Atlanta – Adding caplacizumab, an anti–Von Willebrand Factor humanized single variable domain immunoglobulin, to standard therapy for acquired thrombotic thrombocytopenic purpura (aTTP) significantly hastened platelet normalization and improved several key clinical endpoints in a pivotal randomized placebo-controlled phase 3 trial of 145 patients (HERCULES).

At any given time, platelet normalization was 55% more likely with caplacizumab (10 mg) versus placebo (platelet normalization rate ratio, 1.55; 95% confidence interval, 1.10-2.20; P less than .01), Marie Scully, MD, reported in late-breaking oral presentation at the annual meeting of the American Society for Hematology.Caplacizumab also significantly reduced the rate of aTTP recurrence, compared with placebo (13% vs. 38%; P less than .001) and cut days of plasma exchange, plasma volume, and ICU and hospital stays by 31% to 65%, compared with placebo, reported Dr. Scully of University College Hospital, London, UK. HERCULES enrolled patients with an acute episode of aTTP and at least one prior plasma exchange (PE). Patients received caplacizumab (10 mg) or placebo plus daily PE plus corticosteroids. The caplacizumab group received a single IV dose before their first on-study PE followed by daily subcutaneous doses during PE therapy and for 30 days afterward.

Phase 2 data on aTTP earned caplacizumab fast track designation from the Food and Drug Administration in July 2017. In this video, Dr. Scully highlights key findings of the phase 3 HERCULES trial and discusses how physicians could integrate caplacizumab into their current aTTP treatment approach.

HERCULES was sponsored by Ablynx. Dr. Scully disclosed honoraria and research funding from Ablynx, Shire, Novartis, and Alexion.

Atlanta – Adding caplacizumab, an anti–Von Willebrand Factor humanized single variable domain immunoglobulin, to standard therapy for acquired thrombotic thrombocytopenic purpura (aTTP) significantly hastened platelet normalization and improved several key clinical endpoints in a pivotal randomized placebo-controlled phase 3 trial of 145 patients (HERCULES).

At any given time, platelet normalization was 55% more likely with caplacizumab (10 mg) versus placebo (platelet normalization rate ratio, 1.55; 95% confidence interval, 1.10-2.20; P less than .01), Marie Scully, MD, reported in late-breaking oral presentation at the annual meeting of the American Society for Hematology.Caplacizumab also significantly reduced the rate of aTTP recurrence, compared with placebo (13% vs. 38%; P less than .001) and cut days of plasma exchange, plasma volume, and ICU and hospital stays by 31% to 65%, compared with placebo, reported Dr. Scully of University College Hospital, London, UK. HERCULES enrolled patients with an acute episode of aTTP and at least one prior plasma exchange (PE). Patients received caplacizumab (10 mg) or placebo plus daily PE plus corticosteroids. The caplacizumab group received a single IV dose before their first on-study PE followed by daily subcutaneous doses during PE therapy and for 30 days afterward.

Phase 2 data on aTTP earned caplacizumab fast track designation from the Food and Drug Administration in July 2017. In this video, Dr. Scully highlights key findings of the phase 3 HERCULES trial and discusses how physicians could integrate caplacizumab into their current aTTP treatment approach.

HERCULES was sponsored by Ablynx. Dr. Scully disclosed honoraria and research funding from Ablynx, Shire, Novartis, and Alexion.

Atlanta – Adding caplacizumab, an anti–Von Willebrand Factor humanized single variable domain immunoglobulin, to standard therapy for acquired thrombotic thrombocytopenic purpura (aTTP) significantly hastened platelet normalization and improved several key clinical endpoints in a pivotal randomized placebo-controlled phase 3 trial of 145 patients (HERCULES).

At any given time, platelet normalization was 55% more likely with caplacizumab (10 mg) versus placebo (platelet normalization rate ratio, 1.55; 95% confidence interval, 1.10-2.20; P less than .01), Marie Scully, MD, reported in late-breaking oral presentation at the annual meeting of the American Society for Hematology.Caplacizumab also significantly reduced the rate of aTTP recurrence, compared with placebo (13% vs. 38%; P less than .001) and cut days of plasma exchange, plasma volume, and ICU and hospital stays by 31% to 65%, compared with placebo, reported Dr. Scully of University College Hospital, London, UK. HERCULES enrolled patients with an acute episode of aTTP and at least one prior plasma exchange (PE). Patients received caplacizumab (10 mg) or placebo plus daily PE plus corticosteroids. The caplacizumab group received a single IV dose before their first on-study PE followed by daily subcutaneous doses during PE therapy and for 30 days afterward.

Phase 2 data on aTTP earned caplacizumab fast track designation from the Food and Drug Administration in July 2017. In this video, Dr. Scully highlights key findings of the phase 3 HERCULES trial and discusses how physicians could integrate caplacizumab into their current aTTP treatment approach.

HERCULES was sponsored by Ablynx. Dr. Scully disclosed honoraria and research funding from Ablynx, Shire, Novartis, and Alexion.

SAN DIEGO – After funding was discontinued for individual donation (ID) nucleic acid testing (NAT) of blood donations, the risk of transfusion-related infections in Denmark increased. But according to new findings presented here at the American Association of Blood Banks annual meeting, that policy was short lived.

When ID NAT was removed from the screening process, the estimated increase in the risk for transfusion-transmitted HIV went from one in 80 years to one in 18 years; for hepatitis B virus (HBV), it went from one in 34 years to one in 17 years; and for hepatitis C virus (HCV), the risk increased from one in 250 years to one in 8 years.

“Between 2009 and 2016, we had 14 NAT reactive/seronegative cases among the repeat donors, and one was due to an acute hepatitis C infection,” said study author Leen Baudewijn, MD, of Odense (Denmark) University Hospital. “This would have been missed without NAT testing.”

Dr. Baudewijn explained that Denmark has since reversed this new policy. “The Danish government decided not to discontinue NAT because there were almost no savings,” she said during her presentation. “We had the extra costs for anti-HBc [anti-Hepatitis B core] testing for repeat donors, and extra cost due to mandatory NAT testing for plasma for manufacturing medicinal products. So it was not possible to abrogate NAT testing because of contracts with the industry.”

However, she added that “one of the most important reasons was that one of the vendors for NAT screening reduced the price substantially by 45%.”

The majority of industrialized countries have implemented the use of increasingly sensitive assays for screening donated blood, although to date, there is no technology that can guarantee zero-risk blood products. However, the risk for transmission of a viral infection via transfusion is low in Northern Europe.

But after a case of HIV infection linked to a blood transfusion occurred, Denmark mandated ID NAT in 2009 for serologic-based screening assays for HIV, HBV, and HCV. In July 2017, the government changed its policy and discontinued funding for ID NAT screening and, instead, mandated anti-Hepatitis B core screening be added to the serologic screening assays for repeat donors.

