients age 65 years or younger (53.2%) with those older than 65 years and assessed clinical risk factors, as reported online in Hematology, Transfusion, and Cell Therapy.

The main cause of death in all patients was MM progression and the early mortality rate was not different between the younger and older patients. The main cause of early death in older patients was infection, according to the researchers.

Multiple risk factors

“Although MM patients younger than 66 years of age have an aggressive presentation with an advanced stage, high rate of renal failure and extramedullary disease, this did not translate into an inferior [overall survival] and [progression-free survival],” the researchers reported.

The overall response rate was similar between groups (80.6% vs. 81.4%; P = .866), and the overall survival was significantly longer in young patients (median, 65 months vs. 41 months; P = .001) and higher in those who received autologous hematopoietic stem cell transplantation.

Multivariate analysis was performed on data from the younger patients. The results showed that a creatinine level of less than or equal to 2 mg/dL (P = .048), extramedullary disease (P = .001), a lower VGPR (P = .003) and the use of nonautologous hematopoietic stem cell transplantation (P = .048) were all independent risk factors for shorter survival.

“Older age is an independent adverse prognostic factor. Adequate risk identification, frontline treatment based on novel drugs and ASCT are the best strategies to improve outcomes, both in young and old patients,” the researchers concluded.

The authors reported that they had no conflicts of interest.

mlesney@mdedge.com

SOURCE: Bove V et al. Hematol Transfus Cell Ther. 2020 Aug 20. doi: 10.1016/j.htct.2020.06.014.

Younger age of onset and the use of autologous hematopoietic stem cell transplant (ASCT) treatment were key factors improving the length of survival of newly diagnosed, active multiple myeloma (MM) patients, according to the results of a retrospective analysis.

In addition, multivariable analysis showed that a higher level of blood creatinine, the presence of extramedullary disease, a lower level of partial remission, and the use of nonautologous hematopoietic stem cell transplantation were independent risk factors for shorter survival, according to Virginia Bove, MD, of the Asociación Espanola Primera en Socorros Mutuos, Montevideo, Uruguay and colleagues.
 

Dr. Bove and colleagues retrospectively analyzed clinical characteristics, response to treatment, and survival of 282 patients from multiple institutions who had active newly-diagnosed multiple myeloma. They compared the results between patients age 65 years or younger (53.2%) with those older than 65 years and assessed clinical risk factors, as reported online in Hematology, Transfusion, and Cell Therapy.

The main cause of death in all patients was MM progression and the early mortality rate was not different between the younger and older patients. The main cause of early death in older patients was infection, according to the researchers.

Multiple risk factors

“Although MM patients younger than 66 years of age have an aggressive presentation with an advanced stage, high rate of renal failure and extramedullary disease, this did not translate into an inferior [overall survival] and [progression-free survival],” the researchers reported.

The overall response rate was similar between groups (80.6% vs. 81.4%; P = .866), and the overall survival was significantly longer in young patients (median, 65 months vs. 41 months; P = .001) and higher in those who received autologous hematopoietic stem cell transplantation.

Multivariate analysis was performed on data from the younger patients. The results showed that a creatinine level of less than or equal to 2 mg/dL (P = .048), extramedullary disease (P = .001), a lower VGPR (P = .003) and the use of nonautologous hematopoietic stem cell transplantation (P = .048) were all independent risk factors for shorter survival.

“Older age is an independent adverse prognostic factor. Adequate risk identification, frontline treatment based on novel drugs and ASCT are the best strategies to improve outcomes, both in young and old patients,” the researchers concluded.

The authors reported that they had no conflicts of interest.

mlesney@mdedge.com

SOURCE: Bove V et al. Hematol Transfus Cell Ther. 2020 Aug 20. doi: 10.1016/j.htct.2020.06.014.

A new study has quantified cancer risk factors in patients with systemic lupus erythematosus, including smoking and the use of certain medications.

“As expected, older age was associated with cancer overall, as well as with the most common cancer subtypes,” wrote Sasha Bernatsky, MD, PhD, of McGill University, Montreal, and coauthors. The study was published in Arthritis Care & Research.

To determine the risk of cancer in people with clinically confirmed incident systemic lupus erythematosus (SLE), the researchers analyzed data from 1,668 newly diagnosed lupus patients with at least one follow-up visit. All patients were enrolled in the Systemic Lupus International Collaborating Clinics inception cohort from across 33 different centers in North America, Europe, and Asia. A total of 89% (n = 1,480) were women, and 49% (n = 824) were white. The average follow-up period was 9 years.

Of the 1,668 SLE patients, 65 developed some type of cancer. The cancers included 15 breast;, 10 nonmelanoma skin; 7 lung; 6 hematologic, 6 prostate; 5 melanoma; 3 cervical; 3 renal; 2 gastric; 2 head and neck; 2 thyroid; and 1 rectal, sarcoma, thymoma, or uterine. No patient had more than one type, and the mean age of the cancer patients at time of SLE diagnosis was 45.6 (standard deviation, 14.5).

Almost half of the 65 cancers occurred in past or current smokers, including all of the lung cancers, while only 33% of patients without cancers smoked prior to baseline. After univariate analysis, characteristics associated with a higher risk of all cancers included older age at SLE diagnosis (adjusted hazard ratio, 1.05; 95% confidence interval, 1.03-1.06), White race/ethnicity (aHR 1.34; 95% CI, 0.76-2.37), and smoking (aHR 1.21; 95% CI, 0.73-2.01).

After multivariate analysis, the two characteristics most associated with increased cancer risk were older age at SLE diagnosis and being male. The analyses also confirmed that older age was a risk factor for breast cancer (aHR 1.06; 95% CI, 1.02-1.10) and nonmelanoma skin cancer (aHR, 1.06; 95% CI, 1.02-1.11), while use of antimalarial drugs was associated with a lower risk of both breast (aHR, 0.28; 95% CI, 0.09-0.90) and nonmelanoma skin (aHR, 0.23; 95% CI, 0.05-0.95) cancers. For lung cancer, the highest risk factor was smoking 15 or more cigarettes a day (aHR, 6.64; 95% CI, 1.43-30.9); for hematologic cancers, it was being in the top quartile of SLE disease activity (aHR, 7.14; 95% CI, 1.13-45.3).

The authors acknowledged their study’s limitations, including the small number of cancers overall and purposefully not comparing cancer risk in SLE patients with risk in the general population. Although their methods – “physicians recording events at annual visits, confirmed by review of charts” – were recognized as very suitable for the current analysis, they noted that a broader comparison would “potentially be problematic due to differential misclassification error” in cancer registry data.

Two of the study’s authors reported potential conflicts of interest, including receiving grants and consulting and personal fees from various pharmaceutical companies. No other potential conflicts were reported.

SOURCE: Bernatsky S et al. Arthritis Care Res. 2020 Aug 19. doi: 10.1002/acr.24425.

A new study has quantified cancer risk factors in patients with systemic lupus erythematosus, including smoking and the use of certain medications.

“As expected, older age was associated with cancer overall, as well as with the most common cancer subtypes,” wrote Sasha Bernatsky, MD, PhD, of McGill University, Montreal, and coauthors. The study was published in Arthritis Care & Research.

To determine the risk of cancer in people with clinically confirmed incident systemic lupus erythematosus (SLE), the researchers analyzed data from 1,668 newly diagnosed lupus patients with at least one follow-up visit. All patients were enrolled in the Systemic Lupus International Collaborating Clinics inception cohort from across 33 different centers in North America, Europe, and Asia. A total of 89% (n = 1,480) were women, and 49% (n = 824) were white. The average follow-up period was 9 years.

Of the 1,668 SLE patients, 65 developed some type of cancer. The cancers included 15 breast;, 10 nonmelanoma skin; 7 lung; 6 hematologic, 6 prostate; 5 melanoma; 3 cervical; 3 renal; 2 gastric; 2 head and neck; 2 thyroid; and 1 rectal, sarcoma, thymoma, or uterine. No patient had more than one type, and the mean age of the cancer patients at time of SLE diagnosis was 45.6 (standard deviation, 14.5).

Almost half of the 65 cancers occurred in past or current smokers, including all of the lung cancers, while only 33% of patients without cancers smoked prior to baseline. After univariate analysis, characteristics associated with a higher risk of all cancers included older age at SLE diagnosis (adjusted hazard ratio, 1.05; 95% confidence interval, 1.03-1.06), White race/ethnicity (aHR 1.34; 95% CI, 0.76-2.37), and smoking (aHR 1.21; 95% CI, 0.73-2.01).

After multivariate analysis, the two characteristics most associated with increased cancer risk were older age at SLE diagnosis and being male. The analyses also confirmed that older age was a risk factor for breast cancer (aHR 1.06; 95% CI, 1.02-1.10) and nonmelanoma skin cancer (aHR, 1.06; 95% CI, 1.02-1.11), while use of antimalarial drugs was associated with a lower risk of both breast (aHR, 0.28; 95% CI, 0.09-0.90) and nonmelanoma skin (aHR, 0.23; 95% CI, 0.05-0.95) cancers. For lung cancer, the highest risk factor was smoking 15 or more cigarettes a day (aHR, 6.64; 95% CI, 1.43-30.9); for hematologic cancers, it was being in the top quartile of SLE disease activity (aHR, 7.14; 95% CI, 1.13-45.3).