In this study, Dr. Baudewijn and her colleagues used an incidence/window model to estimate the residual risk (RR) of transfusion-transmitted viral infections after ID NAT was halted in Denmark. They estimated incidence rates for blood and plasma donations obtained from repeat donors during 2006-2016 based on the number of positive tests after a negative donation. The residual risk was estimated as the incidence rate multiplied by the average window period for HIV, HBV, and HCV, with and without ID NAT testing.

A total of 3.5 million donations were screened during the study’s time period, with donors averaging two blood donations per year. The researchers estimated the RR for each donation with and without ID NAT.

For HIV, the RR without ID NAT was 1/3,647,888 and with ID NAT it was 1/16,436,213; for HBV, those numbers were 1/3,352,628 without and 1/6,806,407 with; and for HCV, 1/1,573,213 without and 1/50,429,289, with.

The overall probability of missing an infectious red blood cell unit was 35/1,000 in a population of 6 million, Dr. Baudewijn noted.

The authors had no relevant financial disclosures

SOURCE: Baudewijn L et al. AABB 2017. Abstract P4-A03A.

SAN DIEGO – After funding was discontinued for individual donation (ID) nucleic acid testing (NAT) of blood donations, the risk of transfusion-related infections in Denmark increased. But according to new findings presented here at the American Association of Blood Banks annual meeting, that policy was short lived.

When ID NAT was removed from the screening process, the estimated increase in the risk for transfusion-transmitted HIV went from one in 80 years to one in 18 years; for hepatitis B virus (HBV), it went from one in 34 years to one in 17 years; and for hepatitis C virus (HCV), the risk increased from one in 250 years to one in 8 years.

“Between 2009 and 2016, we had 14 NAT reactive/seronegative cases among the repeat donors, and one was due to an acute hepatitis C infection,” said study author Leen Baudewijn, MD, of Odense (Denmark) University Hospital. “This would have been missed without NAT testing.”

Dr. Baudewijn explained that Denmark has since reversed this new policy. “The Danish government decided not to discontinue NAT because there were almost no savings,” she said during her presentation. “We had the extra costs for anti-HBc [anti-Hepatitis B core] testing for repeat donors, and extra cost due to mandatory NAT testing for plasma for manufacturing medicinal products. So it was not possible to abrogate NAT testing because of contracts with the industry.”

However, she added that “one of the most important reasons was that one of the vendors for NAT screening reduced the price substantially by 45%.”

The majority of industrialized countries have implemented the use of increasingly sensitive assays for screening donated blood, although to date, there is no technology that can guarantee zero-risk blood products. However, the risk for transmission of a viral infection via transfusion is low in Northern Europe.

But after a case of HIV infection linked to a blood transfusion occurred, Denmark mandated ID NAT in 2009 for serologic-based screening assays for HIV, HBV, and HCV. In July 2017, the government changed its policy and discontinued funding for ID NAT screening and, instead, mandated anti-Hepatitis B core screening be added to the serologic screening assays for repeat donors.

In this study, Dr. Baudewijn and her colleagues used an incidence/window model to estimate the residual risk (RR) of transfusion-transmitted viral infections after ID NAT was halted in Denmark. They estimated incidence rates for blood and plasma donations obtained from repeat donors during 2006-2016 based on the number of positive tests after a negative donation. The residual risk was estimated as the incidence rate multiplied by the average window period for HIV, HBV, and HCV, with and without ID NAT testing.

A total of 3.5 million donations were screened during the study’s time period, with donors averaging two blood donations per year. The researchers estimated the RR for each donation with and without ID NAT.

For HIV, the RR without ID NAT was 1/3,647,888 and with ID NAT it was 1/16,436,213; for HBV, those numbers were 1/3,352,628 without and 1/6,806,407 with; and for HCV, 1/1,573,213 without and 1/50,429,289, with.

The overall probability of missing an infectious red blood cell unit was 35/1,000 in a population of 6 million, Dr. Baudewijn noted.

The authors had no relevant financial disclosures

SOURCE: Baudewijn L et al. AABB 2017. Abstract P4-A03A.

SAN DIEGO – After funding was discontinued for individual donation (ID) nucleic acid testing (NAT) of blood donations, the risk of transfusion-related infections in Denmark increased. But according to new findings presented here at the American Association of Blood Banks annual meeting, that policy was short lived.

When ID NAT was removed from the screening process, the estimated increase in the risk for transfusion-transmitted HIV went from one in 80 years to one in 18 years; for hepatitis B virus (HBV), it went from one in 34 years to one in 17 years; and for hepatitis C virus (HCV), the risk increased from one in 250 years to one in 8 years.

“Between 2009 and 2016, we had 14 NAT reactive/seronegative cases among the repeat donors, and one was due to an acute hepatitis C infection,” said study author Leen Baudewijn, MD, of Odense (Denmark) University Hospital. “This would have been missed without NAT testing.”

Dr. Baudewijn explained that Denmark has since reversed this new policy. “The Danish government decided not to discontinue NAT because there were almost no savings,” she said during her presentation. “We had the extra costs for anti-HBc [anti-Hepatitis B core] testing for repeat donors, and extra cost due to mandatory NAT testing for plasma for manufacturing medicinal products. So it was not possible to abrogate NAT testing because of contracts with the industry.”

However, she added that “one of the most important reasons was that one of the vendors for NAT screening reduced the price substantially by 45%.”

The majority of industrialized countries have implemented the use of increasingly sensitive assays for screening donated blood, although to date, there is no technology that can guarantee zero-risk blood products. However, the risk for transmission of a viral infection via transfusion is low in Northern Europe.

But after a case of HIV infection linked to a blood transfusion occurred, Denmark mandated ID NAT in 2009 for serologic-based screening assays for HIV, HBV, and HCV. In July 2017, the government changed its policy and discontinued funding for ID NAT screening and, instead, mandated anti-Hepatitis B core screening be added to the serologic screening assays for repeat donors.

In this study, Dr. Baudewijn and her colleagues used an incidence/window model to estimate the residual risk (RR) of transfusion-transmitted viral infections after ID NAT was halted in Denmark. They estimated incidence rates for blood and plasma donations obtained from repeat donors during 2006-2016 based on the number of positive tests after a negative donation. The residual risk was estimated as the incidence rate multiplied by the average window period for HIV, HBV, and HCV, with and without ID NAT testing.

A total of 3.5 million donations were screened during the study’s time period, with donors averaging two blood donations per year. The researchers estimated the RR for each donation with and without ID NAT.

For HIV, the RR without ID NAT was 1/3,647,888 and with ID NAT it was 1/16,436,213; for HBV, those numbers were 1/3,352,628 without and 1/6,806,407 with; and for HCV, 1/1,573,213 without and 1/50,429,289, with.

The overall probability of missing an infectious red blood cell unit was 35/1,000 in a population of 6 million, Dr. Baudewijn noted.

The authors had no relevant financial disclosures

SOURCE: Baudewijn L et al. AABB 2017. Abstract P4-A03A.

The Food and Drug Administration has given the nod to the first nebulized long-acting muscarinic antagonist (LAMA) treatment for chronic obstructive pulmonary disease (COPD) in the United States.

This product, glycopyrrolate, has specifically been approved for use as a long-term maintenance treatment of air-flow obstruction in patients with COPD. Glycopyrrolate (Lonhala Magnair) utilizes the eFlow technology system, developed by Pari Pharma. This nebulizing system is portable, virtually silent, and delivers the drug in 2-3 minutes, according to a statement from Sunovion Pharmaceuticals.

[email protected]

The Food and Drug Administration has given the nod to the first nebulized long-acting muscarinic antagonist (LAMA) treatment for chronic obstructive pulmonary disease (COPD) in the United States.

This product, glycopyrrolate, has specifically been approved for use as a long-term maintenance treatment of air-flow obstruction in patients with COPD. Glycopyrrolate (Lonhala Magnair) utilizes the eFlow technology system, developed by Pari Pharma. This nebulizing system is portable, virtually silent, and delivers the drug in 2-3 minutes, according to a statement from Sunovion Pharmaceuticals.

[email protected]

The Food and Drug Administration has given the nod to the first nebulized long-acting muscarinic antagonist (LAMA) treatment for chronic obstructive pulmonary disease (COPD) in the United States.

This product, glycopyrrolate, has specifically been approved for use as a long-term maintenance treatment of air-flow obstruction in patients with COPD. Glycopyrrolate (Lonhala Magnair) utilizes the eFlow technology system, developed by Pari Pharma. This nebulizing system is portable, virtually silent, and delivers the drug in 2-3 minutes, according to a statement from Sunovion Pharmaceuticals.

[email protected]

The Food and Drug Administration announced Dec. 12 the approval of mepolizumab (Nucala) to treat adult patients with eosinophilic granulomatosis with polyangiitis (EGPA), making it the first FDA-approved therapy intended to treat this rare disease.

Approval was based on data from a 52-week clinical trial that compared mepolizumab with placebo, according to the FDA. Patients received 300 mg of mepolizumab once every 4 weeks while continuing stable daily oral corticosteroid therapy. Those patients receiving mepolizumab “achieved a significantly greater accrued time in remission compared with placebo,” and a significantly higher proportion of patients receiving 300 mg of mepolizumab had achieved remission at week 36 and week 48, the statement said. Additionally, significantly more patients treated with mepolizumab achieved remission within the first 24 weeks and remained in remission for the remainder of the 52-week study treatment period.

[email protected]

SOURCE: FDA.gov

The Food and Drug Administration announced Dec. 12 the approval of mepolizumab (Nucala) to treat adult patients with eosinophilic granulomatosis with polyangiitis (EGPA), making it the first FDA-approved therapy intended to treat this rare disease.

Approval was based on data from a 52-week clinical trial that compared mepolizumab with placebo, according to the FDA. Patients received 300 mg of mepolizumab once every 4 weeks while continuing stable daily oral corticosteroid therapy. Those patients receiving mepolizumab “achieved a significantly greater accrued time in remission compared with placebo,” and a significantly higher proportion of patients receiving 300 mg of mepolizumab had achieved remission at week 36 and week 48, the statement said. Additionally, significantly more patients treated with mepolizumab achieved remission within the first 24 weeks and remained in remission for the remainder of the 52-week study treatment period.

[email protected]

SOURCE: FDA.gov

The Food and Drug Administration announced Dec. 12 the approval of mepolizumab (Nucala) to treat adult patients with eosinophilic granulomatosis with polyangiitis (EGPA), making it the first FDA-approved therapy intended to treat this rare disease.

Approval was based on data from a 52-week clinical trial that compared mepolizumab with placebo, according to the FDA. Patients received 300 mg of mepolizumab once every 4 weeks while continuing stable daily oral corticosteroid therapy. Those patients receiving mepolizumab “achieved a significantly greater accrued time in remission compared with placebo,” and a significantly higher proportion of patients receiving 300 mg of mepolizumab had achieved remission at week 36 and week 48, the statement said. Additionally, significantly more patients treated with mepolizumab achieved remission within the first 24 weeks and remained in remission for the remainder of the 52-week study treatment period.

[email protected]

SOURCE: FDA.gov

The National Institutes of Health has launched two large HIV clinical trials in Africa: one to investigate the efficacy of a long-acting injectable anti-HIV drug and one to test an experimental new HIV vaccine.

The first is a phase 3 trial comparing an injectable version of the investigational integrase inhibitor cabotegravir with pre-exposure prophylaxis (PrEP) using daily oral Truvada (emtricitabine). Researchers aim to recruit 3,200 sexually active women from across Southern and Eastern Africa, and follow them for an average of 2.6 years.

The National Institutes of Health has launched two large HIV clinical trials in Africa: one to investigate the efficacy of a long-acting injectable anti-HIV drug and one to test an experimental new HIV vaccine.

The first is a phase 3 trial comparing an injectable version of the investigational integrase inhibitor cabotegravir with pre-exposure prophylaxis (PrEP) using daily oral Truvada (emtricitabine). Researchers aim to recruit 3,200 sexually active women from across Southern and Eastern Africa, and follow them for an average of 2.6 years.

The National Institutes of Health has launched two large HIV clinical trials in Africa: one to investigate the efficacy of a long-acting injectable anti-HIV drug and one to test an experimental new HIV vaccine.

The first is a phase 3 trial comparing an injectable version of the investigational integrase inhibitor cabotegravir with pre-exposure prophylaxis (PrEP) using daily oral Truvada (emtricitabine). Researchers aim to recruit 3,200 sexually active women from across Southern and Eastern Africa, and follow them for an average of 2.6 years.

Recently I mentioned RSS news feeds as a useful, versatile online tool, but because it has been a while since I’ve discussed RSS feeds, an update is certainly in order.

The sheer volume of information on the web makes quick and efficient searching an indispensable skill, but once you have become quick and efficient at finding the information you need, a new problem arises: The information changes! All the good medical, news, and other information-based websites change and update their content on a regular, but unpredictable basis. And checking each one for new information can be very tedious, if you can remember to do it at all.

Many sites offer an e-mail service to notify you of new content, but multiple e-mail subscriptions clutter your inbox and often can’t select out the information you’re really interested in. RSS feeds are a more efficient and increasingly popular method of staying current on all the subjects that interest you – medical and otherwise. RSS (which stands for “Rich Site Summary” or “Really Simple Syndication,” depending on whom you ask) is a file format, and websites use that format (or a similar one called Atom) to produce a summary file, or “feed,” of new content, along with links to full versions of that content. When you subscribe to a given website’s feed, you’ll receive a summary of new content each time the website is updated.

Thousands of websites now offer RSS feeds, including most of the large medical information services, all the major news organizations, and many web logs.

FotoMaximum/Thinkstock

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected]

Recently I mentioned RSS news feeds as a useful, versatile online tool, but because it has been a while since I’ve discussed RSS feeds, an update is certainly in order.