The authors acknowledged their study’s limitations, including the small number of cancers overall and purposefully not comparing cancer risk in SLE patients with risk in the general population. Although their methods – “physicians recording events at annual visits, confirmed by review of charts” – were recognized as very suitable for the current analysis, they noted that a broader comparison would “potentially be problematic due to differential misclassification error” in cancer registry data.

Two of the study’s authors reported potential conflicts of interest, including receiving grants and consulting and personal fees from various pharmaceutical companies. No other potential conflicts were reported.

SOURCE: Bernatsky S et al. Arthritis Care Res. 2020 Aug 19. doi: 10.1002/acr.24425.

A new study has quantified cancer risk factors in patients with systemic lupus erythematosus, including smoking and the use of certain medications.

“As expected, older age was associated with cancer overall, as well as with the most common cancer subtypes,” wrote Sasha Bernatsky, MD, PhD, of McGill University, Montreal, and coauthors. The study was published in Arthritis Care & Research.

To determine the risk of cancer in people with clinically confirmed incident systemic lupus erythematosus (SLE), the researchers analyzed data from 1,668 newly diagnosed lupus patients with at least one follow-up visit. All patients were enrolled in the Systemic Lupus International Collaborating Clinics inception cohort from across 33 different centers in North America, Europe, and Asia. A total of 89% (n = 1,480) were women, and 49% (n = 824) were white. The average follow-up period was 9 years.

Of the 1,668 SLE patients, 65 developed some type of cancer. The cancers included 15 breast;, 10 nonmelanoma skin; 7 lung; 6 hematologic, 6 prostate; 5 melanoma; 3 cervical; 3 renal; 2 gastric; 2 head and neck; 2 thyroid; and 1 rectal, sarcoma, thymoma, or uterine. No patient had more than one type, and the mean age of the cancer patients at time of SLE diagnosis was 45.6 (standard deviation, 14.5).

Almost half of the 65 cancers occurred in past or current smokers, including all of the lung cancers, while only 33% of patients without cancers smoked prior to baseline. After univariate analysis, characteristics associated with a higher risk of all cancers included older age at SLE diagnosis (adjusted hazard ratio, 1.05; 95% confidence interval, 1.03-1.06), White race/ethnicity (aHR 1.34; 95% CI, 0.76-2.37), and smoking (aHR 1.21; 95% CI, 0.73-2.01).

After multivariate analysis, the two characteristics most associated with increased cancer risk were older age at SLE diagnosis and being male. The analyses also confirmed that older age was a risk factor for breast cancer (aHR 1.06; 95% CI, 1.02-1.10) and nonmelanoma skin cancer (aHR, 1.06; 95% CI, 1.02-1.11), while use of antimalarial drugs was associated with a lower risk of both breast (aHR, 0.28; 95% CI, 0.09-0.90) and nonmelanoma skin (aHR, 0.23; 95% CI, 0.05-0.95) cancers. For lung cancer, the highest risk factor was smoking 15 or more cigarettes a day (aHR, 6.64; 95% CI, 1.43-30.9); for hematologic cancers, it was being in the top quartile of SLE disease activity (aHR, 7.14; 95% CI, 1.13-45.3).

The authors acknowledged their study’s limitations, including the small number of cancers overall and purposefully not comparing cancer risk in SLE patients with risk in the general population. Although their methods – “physicians recording events at annual visits, confirmed by review of charts” – were recognized as very suitable for the current analysis, they noted that a broader comparison would “potentially be problematic due to differential misclassification error” in cancer registry data.

Two of the study’s authors reported potential conflicts of interest, including receiving grants and consulting and personal fees from various pharmaceutical companies. No other potential conflicts were reported.

SOURCE: Bernatsky S et al. Arthritis Care Res. 2020 Aug 19. doi: 10.1002/acr.24425.

Although patients with acute lymphoblastic leukemia (ALL) are at known risk of venous thromboembolism (VTE), there was no overall genetic correlation found to be associated with that susceptibility in the overall population. However, a significant genetic predisposition to VTE was found in adolescent ALL patients, according to a report published in Thrombosis Research.

The researchers assessed the prospectively registered VTE events and collected germline DNA in patients aged 1-45.9 years in the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 study, which took place from 2008 to 2016. The researchers performed polygenic risk score (PRS) analysis on VTE development in the NOPHO cohort, according to Kirsten Brunsvig Jarvis, MD, of Oslo University Hospital, and colleagues.

The researchers used summary statistics from two large genomewide association studies on VTE in adults (the International Network of Venous Thromboembolism Clinical Research Networks [INVENT] consortium and the UK Biobank).

Of 1,252 patients with ALL in the genetic cohort, 89 developed VTE (2.5-year cumulative incidence, 7.2%; 95% confidence interval,5.7-8.6) at a median 12.7 weeks from diagnosis.

Overall, an analysis of single-nucleotide polymorphisms (SNPs) from INVENT and UK Biobank studies did not reveal evidence of polygenic correlation with VTE in patients with ALL, the researchers reported. However, when separating adolescents aged 10.0-17.9 years (n = 231) from adults aged 18 years or older (n = 127), they saw polygenic overlap between the INVENT study and thromboembolism development in the adolescent population.

The best-fit polygenic risk score, including 16,144 SNPs, was associated with VTE in adolescents with ALL at a hazard ratio of 1.76 (95% CI, 1.23-2.52; P = .02).
 

Adolescent vs. adult risk

The researchers expressed surprise that they did not find evidence of genetic overlap in adults. But they stated that, in general, VTE occurs more frequently in adults as part of natural aging, while children and adolescents are physiologically protected. This might explain why genetics might play a stronger role in the high-risk situation of cancer and chemotherapy in adolescents who do not have as many additional exogenic risk factors as adults.

“The usefulness of genetic studies on [V]TE in the general adult population is limited when it comes to understanding the etiology of [V]TE in patients with ALL. However, we found evidence of polygenic overlap in subgroup analysis of adolescents aged 10.0-17.9 years with ALL, and we believe the genetics of [V]TE in this group should be further explored in future risk prediction models for identification of those who might benefit from thromboprophylaxis,” the researchers concluded.

The study was supported by research grant from the South-Eastern Norway Regional Health Authority. The authors reported that they had no conflicts of interest.

mlesney@mdedge.com

SOURCE: Jarvis KB et al. Thromb Res. 2020 Aug 11.doi: 10.1016/j.thromres.2020.08.015.

Although patients with acute lymphoblastic leukemia (ALL) are at known risk of venous thromboembolism (VTE), there was no overall genetic correlation found to be associated with that susceptibility in the overall population. However, a significant genetic predisposition to VTE was found in adolescent ALL patients, according to a report published in Thrombosis Research.

The researchers assessed the prospectively registered VTE events and collected germline DNA in patients aged 1-45.9 years in the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 study, which took place from 2008 to 2016. The researchers performed polygenic risk score (PRS) analysis on VTE development in the NOPHO cohort, according to Kirsten Brunsvig Jarvis, MD, of Oslo University Hospital, and colleagues.

The researchers used summary statistics from two large genomewide association studies on VTE in adults (the International Network of Venous Thromboembolism Clinical Research Networks [INVENT] consortium and the UK Biobank).

Of 1,252 patients with ALL in the genetic cohort, 89 developed VTE (2.5-year cumulative incidence, 7.2%; 95% confidence interval,5.7-8.6) at a median 12.7 weeks from diagnosis.

Overall, an analysis of single-nucleotide polymorphisms (SNPs) from INVENT and UK Biobank studies did not reveal evidence of polygenic correlation with VTE in patients with ALL, the researchers reported. However, when separating adolescents aged 10.0-17.9 years (n = 231) from adults aged 18 years or older (n = 127), they saw polygenic overlap between the INVENT study and thromboembolism development in the adolescent population.

The best-fit polygenic risk score, including 16,144 SNPs, was associated with VTE in adolescents with ALL at a hazard ratio of 1.76 (95% CI, 1.23-2.52; P = .02).
 

Adolescent vs. adult risk

The researchers expressed surprise that they did not find evidence of genetic overlap in adults. But they stated that, in general, VTE occurs more frequently in adults as part of natural aging, while children and adolescents are physiologically protected. This might explain why genetics might play a stronger role in the high-risk situation of cancer and chemotherapy in adolescents who do not have as many additional exogenic risk factors as adults.

“The usefulness of genetic studies on [V]TE in the general adult population is limited when it comes to understanding the etiology of [V]TE in patients with ALL. However, we found evidence of polygenic overlap in subgroup analysis of adolescents aged 10.0-17.9 years with ALL, and we believe the genetics of [V]TE in this group should be further explored in future risk prediction models for identification of those who might benefit from thromboprophylaxis,” the researchers concluded.

The study was supported by research grant from the South-Eastern Norway Regional Health Authority. The authors reported that they had no conflicts of interest.

mlesney@mdedge.com

SOURCE: Jarvis KB et al. Thromb Res. 2020 Aug 11.doi: 10.1016/j.thromres.2020.08.015.