The sheer volume of information on the web makes quick and efficient searching an indispensable skill, but once you have become quick and efficient at finding the information you need, a new problem arises: The information changes! All the good medical, news, and other information-based websites change and update their content on a regular, but unpredictable basis. And checking each one for new information can be very tedious, if you can remember to do it at all.

Many sites offer an e-mail service to notify you of new content, but multiple e-mail subscriptions clutter your inbox and often can’t select out the information you’re really interested in. RSS feeds are a more efficient and increasingly popular method of staying current on all the subjects that interest you – medical and otherwise. RSS (which stands for “Rich Site Summary” or “Really Simple Syndication,” depending on whom you ask) is a file format, and websites use that format (or a similar one called Atom) to produce a summary file, or “feed,” of new content, along with links to full versions of that content. When you subscribe to a given website’s feed, you’ll receive a summary of new content each time the website is updated.

Thousands of websites now offer RSS feeds, including most of the large medical information services, all the major news organizations, and many web logs.

FotoMaximum/Thinkstock

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected]

Recently I mentioned RSS news feeds as a useful, versatile online tool, but because it has been a while since I’ve discussed RSS feeds, an update is certainly in order.

The sheer volume of information on the web makes quick and efficient searching an indispensable skill, but once you have become quick and efficient at finding the information you need, a new problem arises: The information changes! All the good medical, news, and other information-based websites change and update their content on a regular, but unpredictable basis. And checking each one for new information can be very tedious, if you can remember to do it at all.

Many sites offer an e-mail service to notify you of new content, but multiple e-mail subscriptions clutter your inbox and often can’t select out the information you’re really interested in. RSS feeds are a more efficient and increasingly popular method of staying current on all the subjects that interest you – medical and otherwise. RSS (which stands for “Rich Site Summary” or “Really Simple Syndication,” depending on whom you ask) is a file format, and websites use that format (or a similar one called Atom) to produce a summary file, or “feed,” of new content, along with links to full versions of that content. When you subscribe to a given website’s feed, you’ll receive a summary of new content each time the website is updated.

Thousands of websites now offer RSS feeds, including most of the large medical information services, all the major news organizations, and many web logs.

FotoMaximum/Thinkstock

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected]

ATLANTA – The rate of venous thromboembolism (VTE) in patients with non-Hodgkin lymphoma (NHL) treated with lenalidomide is similar to that seen in multiple myeloma, according to results of recent systematic review and meta-analysis of trials representing more than 10,000 treatment cycles.

Although rates of VTE for NHL and myeloma could not be directly compared statistically, the finding may have clinical implications for NHL patients, said lead study author Samuel Yamshon, MD, an internal medicine resident at Cornell University, New York.

“Although outpatient VTE prophylaxis is not currently recommended, it should be carefully considered in patients with lymphoma being treated with lenalidomide, especially those receiving lenalidomide as a single agent,” Dr. Yamshon said in a presentation of the results at the annual meeting of the American Society of Hematology.

The rate of thrombosis in patients with B cell NHL who received lenalidomide treatment was 0.75 events per 100 patient-cycles, according to results of the meta-analysis, which was based on 28 articles including 10,332 cycles of lenalidomide received by patients with B-cell NHL.

Reported rates of thrombosis in previously untreated myeloma patients treated with lenalidomide are between 0.7 and 0.8 per 100 patient-cycles, Dr. Yamshon said in his presentation.

Notably, single-agent lenalidomide was linked with a significantly increased risk of thrombosis compared with lenalidomide treatment in combinations. The relative risk of VTE for lenalidomide as a single agent versus lenalidomide in combination was 2.01 (95% confidence interval, 1.28-3.16; P = .002), according to the presented data.

The investigators were unsure why single-agent lenalidomide appeared to have caused increased rates of thrombosis compared to lenalidomide in combinations. “Perhaps patients treated with additional agents have a lower tumor burden, leading to less venous obstruction causing clots, or perhaps there’s a direct interaction between lenalidomide and tumor leading to effects on the vasculature and mediators of coagulation,” Dr. Yamshon said.

Chemotherapy and biologic combinations had somewhat different VTE rates when compared to single-agent lenalidomide. The rate in patients receiving lenalidomide alone was 1.06 events per 100 patient-cycles, compared with 0.73 and 0.41 events per 100 patient-cycles, respectively, for lenalidomide plus chemotherapy and lenalidomide plus biologics.

However, the lower event rate with lenalidomide and biologics compared with lenalidomide and chemotherapy was a “nonsignificant trend” that was likely caused by differences in patient characteristics between the two cohorts, according to Dr. Yamshon.

None of the studies included in the meta-analysis were prospectively designed to measure VTE as a primary or secondary outcome, Dr. Yamshon noted in a discussion of the study’s limitations.

Further studies are warranted to determine lenalidomide’s effect on the vasculature and how it effects mediators of coagulation, he added.

Based on the current results, Dr. Yamshon said it may be reasonable to consider VTE prophylaxis in NHL patients receiving lenalidomide.

“If we’re going to be recommending outpatient VTE prophylaxis in everyone on lenalidomide in multiple myeloma, and the rates (of VTE) are the same, I think it certainly makes sense based on the data to recommend it,” he said in a question-and-answer session.

Dr. Yamshon reported no conflicts related to the study. Coauthors reported disclosures related to Roche, Celgene, Seattle Genetics, Pharmacyclics, Cell Medica, Janssen, and AstraZeneca.

SOURCE: Yamshon S et al. Abstract 677.

ATLANTA – The rate of venous thromboembolism (VTE) in patients with non-Hodgkin lymphoma (NHL) treated with lenalidomide is similar to that seen in multiple myeloma, according to results of recent systematic review and meta-analysis of trials representing more than 10,000 treatment cycles.

Although rates of VTE for NHL and myeloma could not be directly compared statistically, the finding may have clinical implications for NHL patients, said lead study author Samuel Yamshon, MD, an internal medicine resident at Cornell University, New York.

“Although outpatient VTE prophylaxis is not currently recommended, it should be carefully considered in patients with lymphoma being treated with lenalidomide, especially those receiving lenalidomide as a single agent,” Dr. Yamshon said in a presentation of the results at the annual meeting of the American Society of Hematology.

The rate of thrombosis in patients with B cell NHL who received lenalidomide treatment was 0.75 events per 100 patient-cycles, according to results of the meta-analysis, which was based on 28 articles including 10,332 cycles of lenalidomide received by patients with B-cell NHL.

Reported rates of thrombosis in previously untreated myeloma patients treated with lenalidomide are between 0.7 and 0.8 per 100 patient-cycles, Dr. Yamshon said in his presentation.

Notably, single-agent lenalidomide was linked with a significantly increased risk of thrombosis compared with lenalidomide treatment in combinations. The relative risk of VTE for lenalidomide as a single agent versus lenalidomide in combination was 2.01 (95% confidence interval, 1.28-3.16; P = .002), according to the presented data.