Although patients with acute lymphoblastic leukemia (ALL) are at known risk of venous thromboembolism (VTE), there was no overall genetic correlation found to be associated with that susceptibility in the overall population. However, a significant genetic predisposition to VTE was found in adolescent ALL patients, according to a report published in Thrombosis Research.

The researchers assessed the prospectively registered VTE events and collected germline DNA in patients aged 1-45.9 years in the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 study, which took place from 2008 to 2016. The researchers performed polygenic risk score (PRS) analysis on VTE development in the NOPHO cohort, according to Kirsten Brunsvig Jarvis, MD, of Oslo University Hospital, and colleagues.

The researchers used summary statistics from two large genomewide association studies on VTE in adults (the International Network of Venous Thromboembolism Clinical Research Networks [INVENT] consortium and the UK Biobank).

Of 1,252 patients with ALL in the genetic cohort, 89 developed VTE (2.5-year cumulative incidence, 7.2%; 95% confidence interval,5.7-8.6) at a median 12.7 weeks from diagnosis.

Overall, an analysis of single-nucleotide polymorphisms (SNPs) from INVENT and UK Biobank studies did not reveal evidence of polygenic correlation with VTE in patients with ALL, the researchers reported. However, when separating adolescents aged 10.0-17.9 years (n = 231) from adults aged 18 years or older (n = 127), they saw polygenic overlap between the INVENT study and thromboembolism development in the adolescent population.

The best-fit polygenic risk score, including 16,144 SNPs, was associated with VTE in adolescents with ALL at a hazard ratio of 1.76 (95% CI, 1.23-2.52; P = .02).
 

Adolescent vs. adult risk

The researchers expressed surprise that they did not find evidence of genetic overlap in adults. But they stated that, in general, VTE occurs more frequently in adults as part of natural aging, while children and adolescents are physiologically protected. This might explain why genetics might play a stronger role in the high-risk situation of cancer and chemotherapy in adolescents who do not have as many additional exogenic risk factors as adults.

“The usefulness of genetic studies on [V]TE in the general adult population is limited when it comes to understanding the etiology of [V]TE in patients with ALL. However, we found evidence of polygenic overlap in subgroup analysis of adolescents aged 10.0-17.9 years with ALL, and we believe the genetics of [V]TE in this group should be further explored in future risk prediction models for identification of those who might benefit from thromboprophylaxis,” the researchers concluded.

The study was supported by research grant from the South-Eastern Norway Regional Health Authority. The authors reported that they had no conflicts of interest.

mlesney@mdedge.com

SOURCE: Jarvis KB et al. Thromb Res. 2020 Aug 11.doi: 10.1016/j.thromres.2020.08.015.

The BALL score was able to identify a subset of patients with chronic lymphocytic leukemia (CLL) who particularly benefit from single-agent ibrutinib therapy, according to the results of a study of 111 patients followed from two different institutions.

The BALL model consists of four factors: serum beta₂-microglobulin at 5 mg/dL or greater, hemoglobin < 110 g/L for women or < 120 g/L for men, lactate dehydrogenase [LDH] > upper limit of normal [UNL], and time elapsed from last therapy less than 24 months. Each parameter was alloted 1 point, leading to a stratification of patients into three different prognostic groups: low risk (score 0-1), intermediate risk (2-3), and high risk (score 4), according to a report published online in Leukemia Research.

According to Stefano Molica, MD, of the Azienda Ospedaliera Pugliese-Ciaccio, Catanzaro, Italy, and his colleagues, the majority of patients (82%) were clinical Rai stage II-IV. The median patient age was 63 years and nearly 68% were men.

The researchers assessed four models for predicting overall survival. The modified version of CLL-International Prognostic Index (CLL-IPI) failed to provide prognostic information in relapsed/refractory (R/R) CLL (P = .77) as did the Ahn et al. model (P = .95) and a simplified BALL model (P = .09). In contrast, the full BALL score captured two groups of patients with significant differences in survival (hazard ratio, 0.240; 95 % confidence interval, 0.10-0.54; P = .0005); however, because of the low number of patients in the high-risk category, these cases were combined with the intermediate-risk group.

The BALL score identified a subset of patients, accounting for about 50% of the whole population, who particularly benefit from single-agent ibrutinib, according to Dr. Molica and his colleagues. These patients had a survival rate of 85% at 3 years.

“In contrast, the outcome of subjects with intermediate-high risk is disappointing. These patients should be considered for a combination of targeted drugs or cellular-based therapies,” the researchers concluded.

The authors reported that they had no conflicts.

mlesney@mdedge.com

SOURCE: Molica S et al. Leuk Res. 2020 Jun 10. https://doi.org/10.1016/j.leukres.2020.

The BALL score was able to identify a subset of patients with chronic lymphocytic leukemia (CLL) who particularly benefit from single-agent ibrutinib therapy, according to the results of a study of 111 patients followed from two different institutions.

The BALL model consists of four factors: serum beta₂-microglobulin at 5 mg/dL or greater, hemoglobin < 110 g/L for women or < 120 g/L for men, lactate dehydrogenase [LDH] > upper limit of normal [UNL], and time elapsed from last therapy less than 24 months. Each parameter was alloted 1 point, leading to a stratification of patients into three different prognostic groups: low risk (score 0-1), intermediate risk (2-3), and high risk (score 4), according to a report published online in Leukemia Research.

According to Stefano Molica, MD, of the Azienda Ospedaliera Pugliese-Ciaccio, Catanzaro, Italy, and his colleagues, the majority of patients (82%) were clinical Rai stage II-IV. The median patient age was 63 years and nearly 68% were men.

The researchers assessed four models for predicting overall survival. The modified version of CLL-International Prognostic Index (CLL-IPI) failed to provide prognostic information in relapsed/refractory (R/R) CLL (P = .77) as did the Ahn et al. model (P = .95) and a simplified BALL model (P = .09). In contrast, the full BALL score captured two groups of patients with significant differences in survival (hazard ratio, 0.240; 95 % confidence interval, 0.10-0.54; P = .0005); however, because of the low number of patients in the high-risk category, these cases were combined with the intermediate-risk group.

The BALL score identified a subset of patients, accounting for about 50% of the whole population, who particularly benefit from single-agent ibrutinib, according to Dr. Molica and his colleagues. These patients had a survival rate of 85% at 3 years.

“In contrast, the outcome of subjects with intermediate-high risk is disappointing. These patients should be considered for a combination of targeted drugs or cellular-based therapies,” the researchers concluded.

The authors reported that they had no conflicts.

mlesney@mdedge.com

SOURCE: Molica S et al. Leuk Res. 2020 Jun 10. https://doi.org/10.1016/j.leukres.2020.

The BALL score was able to identify a subset of patients with chronic lymphocytic leukemia (CLL) who particularly benefit from single-agent ibrutinib therapy, according to the results of a study of 111 patients followed from two different institutions.

The BALL model consists of four factors: serum beta₂-microglobulin at 5 mg/dL or greater, hemoglobin < 110 g/L for women or < 120 g/L for men, lactate dehydrogenase [LDH] > upper limit of normal [UNL], and time elapsed from last therapy less than 24 months. Each parameter was alloted 1 point, leading to a stratification of patients into three different prognostic groups: low risk (score 0-1), intermediate risk (2-3), and high risk (score 4), according to a report published online in Leukemia Research.

According to Stefano Molica, MD, of the Azienda Ospedaliera Pugliese-Ciaccio, Catanzaro, Italy, and his colleagues, the majority of patients (82%) were clinical Rai stage II-IV. The median patient age was 63 years and nearly 68% were men.

The researchers assessed four models for predicting overall survival. The modified version of CLL-International Prognostic Index (CLL-IPI) failed to provide prognostic information in relapsed/refractory (R/R) CLL (P = .77) as did the Ahn et al. model (P = .95) and a simplified BALL model (P = .09). In contrast, the full BALL score captured two groups of patients with significant differences in survival (hazard ratio, 0.240; 95 % confidence interval, 0.10-0.54; P = .0005); however, because of the low number of patients in the high-risk category, these cases were combined with the intermediate-risk group.

The BALL score identified a subset of patients, accounting for about 50% of the whole population, who particularly benefit from single-agent ibrutinib, according to Dr. Molica and his colleagues. These patients had a survival rate of 85% at 3 years.

“In contrast, the outcome of subjects with intermediate-high risk is disappointing. These patients should be considered for a combination of targeted drugs or cellular-based therapies,” the researchers concluded.

The authors reported that they had no conflicts.

mlesney@mdedge.com

SOURCE: Molica S et al. Leuk Res. 2020 Jun 10. https://doi.org/10.1016/j.leukres.2020.

A novel drug, tafasitamab-cxix (Monjuvi, MorphoSys US), has been approved by the Food and Drug Administration for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

The product is a humanized Fc-modified cytolytic CD19 targeting monoclonal antibody. It mediates B-cell lysis through apoptosis and immune effector mechanism, including antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).

It is indicated for use in combination with lenalidomide for adult patients with relapsed/refractory DLBCL that is not otherwise specified, including DLBCL arising from low-grade lymphoma, and in patients who are not eligible for autologous stem cell transplant (ASCT).