The investigators were unsure why single-agent lenalidomide appeared to have caused increased rates of thrombosis compared to lenalidomide in combinations. “Perhaps patients treated with additional agents have a lower tumor burden, leading to less venous obstruction causing clots, or perhaps there’s a direct interaction between lenalidomide and tumor leading to effects on the vasculature and mediators of coagulation,” Dr. Yamshon said.

Chemotherapy and biologic combinations had somewhat different VTE rates when compared to single-agent lenalidomide. The rate in patients receiving lenalidomide alone was 1.06 events per 100 patient-cycles, compared with 0.73 and 0.41 events per 100 patient-cycles, respectively, for lenalidomide plus chemotherapy and lenalidomide plus biologics.

However, the lower event rate with lenalidomide and biologics compared with lenalidomide and chemotherapy was a “nonsignificant trend” that was likely caused by differences in patient characteristics between the two cohorts, according to Dr. Yamshon.

None of the studies included in the meta-analysis were prospectively designed to measure VTE as a primary or secondary outcome, Dr. Yamshon noted in a discussion of the study’s limitations.

Further studies are warranted to determine lenalidomide’s effect on the vasculature and how it effects mediators of coagulation, he added.

Based on the current results, Dr. Yamshon said it may be reasonable to consider VTE prophylaxis in NHL patients receiving lenalidomide.

“If we’re going to be recommending outpatient VTE prophylaxis in everyone on lenalidomide in multiple myeloma, and the rates (of VTE) are the same, I think it certainly makes sense based on the data to recommend it,” he said in a question-and-answer session.

Dr. Yamshon reported no conflicts related to the study. Coauthors reported disclosures related to Roche, Celgene, Seattle Genetics, Pharmacyclics, Cell Medica, Janssen, and AstraZeneca.

SOURCE: Yamshon S et al. Abstract 677.

ATLANTA – The rate of venous thromboembolism (VTE) in patients with non-Hodgkin lymphoma (NHL) treated with lenalidomide is similar to that seen in multiple myeloma, according to results of recent systematic review and meta-analysis of trials representing more than 10,000 treatment cycles.

Although rates of VTE for NHL and myeloma could not be directly compared statistically, the finding may have clinical implications for NHL patients, said lead study author Samuel Yamshon, MD, an internal medicine resident at Cornell University, New York.

“Although outpatient VTE prophylaxis is not currently recommended, it should be carefully considered in patients with lymphoma being treated with lenalidomide, especially those receiving lenalidomide as a single agent,” Dr. Yamshon said in a presentation of the results at the annual meeting of the American Society of Hematology.

The rate of thrombosis in patients with B cell NHL who received lenalidomide treatment was 0.75 events per 100 patient-cycles, according to results of the meta-analysis, which was based on 28 articles including 10,332 cycles of lenalidomide received by patients with B-cell NHL.

Reported rates of thrombosis in previously untreated myeloma patients treated with lenalidomide are between 0.7 and 0.8 per 100 patient-cycles, Dr. Yamshon said in his presentation.

Notably, single-agent lenalidomide was linked with a significantly increased risk of thrombosis compared with lenalidomide treatment in combinations. The relative risk of VTE for lenalidomide as a single agent versus lenalidomide in combination was 2.01 (95% confidence interval, 1.28-3.16; P = .002), according to the presented data.

The investigators were unsure why single-agent lenalidomide appeared to have caused increased rates of thrombosis compared to lenalidomide in combinations. “Perhaps patients treated with additional agents have a lower tumor burden, leading to less venous obstruction causing clots, or perhaps there’s a direct interaction between lenalidomide and tumor leading to effects on the vasculature and mediators of coagulation,” Dr. Yamshon said.

Chemotherapy and biologic combinations had somewhat different VTE rates when compared to single-agent lenalidomide. The rate in patients receiving lenalidomide alone was 1.06 events per 100 patient-cycles, compared with 0.73 and 0.41 events per 100 patient-cycles, respectively, for lenalidomide plus chemotherapy and lenalidomide plus biologics.

However, the lower event rate with lenalidomide and biologics compared with lenalidomide and chemotherapy was a “nonsignificant trend” that was likely caused by differences in patient characteristics between the two cohorts, according to Dr. Yamshon.

None of the studies included in the meta-analysis were prospectively designed to measure VTE as a primary or secondary outcome, Dr. Yamshon noted in a discussion of the study’s limitations.

Further studies are warranted to determine lenalidomide’s effect on the vasculature and how it effects mediators of coagulation, he added.

Based on the current results, Dr. Yamshon said it may be reasonable to consider VTE prophylaxis in NHL patients receiving lenalidomide.

“If we’re going to be recommending outpatient VTE prophylaxis in everyone on lenalidomide in multiple myeloma, and the rates (of VTE) are the same, I think it certainly makes sense based on the data to recommend it,” he said in a question-and-answer session.

Dr. Yamshon reported no conflicts related to the study. Coauthors reported disclosures related to Roche, Celgene, Seattle Genetics, Pharmacyclics, Cell Medica, Janssen, and AstraZeneca.

SOURCE: Yamshon S et al. Abstract 677.

SAN ANTONIO – Treatment with cyclin-dependent kinase 4/6 inhibitors (CDK4/6) appears to have the same efficacy in older breast cancer patients, as compared to younger ones, according to new findings presented at the San Antonio Breast Cancer Symposium.

Women aged 65 years and older with hormone receptor (HR)–positive, HER2-negative metastatic breast cancer who received CDK4/6 inhibitors achieved a rate of progression-free survival (PFS) similar to that which has been reported in younger patients. Importantly, combining a CDK4/6 inhibitor with endocrine therapy led to superior PFS as compared to endocrine therapy alone.

However, older patients appeared to be less tolerant of associated adverse events and were more likely to discontinue treatment for that reason.

“Older patients with breast cancer benefit from treatment with CDK4/6 inhibitors ... for HR-positive, HER2-negative, metastatic breast cancer,” said the study’s lead author, Harpreet Singh, MD, scientific liaison for the FDA’s Cancer in Older Adults and a medical officer in the Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, at the Food and Drug Administration.

“The severity of adverse events and rates of dose modifications and interruptions were higher in those 65 years of age and older and those 70 years and older,” Dr. Singh said. “Rates of selected adverse events were similar across pooled trials.”

Breast cancer is a disease of aging, and 72,000 breast cancers occur annually in women aged 70 years or older, she explained. “Most cancers in older women are lower risk tumors and most older patients will die of other causes, but approximately 40% of breast cancer related deaths are in women over the age of 70.

“But the accrual of older individuals in trials has been a persistent challenge,” said Dr. Singh. “Older patients traditionally have been underrepresented in oncology clinical trials, so pooling outcomes of older patients across clinical trials in the same drug class allows us to gain insight into how these patients may benefit.”

In the current study, which was an FDA-conducted review of FDA registration trials over a 10 year period, the authors found that fewer than 60% of new cases of breast cancer are diagnosed in women under the age of 65 years.

“But these women make up about 80% of the clinical trial populations even though they are only 57% of cases,” said Dr. Singh.