Tafasitamab-cxix in combination with lenalidomide is the first treatment that approved by the FDA for second-line use for patients with relapsed or refractory DLBCL, notes the manufacturer.

The approval “brings a new treatment option to patients in dire need across the United States,” said Gilles Salles, MD, chair of the clinical hematology department at the University of Lyon (France), and lead investigator of the L-MIND study.

The FDA granted an accelerated approval on the basis of overall response rate from an open-label, single-arm, phase 2 trial in 81 patients (known as L-MIND). Further trials are underway to confirm clinical benefit.

The L-MIND trial was conducted in patients with relapsed or refractory DLBCL who had received at least one, but no more than three, prior lines of therapy, including an anti-CD20 targeting therapy (e.g., rituximab), who were not eligible for high-dose chemotherapy or who refused subsequent ASCT.

All patients received tafasitamab-cxix 12 mg/kg intravenously with lenalidomide (25 mg orally on days 1-21 of each 28-day cycle) for a maximum of 12 cycles, followed by tafasitamab-cxix as monotherapy.

The best ORR (defined as complete and partial responders) in 71 patients with a diagnosis of DLBCL confirmed by central pathology was 55%, with complete responses in 37% and partial responses in 18% of patients. The median response duration was 21.7 months (range, 0-24).

The most common adverse reactions (≥20%) were neutropenia, fatigue, anemia, diarrhea, thrombocytopenia, cough, fever, peripheral edema, respiratory tract infection, and decreased appetite.

Precautions and warnings include infusion-related reactions (6%), serious or severe myelosuppression (including neutropenia [50%], thrombocytopenia [18%], and anemia [7%]), infections (73%), and embryo-fetal toxicity.

DLBCL is the most common type of non-Hodgkin lymphoma in adults worldwide, characterized by rapidly growing masses of malignant B-cells in the lymph nodes, spleen, liver, bone marrow or other organs. It is an aggressive disease with about one in three patients not responding to initial therapy or relapsing thereafter, notes the manufacturer. In the United States each year approximately 10,000 patients who are not eligible for ASCT are diagnosed with relapsed or refractory DLBCL.

This article first appeared on Medscape.com.

A novel drug, tafasitamab-cxix (Monjuvi, MorphoSys US), has been approved by the Food and Drug Administration for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

The product is a humanized Fc-modified cytolytic CD19 targeting monoclonal antibody. It mediates B-cell lysis through apoptosis and immune effector mechanism, including antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).

It is indicated for use in combination with lenalidomide for adult patients with relapsed/refractory DLBCL that is not otherwise specified, including DLBCL arising from low-grade lymphoma, and in patients who are not eligible for autologous stem cell transplant (ASCT).

Tafasitamab-cxix in combination with lenalidomide is the first treatment that approved by the FDA for second-line use for patients with relapsed or refractory DLBCL, notes the manufacturer.

The approval “brings a new treatment option to patients in dire need across the United States,” said Gilles Salles, MD, chair of the clinical hematology department at the University of Lyon (France), and lead investigator of the L-MIND study.

The FDA granted an accelerated approval on the basis of overall response rate from an open-label, single-arm, phase 2 trial in 81 patients (known as L-MIND). Further trials are underway to confirm clinical benefit.

The L-MIND trial was conducted in patients with relapsed or refractory DLBCL who had received at least one, but no more than three, prior lines of therapy, including an anti-CD20 targeting therapy (e.g., rituximab), who were not eligible for high-dose chemotherapy or who refused subsequent ASCT.

All patients received tafasitamab-cxix 12 mg/kg intravenously with lenalidomide (25 mg orally on days 1-21 of each 28-day cycle) for a maximum of 12 cycles, followed by tafasitamab-cxix as monotherapy.

The best ORR (defined as complete and partial responders) in 71 patients with a diagnosis of DLBCL confirmed by central pathology was 55%, with complete responses in 37% and partial responses in 18% of patients. The median response duration was 21.7 months (range, 0-24).

The most common adverse reactions (≥20%) were neutropenia, fatigue, anemia, diarrhea, thrombocytopenia, cough, fever, peripheral edema, respiratory tract infection, and decreased appetite.

Precautions and warnings include infusion-related reactions (6%), serious or severe myelosuppression (including neutropenia [50%], thrombocytopenia [18%], and anemia [7%]), infections (73%), and embryo-fetal toxicity.

DLBCL is the most common type of non-Hodgkin lymphoma in adults worldwide, characterized by rapidly growing masses of malignant B-cells in the lymph nodes, spleen, liver, bone marrow or other organs. It is an aggressive disease with about one in three patients not responding to initial therapy or relapsing thereafter, notes the manufacturer. In the United States each year approximately 10,000 patients who are not eligible for ASCT are diagnosed with relapsed or refractory DLBCL.

This article first appeared on Medscape.com.

A novel drug, tafasitamab-cxix (Monjuvi, MorphoSys US), has been approved by the Food and Drug Administration for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

The product is a humanized Fc-modified cytolytic CD19 targeting monoclonal antibody. It mediates B-cell lysis through apoptosis and immune effector mechanism, including antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).

It is indicated for use in combination with lenalidomide for adult patients with relapsed/refractory DLBCL that is not otherwise specified, including DLBCL arising from low-grade lymphoma, and in patients who are not eligible for autologous stem cell transplant (ASCT).

Tafasitamab-cxix in combination with lenalidomide is the first treatment that approved by the FDA for second-line use for patients with relapsed or refractory DLBCL, notes the manufacturer.

The approval “brings a new treatment option to patients in dire need across the United States,” said Gilles Salles, MD, chair of the clinical hematology department at the University of Lyon (France), and lead investigator of the L-MIND study.

The FDA granted an accelerated approval on the basis of overall response rate from an open-label, single-arm, phase 2 trial in 81 patients (known as L-MIND). Further trials are underway to confirm clinical benefit.

The L-MIND trial was conducted in patients with relapsed or refractory DLBCL who had received at least one, but no more than three, prior lines of therapy, including an anti-CD20 targeting therapy (e.g., rituximab), who were not eligible for high-dose chemotherapy or who refused subsequent ASCT.

All patients received tafasitamab-cxix 12 mg/kg intravenously with lenalidomide (25 mg orally on days 1-21 of each 28-day cycle) for a maximum of 12 cycles, followed by tafasitamab-cxix as monotherapy.

The best ORR (defined as complete and partial responders) in 71 patients with a diagnosis of DLBCL confirmed by central pathology was 55%, with complete responses in 37% and partial responses in 18% of patients. The median response duration was 21.7 months (range, 0-24).

The most common adverse reactions (≥20%) were neutropenia, fatigue, anemia, diarrhea, thrombocytopenia, cough, fever, peripheral edema, respiratory tract infection, and decreased appetite.

Precautions and warnings include infusion-related reactions (6%), serious or severe myelosuppression (including neutropenia [50%], thrombocytopenia [18%], and anemia [7%]), infections (73%), and embryo-fetal toxicity.

DLBCL is the most common type of non-Hodgkin lymphoma in adults worldwide, characterized by rapidly growing masses of malignant B-cells in the lymph nodes, spleen, liver, bone marrow or other organs. It is an aggressive disease with about one in three patients not responding to initial therapy or relapsing thereafter, notes the manufacturer. In the United States each year approximately 10,000 patients who are not eligible for ASCT are diagnosed with relapsed or refractory DLBCL.

This article first appeared on Medscape.com.

Background: Antiplatelet agents reduce the risk of major vascular events in patient with established vaso-occlusive disease, but they may increase the risk of ICH. Patients with prior ICH are at risk for both vaso-occlusive and hemorrhagic events. Clarification of the relative risk and benefit of antiplatelet agent use in this clinical scenario would serve to guide therapy.

Hospitalists should be aware that these data suggest that the risk assessment for resumption of antiplatelet agents should not be affected by a history of nontraumatic intracerebral hemorrhage when weighed against the benefit of these medications in patients with occlusive vascular disease.

Bottom line: Resumption of antiplatelet agents following intracerebral hemorrhage showed no evidence of increased risk of recurrent intracerebral hemorrhage or major hemorrhagic events.

Citation: RESTART Collaboration. Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): A randomized, open-label trial. Lancet. 2019. doi: 10.1016/S0140-6736(19)30840-2.

Dr. Deitelzweig is system department chair of hospital medicine at Ochsner Health System, New Orleans.

Background: Antiplatelet agents reduce the risk of major vascular events in patient with established vaso-occlusive disease, but they may increase the risk of ICH. Patients with prior ICH are at risk for both vaso-occlusive and hemorrhagic events. Clarification of the relative risk and benefit of antiplatelet agent use in this clinical scenario would serve to guide therapy.

Hospitalists should be aware that these data suggest that the risk assessment for resumption of antiplatelet agents should not be affected by a history of nontraumatic intracerebral hemorrhage when weighed against the benefit of these medications in patients with occlusive vascular disease.

Bottom line: Resumption of antiplatelet agents following intracerebral hemorrhage showed no evidence of increased risk of recurrent intracerebral hemorrhage or major hemorrhagic events.