Only 17% of clinical trial populations comprised individuals aged 65-74 years – even though patients aged 75 years and older make up about 20% of new cases, they comprise only 4% of the clinical trial population.

The FDA has issued several guidances that encourage investigators to enroll older women into trials but does not require them to. Only 22% of patients over 70 received adjuvant or neoadjuvant therapy compared to close to 50% of younger patients, and as a result, very little is known about the safety and efficacy of these agents in older adults.

To assess the efficacy and safety of CDK4/6 inhibitors in an older population, Dr. Singh and her colleagues pooled and analyzed data from prospective, randomized, controlled trials that evaluated three different CDK4/6 inhibitors in combination with an aromatase inhibitor, as the first-line treatment for postmenopausal patients with HR-positive metastatic breast cancer. The cohort included 1,334 patients, (intention-to-treat population, 1,992), of whom 42% were aged 65 years or older, and 24% were 70 years or older.

The primary endpoint was PFS in patients aged 70 years and older, and in control groups.

For patients 70 years or older who received a CDK4/6 inhibitor in combination with an aromatase inhibitor, the estimated PFS was not reached (25.1 months, not reached), versus 16.8 months (13.7, 21.9) for those who received an aromatase inhibitor only.

For patients younger than 70 years of age, PFS also was superior among those who received a CDK4/6 inhibitor, compared with treatment with an aromatase inhibitor alone: 23.75(21.9, 25.4) months versus an estimated 13.8 months (12.9, 14.7).

There were no treatment differences across age subgroups and similar results with alternate age cut-offs (greater than 65 years, greater than 75 years, etc.).

When looking at safety, the authors found that older patients were more likely to stop treatment because of adverse events. Among those 70 years and older, 20% discontinued treatment as compared with 17% of those 65 years or older, and 8% of those under the age of 65 years. Virtually all patients in the three age groups experienced grade 1-2 events (younger than 65, 98%; greater than or equal to 65 years, 98%; greater than or equal to 70 years, 99%), and the majority experienced grade 3-4 events (76%, 83%, 85%, respectively), with the rate higher in the older age groups. More than three quarters of all patients experienced neutropenia (76%, 77%, 80%), and two-thirds or higher grade 3-4 neutropenia (65%, 69%, 72%). Adverse events leading to dose interruption and/or reduction were also higher in the older age groups (66%, 75%, 77%).

“But there are many signs of progress,” said Dr. Singh, referring to efforts in enrolling more older breast cancer patients in clinical trials. “There are ongoing efforts to modernize eligibility criteria which will include greater inclusion of older adults, and specifically, taking a rational approach to organ dysfunction and prior malignancies.”

The increased use of patient-reported outcomes will provide further information on the tolerability of therapy. “Also the acquisition of real-world data from more diverse oncology practices will help inform data on efficacy and safety of novel therapies in older adults,” concluded Dr. Singh.

SOURCE: Singh et al., SABCS 2017 Abstract GS5-06.

SAN ANTONIO – Treatment with cyclin-dependent kinase 4/6 inhibitors (CDK4/6) appears to have the same efficacy in older breast cancer patients, as compared to younger ones, according to new findings presented at the San Antonio Breast Cancer Symposium.

Women aged 65 years and older with hormone receptor (HR)–positive, HER2-negative metastatic breast cancer who received CDK4/6 inhibitors achieved a rate of progression-free survival (PFS) similar to that which has been reported in younger patients. Importantly, combining a CDK4/6 inhibitor with endocrine therapy led to superior PFS as compared to endocrine therapy alone.

However, older patients appeared to be less tolerant of associated adverse events and were more likely to discontinue treatment for that reason.

“Older patients with breast cancer benefit from treatment with CDK4/6 inhibitors ... for HR-positive, HER2-negative, metastatic breast cancer,” said the study’s lead author, Harpreet Singh, MD, scientific liaison for the FDA’s Cancer in Older Adults and a medical officer in the Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, at the Food and Drug Administration.

“The severity of adverse events and rates of dose modifications and interruptions were higher in those 65 years of age and older and those 70 years and older,” Dr. Singh said. “Rates of selected adverse events were similar across pooled trials.”

Breast cancer is a disease of aging, and 72,000 breast cancers occur annually in women aged 70 years or older, she explained. “Most cancers in older women are lower risk tumors and most older patients will die of other causes, but approximately 40% of breast cancer related deaths are in women over the age of 70.

“But the accrual of older individuals in trials has been a persistent challenge,” said Dr. Singh. “Older patients traditionally have been underrepresented in oncology clinical trials, so pooling outcomes of older patients across clinical trials in the same drug class allows us to gain insight into how these patients may benefit.”

In the current study, which was an FDA-conducted review of FDA registration trials over a 10 year period, the authors found that fewer than 60% of new cases of breast cancer are diagnosed in women under the age of 65 years.

“But these women make up about 80% of the clinical trial populations even though they are only 57% of cases,” said Dr. Singh.

Only 17% of clinical trial populations comprised individuals aged 65-74 years – even though patients aged 75 years and older make up about 20% of new cases, they comprise only 4% of the clinical trial population.

The FDA has issued several guidances that encourage investigators to enroll older women into trials but does not require them to. Only 22% of patients over 70 received adjuvant or neoadjuvant therapy compared to close to 50% of younger patients, and as a result, very little is known about the safety and efficacy of these agents in older adults.

To assess the efficacy and safety of CDK4/6 inhibitors in an older population, Dr. Singh and her colleagues pooled and analyzed data from prospective, randomized, controlled trials that evaluated three different CDK4/6 inhibitors in combination with an aromatase inhibitor, as the first-line treatment for postmenopausal patients with HR-positive metastatic breast cancer. The cohort included 1,334 patients, (intention-to-treat population, 1,992), of whom 42% were aged 65 years or older, and 24% were 70 years or older.

The primary endpoint was PFS in patients aged 70 years and older, and in control groups.

For patients 70 years or older who received a CDK4/6 inhibitor in combination with an aromatase inhibitor, the estimated PFS was not reached (25.1 months, not reached), versus 16.8 months (13.7, 21.9) for those who received an aromatase inhibitor only.

For patients younger than 70 years of age, PFS also was superior among those who received a CDK4/6 inhibitor, compared with treatment with an aromatase inhibitor alone: 23.75(21.9, 25.4) months versus an estimated 13.8 months (12.9, 14.7).

There were no treatment differences across age subgroups and similar results with alternate age cut-offs (greater than 65 years, greater than 75 years, etc.).

When looking at safety, the authors found that older patients were more likely to stop treatment because of adverse events. Among those 70 years and older, 20% discontinued treatment as compared with 17% of those 65 years or older, and 8% of those under the age of 65 years. Virtually all patients in the three age groups experienced grade 1-2 events (younger than 65, 98%; greater than or equal to 65 years, 98%; greater than or equal to 70 years, 99%), and the majority experienced grade 3-4 events (76%, 83%, 85%, respectively), with the rate higher in the older age groups. More than three quarters of all patients experienced neutropenia (76%, 77%, 80%), and two-thirds or higher grade 3-4 neutropenia (65%, 69%, 72%). Adverse events leading to dose interruption and/or reduction were also higher in the older age groups (66%, 75%, 77%).