Citation: RESTART Collaboration. Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): A randomized, open-label trial. Lancet. 2019. doi: 10.1016/S0140-6736(19)30840-2.

Dr. Deitelzweig is system department chair of hospital medicine at Ochsner Health System, New Orleans.

Background: Antiplatelet agents reduce the risk of major vascular events in patient with established vaso-occlusive disease, but they may increase the risk of ICH. Patients with prior ICH are at risk for both vaso-occlusive and hemorrhagic events. Clarification of the relative risk and benefit of antiplatelet agent use in this clinical scenario would serve to guide therapy.

Hospitalists should be aware that these data suggest that the risk assessment for resumption of antiplatelet agents should not be affected by a history of nontraumatic intracerebral hemorrhage when weighed against the benefit of these medications in patients with occlusive vascular disease.

Bottom line: Resumption of antiplatelet agents following intracerebral hemorrhage showed no evidence of increased risk of recurrent intracerebral hemorrhage or major hemorrhagic events.

Citation: RESTART Collaboration. Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): A randomized, open-label trial. Lancet. 2019. doi: 10.1016/S0140-6736(19)30840-2.

Dr. Deitelzweig is system department chair of hospital medicine at Ochsner Health System, New Orleans.

Systemic bevacizumab is safe and highly effective for the management of chronic bleeding and anemia in patients with hereditary hemorrhagic telangiectasia (HHT), according to findings from an international observational study.

In 238 patients from 12 international centers who were treated with bevacizumab for a median of 12 months, mean hemoglobin levels increased by 3.2 g/dL (mean pre- and posttreatment levels, 8.6 vs. 11.8 g/dL), and epistaxis severity scores (ESS) decreased by a mean of 3.4 points (pre- and posttreatment scores, 6.8 vs. 3.4 points), Hanny Al-Samkari, MD, reported at the International Society on Thrombosis and Haemostasis virtual congress.

As established in prior studies, the minimal clinically important difference in the ESS, a well-validated 10-point bleeding score in HHT, is 0.71 points; the mean reduction seen in this study was 4.75 times that, noted Dr. Al-Samkari, a clinical investigator and hematologist at Massachusetts General Hospital, Boston.

Further, the median number of red blood cell units transfused during the first year of treatment decreased by 82%, compared with the 6 months prior to treatment (9.0 vs. 0 units), and median iron infusions decreased by 70% during the same period (8.0 vs. 2.0 infusions), he said, adding that these improvements occurred within the first 6 months of treatment and were maintained through 12 months.

Study subjects were adults with a mean age of 63 years who were treated with systemic bevacizumab, a vascular endothelial growth factor receptor (VEGF) monoclonal antibody, between 2011 and 2019 for the primary indication of moderate to severe chronic HHT-related bleeding and anemia. Treatment involved four to eight induction infusions – typically at a dose of 5 mg/kg and given 4 weeks apart – followed by bevacizumab maintenance, either as continuous or scheduled maintenance at 4-, 8-, or 12-week intervals regardless of symptoms, or on an as-needed basis, with 2-6 infusions for signs or symptoms of rebleeding.

Patients received a median of 11 infusions, and 181 received maintenance treatment, including continuous or scheduled maintenance in 136 patients and as-needed maintenance in 45 patients, Dr. Al-Samkari said.

The treatment was generally well tolerated; the most common adverse events during 344 patient-years of treatment were hypertension, fatigue, and proteinuria. No fatal treatment-related adverse events occurred, and no increase in adverse events occurred with longer treatment, he noted

Venous thromboembolism occurred in five patients, including two patients who had “provoked events immediately following joint replacement surgery,” he said.

Thirteen patients (5%) discontinued treatment – 11 for inadequate effect and 2 for side effects, he noted.

Subgroup analyses showed that outcomes were similar regardless of underlying pathogenic mutation, but among those receiving bevacizumab maintenance, the continuous approach, compared with as-needed maintenance, was associated with greater improvement in hemoglobin (10.8 vs. 12.3 g/dL) and ESS (mean, 4.96 vs. 2.88) during months 7-12 of treatment, “which is the time most reflective of the effect of maintenance,” he said.

HHT, also known as Osler-Weber-Rendu disease, is a “rare, genetic, progressive, multisystem bleeding disorder resulting from disorder of angiogenesis,” Dr. Al-Samkari explained, adding that the condition is characterized by severe, recurrent epistaxis and chronic gastrointestinal bleeding.

“Bleeding frequently leads to iron deficiency anemia, which may be severe and dependent on regular iron infusions and/or blood transfusions,” he said.

Though rare, it is the second most common bleeding disorder worldwide, with a prevalence about twice that of hemophilia A and six times that of hemophilia B.

“Despite this, it has no FDA-approved therapies,” he said. “The current mainstay of care is surgical or procedural local hemostatic intervention – which is usually temporizing – and hematological support in the form of blood and iron.”

However, given that the underlying genetic defects that cause HHT result in elevations in VEGF, targeting VEGF with existing antiangiogenic agents is a promising approach.

In fact, several centers have been using bevacizumab for several years as an off-label treatment for bleeding in this setting, and while scattered case reports and small case series suggest efficacy, no “large or definitive studies” have been conducted, and safety hasn’t been carefully evaluated, he said.

To that end, the International Hereditary Hemorrhagic Telangiectasia Intravenous Bevacizumab Investigative Team (InHIBIT) was formed. The current report, “the largest study of antiangiogenic therapy to date in HHT,” represents the results of the InHIBIT-Bleed study, the first completed by the team. The next study will address bevacizumab for the treatment of high-output cardiac failure in HHT (the InHIBIT-HF study), Dr. Al-Samkari said.

Though limited by its retrospective nature and lack of a unified treatment protocol, the InHIBIT-Bleed study provides important information and is strengthened by the large cohort size, especially given that HHT is a rare disease, and by other factors, such as the substantial number of patient-years of treatment.

“Bevacizumab was effective in the management of severe HHT-related epistaxis and GI bleeds,” he said, noting the “significant and striking improvements” on a variety of measures.

Questioned about the durability of treatment effects after treatment discontinuation, Dr. Al-Samkari said outcomes are variable, “highly patient dependent,” and “something that we really need to investigate thoroughly.”

As for the potential for anti-VEGF therapy for bleeding in certain non-HHT settings, session moderator Michael Makris, MD, professor of haemostasis and thrombosis at the University of Sheffield, England, said the possibilities are intriguing.

“I work with lots of patients with von Willebrand disease and angiodysplasia,” he said, adding that angiodysplasia-related bleeding in type 2A von Willebrand disease is a major issue.

Dr. Al-Samkari agreed that the possibility is worth exploring.

“We have looked at this in a small number of patients, and the jury is still out,” he said. “But there is a publication in Gastroenterology – Albitar et al. – that evaluated bevacizumab in patients without HHT [who had] angiodysplasias from other causes – not specifically in type 2 von Willebrand syndrome ... and did find that it was effective at causing the angiodysplasias to regress, hemoglobin to improve.

“So the non-HHT use of this agent is certainly an important one [and] we do have retrospective evidence in a small group of patients who don’t have HHT, who do have angiodysplasias and bleeding, that it may be effective as well.”

Dr. Al-Samkari reported receiving research support and/or consulting fees from Agios, Amgen, and Dova.

sworcester@mdedge.com

SOURCE: Al-Samkari H et al. ISTH 2020, Abstract OC 09.2.

Systemic bevacizumab is safe and highly effective for the management of chronic bleeding and anemia in patients with hereditary hemorrhagic telangiectasia (HHT), according to findings from an international observational study.

In 238 patients from 12 international centers who were treated with bevacizumab for a median of 12 months, mean hemoglobin levels increased by 3.2 g/dL (mean pre- and posttreatment levels, 8.6 vs. 11.8 g/dL), and epistaxis severity scores (ESS) decreased by a mean of 3.4 points (pre- and posttreatment scores, 6.8 vs. 3.4 points), Hanny Al-Samkari, MD, reported at the International Society on Thrombosis and Haemostasis virtual congress.

As established in prior studies, the minimal clinically important difference in the ESS, a well-validated 10-point bleeding score in HHT, is 0.71 points; the mean reduction seen in this study was 4.75 times that, noted Dr. Al-Samkari, a clinical investigator and hematologist at Massachusetts General Hospital, Boston.

Further, the median number of red blood cell units transfused during the first year of treatment decreased by 82%, compared with the 6 months prior to treatment (9.0 vs. 0 units), and median iron infusions decreased by 70% during the same period (8.0 vs. 2.0 infusions), he said, adding that these improvements occurred within the first 6 months of treatment and were maintained through 12 months.

Study subjects were adults with a mean age of 63 years who were treated with systemic bevacizumab, a vascular endothelial growth factor receptor (VEGF) monoclonal antibody, between 2011 and 2019 for the primary indication of moderate to severe chronic HHT-related bleeding and anemia. Treatment involved four to eight induction infusions – typically at a dose of 5 mg/kg and given 4 weeks apart – followed by bevacizumab maintenance, either as continuous or scheduled maintenance at 4-, 8-, or 12-week intervals regardless of symptoms, or on an as-needed basis, with 2-6 infusions for signs or symptoms of rebleeding.

Patients received a median of 11 infusions, and 181 received maintenance treatment, including continuous or scheduled maintenance in 136 patients and as-needed maintenance in 45 patients, Dr. Al-Samkari said.

The treatment was generally well tolerated; the most common adverse events during 344 patient-years of treatment were hypertension, fatigue, and proteinuria. No fatal treatment-related adverse events occurred, and no increase in adverse events occurred with longer treatment, he noted

Venous thromboembolism occurred in five patients, including two patients who had “provoked events immediately following joint replacement surgery,” he said.

Thirteen patients (5%) discontinued treatment – 11 for inadequate effect and 2 for side effects, he noted.

Subgroup analyses showed that outcomes were similar regardless of underlying pathogenic mutation, but among those receiving bevacizumab maintenance, the continuous approach, compared with as-needed maintenance, was associated with greater improvement in hemoglobin (10.8 vs. 12.3 g/dL) and ESS (mean, 4.96 vs. 2.88) during months 7-12 of treatment, “which is the time most reflective of the effect of maintenance,” he said.

HHT, also known as Osler-Weber-Rendu disease, is a “rare, genetic, progressive, multisystem bleeding disorder resulting from disorder of angiogenesis,” Dr. Al-Samkari explained, adding that the condition is characterized by severe, recurrent epistaxis and chronic gastrointestinal bleeding.

“Bleeding frequently leads to iron deficiency anemia, which may be severe and dependent on regular iron infusions and/or blood transfusions,” he said.

Though rare, it is the second most common bleeding disorder worldwide, with a prevalence about twice that of hemophilia A and six times that of hemophilia B.

“Despite this, it has no FDA-approved therapies,” he said. “The current mainstay of care is surgical or procedural local hemostatic intervention – which is usually temporizing – and hematological support in the form of blood and iron.”

However, given that the underlying genetic defects that cause HHT result in elevations in VEGF, targeting VEGF with existing antiangiogenic agents is a promising approach.

In fact, several centers have been using bevacizumab for several years as an off-label treatment for bleeding in this setting, and while scattered case reports and small case series suggest efficacy, no “large or definitive studies” have been conducted, and safety hasn’t been carefully evaluated, he said.

To that end, the International Hereditary Hemorrhagic Telangiectasia Intravenous Bevacizumab Investigative Team (InHIBIT) was formed. The current report, “the largest study of antiangiogenic therapy to date in HHT,” represents the results of the InHIBIT-Bleed study, the first completed by the team. The next study will address bevacizumab for the treatment of high-output cardiac failure in HHT (the InHIBIT-HF study), Dr. Al-Samkari said.

Though limited by its retrospective nature and lack of a unified treatment protocol, the InHIBIT-Bleed study provides important information and is strengthened by the large cohort size, especially given that HHT is a rare disease, and by other factors, such as the substantial number of patient-years of treatment.

“Bevacizumab was effective in the management of severe HHT-related epistaxis and GI bleeds,” he said, noting the “significant and striking improvements” on a variety of measures.

Questioned about the durability of treatment effects after treatment discontinuation, Dr. Al-Samkari said outcomes are variable, “highly patient dependent,” and “something that we really need to investigate thoroughly.”

As for the potential for anti-VEGF therapy for bleeding in certain non-HHT settings, session moderator Michael Makris, MD, professor of haemostasis and thrombosis at the University of Sheffield, England, said the possibilities are intriguing.

“I work with lots of patients with von Willebrand disease and angiodysplasia,” he said, adding that angiodysplasia-related bleeding in type 2A von Willebrand disease is a major issue.

Dr. Al-Samkari agreed that the possibility is worth exploring.

“We have looked at this in a small number of patients, and the jury is still out,” he said. “But there is a publication in Gastroenterology – Albitar et al. – that evaluated bevacizumab in patients without HHT [who had] angiodysplasias from other causes – not specifically in type 2 von Willebrand syndrome ... and did find that it was effective at causing the angiodysplasias to regress, hemoglobin to improve.

“So the non-HHT use of this agent is certainly an important one [and] we do have retrospective evidence in a small group of patients who don’t have HHT, who do have angiodysplasias and bleeding, that it may be effective as well.”

Dr. Al-Samkari reported receiving research support and/or consulting fees from Agios, Amgen, and Dova.

sworcester@mdedge.com

SOURCE: Al-Samkari H et al. ISTH 2020, Abstract OC 09.2.

Systemic bevacizumab is safe and highly effective for the management of chronic bleeding and anemia in patients with hereditary hemorrhagic telangiectasia (HHT), according to findings from an international observational study.

In 238 patients from 12 international centers who were treated with bevacizumab for a median of 12 months, mean hemoglobin levels increased by 3.2 g/dL (mean pre- and posttreatment levels, 8.6 vs. 11.8 g/dL), and epistaxis severity scores (ESS) decreased by a mean of 3.4 points (pre- and posttreatment scores, 6.8 vs. 3.4 points), Hanny Al-Samkari, MD, reported at the International Society on Thrombosis and Haemostasis virtual congress.

As established in prior studies, the minimal clinically important difference in the ESS, a well-validated 10-point bleeding score in HHT, is 0.71 points; the mean reduction seen in this study was 4.75 times that, noted Dr. Al-Samkari, a clinical investigator and hematologist at Massachusetts General Hospital, Boston.

Further, the median number of red blood cell units transfused during the first year of treatment decreased by 82%, compared with the 6 months prior to treatment (9.0 vs. 0 units), and median iron infusions decreased by 70% during the same period (8.0 vs. 2.0 infusions), he said, adding that these improvements occurred within the first 6 months of treatment and were maintained through 12 months.

Study subjects were adults with a mean age of 63 years who were treated with systemic bevacizumab, a vascular endothelial growth factor receptor (VEGF) monoclonal antibody, between 2011 and 2019 for the primary indication of moderate to severe chronic HHT-related bleeding and anemia. Treatment involved four to eight induction infusions – typically at a dose of 5 mg/kg and given 4 weeks apart – followed by bevacizumab maintenance, either as continuous or scheduled maintenance at 4-, 8-, or 12-week intervals regardless of symptoms, or on an as-needed basis, with 2-6 infusions for signs or symptoms of rebleeding.

Patients received a median of 11 infusions, and 181 received maintenance treatment, including continuous or scheduled maintenance in 136 patients and as-needed maintenance in 45 patients, Dr. Al-Samkari said.

The treatment was generally well tolerated; the most common adverse events during 344 patient-years of treatment were hypertension, fatigue, and proteinuria. No fatal treatment-related adverse events occurred, and no increase in adverse events occurred with longer treatment, he noted

Venous thromboembolism occurred in five patients, including two patients who had “provoked events immediately following joint replacement surgery,” he said.

Thirteen patients (5%) discontinued treatment – 11 for inadequate effect and 2 for side effects, he noted.

Subgroup analyses showed that outcomes were similar regardless of underlying pathogenic mutation, but among those receiving bevacizumab maintenance, the continuous approach, compared with as-needed maintenance, was associated with greater improvement in hemoglobin (10.8 vs. 12.3 g/dL) and ESS (mean, 4.96 vs. 2.88) during months 7-12 of treatment, “which is the time most reflective of the effect of maintenance,” he said.

HHT, also known as Osler-Weber-Rendu disease, is a “rare, genetic, progressive, multisystem bleeding disorder resulting from disorder of angiogenesis,” Dr. Al-Samkari explained, adding that the condition is characterized by severe, recurrent epistaxis and chronic gastrointestinal bleeding.

“Bleeding frequently leads to iron deficiency anemia, which may be severe and dependent on regular iron infusions and/or blood transfusions,” he said.

Though rare, it is the second most common bleeding disorder worldwide, with a prevalence about twice that of hemophilia A and six times that of hemophilia B.

“Despite this, it has no FDA-approved therapies,” he said. “The current mainstay of care is surgical or procedural local hemostatic intervention – which is usually temporizing – and hematological support in the form of blood and iron.”

However, given that the underlying genetic defects that cause HHT result in elevations in VEGF, targeting VEGF with existing antiangiogenic agents is a promising approach.

In fact, several centers have been using bevacizumab for several years as an off-label treatment for bleeding in this setting, and while scattered case reports and small case series suggest efficacy, no “large or definitive studies” have been conducted, and safety hasn’t been carefully evaluated, he said.

To that end, the International Hereditary Hemorrhagic Telangiectasia Intravenous Bevacizumab Investigative Team (InHIBIT) was formed. The current report, “the largest study of antiangiogenic therapy to date in HHT,” represents the results of the InHIBIT-Bleed study, the first completed by the team. The next study will address bevacizumab for the treatment of high-output cardiac failure in HHT (the InHIBIT-HF study), Dr. Al-Samkari said.

Though limited by its retrospective nature and lack of a unified treatment protocol, the InHIBIT-Bleed study provides important information and is strengthened by the large cohort size, especially given that HHT is a rare disease, and by other factors, such as the substantial number of patient-years of treatment.

“Bevacizumab was effective in the management of severe HHT-related epistaxis and GI bleeds,” he said, noting the “significant and striking improvements” on a variety of measures.