“But there are many signs of progress,” said Dr. Singh, referring to efforts in enrolling more older breast cancer patients in clinical trials. “There are ongoing efforts to modernize eligibility criteria which will include greater inclusion of older adults, and specifically, taking a rational approach to organ dysfunction and prior malignancies.”

The increased use of patient-reported outcomes will provide further information on the tolerability of therapy. “Also the acquisition of real-world data from more diverse oncology practices will help inform data on efficacy and safety of novel therapies in older adults,” concluded Dr. Singh.

SOURCE: Singh et al., SABCS 2017 Abstract GS5-06.

SAN ANTONIO – Treatment with cyclin-dependent kinase 4/6 inhibitors (CDK4/6) appears to have the same efficacy in older breast cancer patients, as compared to younger ones, according to new findings presented at the San Antonio Breast Cancer Symposium.

Women aged 65 years and older with hormone receptor (HR)–positive, HER2-negative metastatic breast cancer who received CDK4/6 inhibitors achieved a rate of progression-free survival (PFS) similar to that which has been reported in younger patients. Importantly, combining a CDK4/6 inhibitor with endocrine therapy led to superior PFS as compared to endocrine therapy alone.

However, older patients appeared to be less tolerant of associated adverse events and were more likely to discontinue treatment for that reason.

“Older patients with breast cancer benefit from treatment with CDK4/6 inhibitors ... for HR-positive, HER2-negative, metastatic breast cancer,” said the study’s lead author, Harpreet Singh, MD, scientific liaison for the FDA’s Cancer in Older Adults and a medical officer in the Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, at the Food and Drug Administration.

“The severity of adverse events and rates of dose modifications and interruptions were higher in those 65 years of age and older and those 70 years and older,” Dr. Singh said. “Rates of selected adverse events were similar across pooled trials.”

Breast cancer is a disease of aging, and 72,000 breast cancers occur annually in women aged 70 years or older, she explained. “Most cancers in older women are lower risk tumors and most older patients will die of other causes, but approximately 40% of breast cancer related deaths are in women over the age of 70.

“But the accrual of older individuals in trials has been a persistent challenge,” said Dr. Singh. “Older patients traditionally have been underrepresented in oncology clinical trials, so pooling outcomes of older patients across clinical trials in the same drug class allows us to gain insight into how these patients may benefit.”

In the current study, which was an FDA-conducted review of FDA registration trials over a 10 year period, the authors found that fewer than 60% of new cases of breast cancer are diagnosed in women under the age of 65 years.

“But these women make up about 80% of the clinical trial populations even though they are only 57% of cases,” said Dr. Singh.

Only 17% of clinical trial populations comprised individuals aged 65-74 years – even though patients aged 75 years and older make up about 20% of new cases, they comprise only 4% of the clinical trial population.

The FDA has issued several guidances that encourage investigators to enroll older women into trials but does not require them to. Only 22% of patients over 70 received adjuvant or neoadjuvant therapy compared to close to 50% of younger patients, and as a result, very little is known about the safety and efficacy of these agents in older adults.

To assess the efficacy and safety of CDK4/6 inhibitors in an older population, Dr. Singh and her colleagues pooled and analyzed data from prospective, randomized, controlled trials that evaluated three different CDK4/6 inhibitors in combination with an aromatase inhibitor, as the first-line treatment for postmenopausal patients with HR-positive metastatic breast cancer. The cohort included 1,334 patients, (intention-to-treat population, 1,992), of whom 42% were aged 65 years or older, and 24% were 70 years or older.

The primary endpoint was PFS in patients aged 70 years and older, and in control groups.

For patients 70 years or older who received a CDK4/6 inhibitor in combination with an aromatase inhibitor, the estimated PFS was not reached (25.1 months, not reached), versus 16.8 months (13.7, 21.9) for those who received an aromatase inhibitor only.

For patients younger than 70 years of age, PFS also was superior among those who received a CDK4/6 inhibitor, compared with treatment with an aromatase inhibitor alone: 23.75(21.9, 25.4) months versus an estimated 13.8 months (12.9, 14.7).

There were no treatment differences across age subgroups and similar results with alternate age cut-offs (greater than 65 years, greater than 75 years, etc.).

When looking at safety, the authors found that older patients were more likely to stop treatment because of adverse events. Among those 70 years and older, 20% discontinued treatment as compared with 17% of those 65 years or older, and 8% of those under the age of 65 years. Virtually all patients in the three age groups experienced grade 1-2 events (younger than 65, 98%; greater than or equal to 65 years, 98%; greater than or equal to 70 years, 99%), and the majority experienced grade 3-4 events (76%, 83%, 85%, respectively), with the rate higher in the older age groups. More than three quarters of all patients experienced neutropenia (76%, 77%, 80%), and two-thirds or higher grade 3-4 neutropenia (65%, 69%, 72%). Adverse events leading to dose interruption and/or reduction were also higher in the older age groups (66%, 75%, 77%).

“But there are many signs of progress,” said Dr. Singh, referring to efforts in enrolling more older breast cancer patients in clinical trials. “There are ongoing efforts to modernize eligibility criteria which will include greater inclusion of older adults, and specifically, taking a rational approach to organ dysfunction and prior malignancies.”

The increased use of patient-reported outcomes will provide further information on the tolerability of therapy. “Also the acquisition of real-world data from more diverse oncology practices will help inform data on efficacy and safety of novel therapies in older adults,” concluded Dr. Singh.

SOURCE: Singh et al., SABCS 2017 Abstract GS5-06.

ATLANTA – Twelve months of daily treatment with the novel oral factor Xa inhibitor edoxaban was noninferior to standard subcutaneous therapy with dalteparin for treatment of venous thromboembolism in patients with cancer, according to late-breaking results from a randomized, open-label, blinded-outcomes trial.

Throughout follow-up, trial arms had nearly identical rates of survival free from recurrent VTE or major bleeding, Gary E. Raskob, PhD, reported during a late-breaking oral presentation at the annual meeting of the American Society of Hematology. “Edoxaban was associated with a lower rate of recurrent VTE, which was offset by a similar increase in risk of major bleeding,” he said. “Therefore, oral edoxaban was noninferior to subcutaneous dalteparin for the [combined] primary outcome.”

Venous thromboembolism affects about one in five patients with active cancer and is difficult to treat because patients face increased risks of recurrence and bleeding. The struggle to balance these risks fuels morbidity and mortality and can hamper cancer treatment, said Dr. Raskob of the University of Oklahoma, Oklahoma City.

Pharmacy and medical oncology societies recommend long-term low-molecular-weight heparin for cancer patients with VTE, but the daily burden of subcutaneous injections leads many to stop after about 2-4 months of treatment, Dr. Raskob said. “Direct oral anticoagulants may be an attractive alternative.”