Questioned about the durability of treatment effects after treatment discontinuation, Dr. Al-Samkari said outcomes are variable, “highly patient dependent,” and “something that we really need to investigate thoroughly.”

As for the potential for anti-VEGF therapy for bleeding in certain non-HHT settings, session moderator Michael Makris, MD, professor of haemostasis and thrombosis at the University of Sheffield, England, said the possibilities are intriguing.

“I work with lots of patients with von Willebrand disease and angiodysplasia,” he said, adding that angiodysplasia-related bleeding in type 2A von Willebrand disease is a major issue.

Dr. Al-Samkari agreed that the possibility is worth exploring.

“We have looked at this in a small number of patients, and the jury is still out,” he said. “But there is a publication in Gastroenterology – Albitar et al. – that evaluated bevacizumab in patients without HHT [who had] angiodysplasias from other causes – not specifically in type 2 von Willebrand syndrome ... and did find that it was effective at causing the angiodysplasias to regress, hemoglobin to improve.

“So the non-HHT use of this agent is certainly an important one [and] we do have retrospective evidence in a small group of patients who don’t have HHT, who do have angiodysplasias and bleeding, that it may be effective as well.”

Dr. Al-Samkari reported receiving research support and/or consulting fees from Agios, Amgen, and Dova.

sworcester@mdedge.com

SOURCE: Al-Samkari H et al. ISTH 2020, Abstract OC 09.2.

While SARS-CoV-2 causes frequent and potentially severe pulmonary disease, extrapulmonary manifestations may be a prominent part of the clinical spectrum, according to a review published in Nature Medicine.

In this comprehensive literature review, Aakriti Gupta, MD, of New York-Presbyterian/Columbia University Irving Medical Center and colleagues detailed the epidemiologic and clinical multisystem effects of COVID-19. The authors explained what is known and/or suspected about the pathophysiology of those effects and outlined the resultant management considerations.

Key mechanisms for multiorgan injury include direct viral toxicity, endothelial cell damage with inflammatory mediation of thrombosis, aberrant immune response, and dysregulation of the renin-angiotensin-aldosterone system.

The relative importance of each pathway in the clinical presentation of COVID-19 and the mechanism for extrapulmonary spread of SARS-CoV-2 infection are imperfectly understood, Dr. Gupta and colleagues noted.

As for the hematologic effects of COVID-19, patients may present with several laboratory abnormalities, but the most clinically relevant complications are thromboembolic.
 

COVID-19-associated coagulopathy

Dr. Gupta and colleagues noted that COVID-19–associated coagulopathy (CAC) is accompanied by elevated levels of D-dimer and fibrinogen, with minor abnormalities in prothrombin time, activated partial thromboplastin time, and platelet counts in the initial stage of infection.

Elevated D-dimer levels have been reported in up to 46% of hospitalized patients, and a longitudinal increase while hospitalized is associated with higher mortality.

In initial reports from China and the Netherlands, thrombotic complications were seen in up to 30% of COVID-19 patients in ICUs. Thromboembolic events have been reported in 17%-22% of critically ill COVID-19 patients in studies from Italy and France.

Globally, in severely affected COVID-19 patients, there have been reports of thromboses in intravenous catheters and extracorporeal circuits as well as arterial vascular occlusive events, including myocardial infarction, acute limb ischemia, and stroke.

There have been multiple small studies in which critically ill COVID-19 patients were routinely screened for thrombotic disease. In these studies, rates of thrombotic complications ranged from 69% to 85%, despite thromboprophylaxis. Variability in prophylactic and screening protocols explain discrepancies in event rates.
 

Pathophysiology

The abnormally high blood levels of D-dimer and fibrinogen during the early stages of SARS-CoV-2 infection are reflective of excessive inflammation rather than overt disseminated intravascular coagulation (DIC), which may develop in later stages of illness, according to Dr. Gupta and colleagues. The authors theorized that uninhibited inflammation, along with hypoxia and direct viral-mediated cellular injury, contribute to thrombotic complications in COVID-19 patients.

“The increased expression of ACE2 in endothelial cells after infection with SARS-CoV-2 may perpetuate a vicious cycle of endothelialitis that promotes thromboinflammation,” the authors wrote. “Collectively, hemostatic and inflammatory changes, which reflect endothelial damage and activation as well as critical illness, constitute a prothrombotic milieu.”

The authors noted that small autopsy series have shown high rates of microvascular and macrovascular thromboses, particularly in the pulmonary circulation, in COVID-19 patients.
 

Management considerations

Dr. Gupta and colleagues referenced interim guidelines from the International Society of Thrombosis and Haemostasis that recommend serial complete blood counts, with white blood cell differential and assessment of D-dimer, prothrombin time, and fibrinogen for hospitalized patients with COVID-19. The authors also cited guidelines published in the Journal of the American College of Cardiology that recommend routine risk assessment for venous thromboembolism in all hospitalized patients with COVID-19 and the consideration of standard-dose pharmaco-prophylaxis in patients who lack absolute contraindications.

Empiric use of higher-than-routine prophylactic-dose or therapeutic-dose anticoagulation in ICU patients in the absence of proven thromboses has been implemented in some institutions, Dr. Gupta and colleagues noted. Parenteral anticoagulants (such as low-molecular-weight or unfractionated heparin) are preferred to oral anticoagulants because of short half-life, available reversal agents, and the potential for drug interactions between oral agents and antiviral and/or antibacterial treatment, according to the authors.

They wrote that randomized clinical trials “will be crucial to establishing effective and safe strategies” for anticoagulation in COVID-19 patients. To this point, few randomized trials have been published to guide management of COVID-19–associated extrapulmonary manifestations, including CAC.
 

Research priorities

A more complete understanding of the organ-specific pathophysiology of this multisystem disease is vital, according to Dr. Gupta and colleagues.

“Regional, national, and international collaborations of clinicians and scientists focused on high-quality, transparent, ethical, and evidence-based research practices would help propel the global community toward achieving success against this pandemic,” the authors wrote.

They noted that common definitions and data standards for research are key for cross-institutional and international collaborations.

Initial attention to high-quality prospective scientific documentation standards would have been valuable and will be required for dedicated trials to address the multisystem effects of COVID-19.
 

Community of learners

As much as at any prior time in their careers, during the COVID-19 pandemic, health care providers have been enveloped in a community of learners – a group of people who share values and beliefs and who actively engage in learning from one another.

Through a patchwork of sources – news media, social media, traditional medical journals, general and COVID-focused meetings, and, most importantly, patients – we have been living in a learning-centered environment. Academicians, clinicians, practicing physicians, researchers, patients, family members, and caregivers have been actively and intentionally building a knowledge base together.

Through their published review, Dr. Gupta and colleagues have contributed meaningfully to the understanding our learning community has of the various extrapulmonary manifestations of COVID-19. The authors have provided a nice template for further research and clinical advances.

Dr. Gupta and colleagues disclosed financial relationships with a range of pharmaceutical companies and other organizations.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Source: Gupta A et al. Nat Med. 2020 Jul;26(7):1017-32.

While SARS-CoV-2 causes frequent and potentially severe pulmonary disease, extrapulmonary manifestations may be a prominent part of the clinical spectrum, according to a review published in Nature Medicine.

In this comprehensive literature review, Aakriti Gupta, MD, of New York-Presbyterian/Columbia University Irving Medical Center and colleagues detailed the epidemiologic and clinical multisystem effects of COVID-19. The authors explained what is known and/or suspected about the pathophysiology of those effects and outlined the resultant management considerations.

Key mechanisms for multiorgan injury include direct viral toxicity, endothelial cell damage with inflammatory mediation of thrombosis, aberrant immune response, and dysregulation of the renin-angiotensin-aldosterone system.

The relative importance of each pathway in the clinical presentation of COVID-19 and the mechanism for extrapulmonary spread of SARS-CoV-2 infection are imperfectly understood, Dr. Gupta and colleagues noted.

As for the hematologic effects of COVID-19, patients may present with several laboratory abnormalities, but the most clinically relevant complications are thromboembolic.
 

COVID-19-associated coagulopathy

Dr. Gupta and colleagues noted that COVID-19–associated coagulopathy (CAC) is accompanied by elevated levels of D-dimer and fibrinogen, with minor abnormalities in prothrombin time, activated partial thromboplastin time, and platelet counts in the initial stage of infection.

Elevated D-dimer levels have been reported in up to 46% of hospitalized patients, and a longitudinal increase while hospitalized is associated with higher mortality.

In initial reports from China and the Netherlands, thrombotic complications were seen in up to 30% of COVID-19 patients in ICUs. Thromboembolic events have been reported in 17%-22% of critically ill COVID-19 patients in studies from Italy and France.

Globally, in severely affected COVID-19 patients, there have been reports of thromboses in intravenous catheters and extracorporeal circuits as well as arterial vascular occlusive events, including myocardial infarction, acute limb ischemia, and stroke.

There have been multiple small studies in which critically ill COVID-19 patients were routinely screened for thrombotic disease. In these studies, rates of thrombotic complications ranged from 69% to 85%, despite thromboprophylaxis. Variability in prophylactic and screening protocols explain discrepancies in event rates.
 

Pathophysiology

The abnormally high blood levels of D-dimer and fibrinogen during the early stages of SARS-CoV-2 infection are reflective of excessive inflammation rather than overt disseminated intravascular coagulation (DIC), which may develop in later stages of illness, according to Dr. Gupta and colleagues. The authors theorized that uninhibited inflammation, along with hypoxia and direct viral-mediated cellular injury, contribute to thrombotic complications in COVID-19 patients.

“The increased expression of ACE2 in endothelial cells after infection with SARS-CoV-2 may perpetuate a vicious cycle of endothelialitis that promotes thromboinflammation,” the authors wrote. “Collectively, hemostatic and inflammatory changes, which reflect endothelial damage and activation as well as critical illness, constitute a prothrombotic milieu.”

The authors noted that small autopsy series have shown high rates of microvascular and macrovascular thromboses, particularly in the pulmonary circulation, in COVID-19 patients.
 

Management considerations

Dr. Gupta and colleagues referenced interim guidelines from the International Society of Thrombosis and Haemostasis that recommend serial complete blood counts, with white blood cell differential and assessment of D-dimer, prothrombin time, and fibrinogen for hospitalized patients with COVID-19. The authors also cited guidelines published in the Journal of the American College of Cardiology that recommend routine risk assessment for venous thromboembolism in all hospitalized patients with COVID-19 and the consideration of standard-dose pharmaco-prophylaxis in patients who lack absolute contraindications.

Empiric use of higher-than-routine prophylactic-dose or therapeutic-dose anticoagulation in ICU patients in the absence of proven thromboses has been implemented in some institutions, Dr. Gupta and colleagues noted. Parenteral anticoagulants (such as low-molecular-weight or unfractionated heparin) are preferred to oral anticoagulants because of short half-life, available reversal agents, and the potential for drug interactions between oral agents and antiviral and/or antibacterial treatment, according to the authors.

They wrote that randomized clinical trials “will be crucial to establishing effective and safe strategies” for anticoagulation in COVID-19 patients. To this point, few randomized trials have been published to guide management of COVID-19–associated extrapulmonary manifestations, including CAC.
 

Research priorities

A more complete understanding of the organ-specific pathophysiology of this multisystem disease is vital, according to Dr. Gupta and colleagues.

“Regional, national, and international collaborations of clinicians and scientists focused on high-quality, transparent, ethical, and evidence-based research practices would help propel the global community toward achieving success against this pandemic,” the authors wrote.

They noted that common definitions and data standards for research are key for cross-institutional and international collaborations.

Initial attention to high-quality prospective scientific documentation standards would have been valuable and will be required for dedicated trials to address the multisystem effects of COVID-19.
 

Community of learners

As much as at any prior time in their careers, during the COVID-19 pandemic, health care providers have been enveloped in a community of learners – a group of people who share values and beliefs and who actively engage in learning from one another.

Through a patchwork of sources – news media, social media, traditional medical journals, general and COVID-focused meetings, and, most importantly, patients – we have been living in a learning-centered environment. Academicians, clinicians, practicing physicians, researchers, patients, family members, and caregivers have been actively and intentionally building a knowledge base together.

Through their published review, Dr. Gupta and colleagues have contributed meaningfully to the understanding our learning community has of the various extrapulmonary manifestations of COVID-19. The authors have provided a nice template for further research and clinical advances.

Dr. Gupta and colleagues disclosed financial relationships with a range of pharmaceutical companies and other organizations.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Source: Gupta A et al. Nat Med. 2020 Jul;26(7):1017-32.

While SARS-CoV-2 causes frequent and potentially severe pulmonary disease, extrapulmonary manifestations may be a prominent part of the clinical spectrum, according to a review published in Nature Medicine.

In this comprehensive literature review, Aakriti Gupta, MD, of New York-Presbyterian/Columbia University Irving Medical Center and colleagues detailed the epidemiologic and clinical multisystem effects of COVID-19. The authors explained what is known and/or suspected about the pathophysiology of those effects and outlined the resultant management considerations.

Key mechanisms for multiorgan injury include direct viral toxicity, endothelial cell damage with inflammatory mediation of thrombosis, aberrant immune response, and dysregulation of the renin-angiotensin-aldosterone system.

The relative importance of each pathway in the clinical presentation of COVID-19 and the mechanism for extrapulmonary spread of SARS-CoV-2 infection are imperfectly understood, Dr. Gupta and colleagues noted.

As for the hematologic effects of COVID-19, patients may present with several laboratory abnormalities, but the most clinically relevant complications are thromboembolic.
 

COVID-19-associated coagulopathy

Dr. Gupta and colleagues noted that COVID-19–associated coagulopathy (CAC) is accompanied by elevated levels of D-dimer and fibrinogen, with minor abnormalities in prothrombin time, activated partial thromboplastin time, and platelet counts in the initial stage of infection.

Elevated D-dimer levels have been reported in up to 46% of hospitalized patients, and a longitudinal increase while hospitalized is associated with higher mortality.

In initial reports from China and the Netherlands, thrombotic complications were seen in up to 30% of COVID-19 patients in ICUs. Thromboembolic events have been reported in 17%-22% of critically ill COVID-19 patients in studies from Italy and France.

Globally, in severely affected COVID-19 patients, there have been reports of thromboses in intravenous catheters and extracorporeal circuits as well as arterial vascular occlusive events, including myocardial infarction, acute limb ischemia, and stroke.

There have been multiple small studies in which critically ill COVID-19 patients were routinely screened for thrombotic disease. In these studies, rates of thrombotic complications ranged from 69% to 85%, despite thromboprophylaxis. Variability in prophylactic and screening protocols explain discrepancies in event rates.
 

Pathophysiology

The abnormally high blood levels of D-dimer and fibrinogen during the early stages of SARS-CoV-2 infection are reflective of excessive inflammation rather than overt disseminated intravascular coagulation (DIC), which may develop in later stages of illness, according to Dr. Gupta and colleagues. The authors theorized that uninhibited inflammation, along with hypoxia and direct viral-mediated cellular injury, contribute to thrombotic complications in COVID-19 patients.

“The increased expression of ACE2 in endothelial cells after infection with SARS-CoV-2 may perpetuate a vicious cycle of endothelialitis that promotes thromboinflammation,” the authors wrote. “Collectively, hemostatic and inflammatory changes, which reflect endothelial damage and activation as well as critical illness, constitute a prothrombotic milieu.”

The authors noted that small autopsy series have shown high rates of microvascular and macrovascular thromboses, particularly in the pulmonary circulation, in COVID-19 patients.
 

Management considerations

Dr. Gupta and colleagues referenced interim guidelines from the International Society of Thrombosis and Haemostasis that recommend serial complete blood counts, with white blood cell differential and assessment of D-dimer, prothrombin time, and fibrinogen for hospitalized patients with COVID-19. The authors also cited guidelines published in the Journal of the American College of Cardiology that recommend routine risk assessment for venous thromboembolism in all hospitalized patients with COVID-19 and the consideration of standard-dose pharmaco-prophylaxis in patients who lack absolute contraindications.

Empiric use of higher-than-routine prophylactic-dose or therapeutic-dose anticoagulation in ICU patients in the absence of proven thromboses has been implemented in some institutions, Dr. Gupta and colleagues noted. Parenteral anticoagulants (such as low-molecular-weight or unfractionated heparin) are preferred to oral anticoagulants because of short half-life, available reversal agents, and the potential for drug interactions between oral agents and antiviral and/or antibacterial treatment, according to the authors.

They wrote that randomized clinical trials “will be crucial to establishing effective and safe strategies” for anticoagulation in COVID-19 patients. To this point, few randomized trials have been published to guide management of COVID-19–associated extrapulmonary manifestations, including CAC.
 

Research priorities

A more complete understanding of the organ-specific pathophysiology of this multisystem disease is vital, according to Dr. Gupta and colleagues.

“Regional, national, and international collaborations of clinicians and scientists focused on high-quality, transparent, ethical, and evidence-based research practices would help propel the global community toward achieving success against this pandemic,” the authors wrote.

They noted that common definitions and data standards for research are key for cross-institutional and international collaborations.

Initial attention to high-quality prospective scientific documentation standards would have been valuable and will be required for dedicated trials to address the multisystem effects of COVID-19.
 

Community of learners

As much as at any prior time in their careers, during the COVID-19 pandemic, health care providers have been enveloped in a community of learners – a group of people who share values and beliefs and who actively engage in learning from one another.

Through a patchwork of sources – news media, social media, traditional medical journals, general and COVID-focused meetings, and, most importantly, patients – we have been living in a learning-centered environment. Academicians, clinicians, practicing physicians, researchers, patients, family members, and caregivers have been actively and intentionally building a knowledge base together.

Through their published review, Dr. Gupta and colleagues have contributed meaningfully to the understanding our learning community has of the various extrapulmonary manifestations of COVID-19. The authors have provided a nice template for further research and clinical advances.

Dr. Gupta and colleagues disclosed financial relationships with a range of pharmaceutical companies and other organizations.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Source: Gupta A et al. Nat Med. 2020 Jul;26(7):1017-32.