For the trial, 1,446 adults with cancer and lower limb VTE from 114 clinics in North America, Europe, Australia, and New Zealand received either edoxaban (60 mg daily) or dalteparin (200 IU/kg for 30 days, followed by 150 IU/kg) for up to 12 months. Nearly all patients had active cancer. Tumor types reflected what’s most common in practice, such as malignancies of the lung, colon, and breast. About 50 patients had primary or metastatic brain cancers. Approximately two-thirds had pulmonary embolism with or without deep-vein thrombosis, while the rest had isolated deep-vein thrombosis.

After 12 months of follow-up, 12.8% of edoxaban patients had at least one recurrence of VTE or a major bleed, compared with 13.5% of dalteparin patients (hazard ratio, 0.97; 95% confidence interval, 0.70-1.36; P = .006 for noninferiority). Edoxaban also was noninferior to dalteparin after the first 6 months of treatment and in the per-protocol analysis (HRs, 1.0; P = .02 for noninferiority in each analysis). Thus, differences in efficacy did not only reflect better compliance to oral therapy, Dr. Raskob said.

He also reported on individual outcomes. In all, 10.3% of dalteparin recipients had a VTE recurrence, as did 6.5% of edoxaban recipients, for a risk difference of 3.8% (95% CI, 7.1%-0.4%). More than half of recurrences in each group were symptomatic, and none were fatal. Bleeding caused no deaths in either study arm, and each therapy conferred an identical chance of a grade 3-4 major bleed (2.3%).

Edoxaban was associated, however, with a greater frequency of major bleeds (33 events; 6.3%) than was dalteparin (17 events; 3.2%; risk difference, 3.1%; 95% CI, 0.5%-5.7%). In particular, patients who received edoxaban had a slightly higher rate of upper gastrointestinal bleeds. Most had gastric cancer.

Future studies should evaluate whether these patients should receive a lower dose of edoxaban, said Dr. Raskob. “We don’t yet fully know the minimum effective dose [of edoxaban] in cancer patients.”

He also addressed the idea that heparin has antineoplastic activity, calling it “one we should probably abandon. The concept originates from older trials in which researchers probably did not recognize that heparin was preventing fatal pulmonary embolism, he said.

The investigators soon will begin deeper analyses that should inform patient selection, he said. For now, he recommends discussing these findings with patients to help them make an informed choice between oral anticoagulation, with its ease of use but slightly higher rate of major bleeds, and subcutaneous heparin, with its lower bleeding rate and treatment burden.

Daiichi Sankyo provided funding. Dr. Raskob disclosed consulting relationships and honoraria from Daiichi Sankyo, Eli Lilly, Janssen, and several other pharmaceutical companies.

SOURCE: Raskob G et al. ASH Abstract LBA-6.

ATLANTA – Twelve months of daily treatment with the novel oral factor Xa inhibitor edoxaban was noninferior to standard subcutaneous therapy with dalteparin for treatment of venous thromboembolism in patients with cancer, according to late-breaking results from a randomized, open-label, blinded-outcomes trial.

Throughout follow-up, trial arms had nearly identical rates of survival free from recurrent VTE or major bleeding, Gary E. Raskob, PhD, reported during a late-breaking oral presentation at the annual meeting of the American Society of Hematology. “Edoxaban was associated with a lower rate of recurrent VTE, which was offset by a similar increase in risk of major bleeding,” he said. “Therefore, oral edoxaban was noninferior to subcutaneous dalteparin for the [combined] primary outcome.”

Venous thromboembolism affects about one in five patients with active cancer and is difficult to treat because patients face increased risks of recurrence and bleeding. The struggle to balance these risks fuels morbidity and mortality and can hamper cancer treatment, said Dr. Raskob of the University of Oklahoma, Oklahoma City.

Pharmacy and medical oncology societies recommend long-term low-molecular-weight heparin for cancer patients with VTE, but the daily burden of subcutaneous injections leads many to stop after about 2-4 months of treatment, Dr. Raskob said. “Direct oral anticoagulants may be an attractive alternative.”

For the trial, 1,446 adults with cancer and lower limb VTE from 114 clinics in North America, Europe, Australia, and New Zealand received either edoxaban (60 mg daily) or dalteparin (200 IU/kg for 30 days, followed by 150 IU/kg) for up to 12 months. Nearly all patients had active cancer. Tumor types reflected what’s most common in practice, such as malignancies of the lung, colon, and breast. About 50 patients had primary or metastatic brain cancers. Approximately two-thirds had pulmonary embolism with or without deep-vein thrombosis, while the rest had isolated deep-vein thrombosis.

After 12 months of follow-up, 12.8% of edoxaban patients had at least one recurrence of VTE or a major bleed, compared with 13.5% of dalteparin patients (hazard ratio, 0.97; 95% confidence interval, 0.70-1.36; P = .006 for noninferiority). Edoxaban also was noninferior to dalteparin after the first 6 months of treatment and in the per-protocol analysis (HRs, 1.0; P = .02 for noninferiority in each analysis). Thus, differences in efficacy did not only reflect better compliance to oral therapy, Dr. Raskob said.

He also reported on individual outcomes. In all, 10.3% of dalteparin recipients had a VTE recurrence, as did 6.5% of edoxaban recipients, for a risk difference of 3.8% (95% CI, 7.1%-0.4%). More than half of recurrences in each group were symptomatic, and none were fatal. Bleeding caused no deaths in either study arm, and each therapy conferred an identical chance of a grade 3-4 major bleed (2.3%).

Edoxaban was associated, however, with a greater frequency of major bleeds (33 events; 6.3%) than was dalteparin (17 events; 3.2%; risk difference, 3.1%; 95% CI, 0.5%-5.7%). In particular, patients who received edoxaban had a slightly higher rate of upper gastrointestinal bleeds. Most had gastric cancer.

Future studies should evaluate whether these patients should receive a lower dose of edoxaban, said Dr. Raskob. “We don’t yet fully know the minimum effective dose [of edoxaban] in cancer patients.”

He also addressed the idea that heparin has antineoplastic activity, calling it “one we should probably abandon. The concept originates from older trials in which researchers probably did not recognize that heparin was preventing fatal pulmonary embolism, he said.

The investigators soon will begin deeper analyses that should inform patient selection, he said. For now, he recommends discussing these findings with patients to help them make an informed choice between oral anticoagulation, with its ease of use but slightly higher rate of major bleeds, and subcutaneous heparin, with its lower bleeding rate and treatment burden.

Daiichi Sankyo provided funding. Dr. Raskob disclosed consulting relationships and honoraria from Daiichi Sankyo, Eli Lilly, Janssen, and several other pharmaceutical companies.

SOURCE: Raskob G et al. ASH Abstract LBA-6.

ATLANTA – Twelve months of daily treatment with the novel oral factor Xa inhibitor edoxaban was noninferior to standard subcutaneous therapy with dalteparin for treatment of venous thromboembolism in patients with cancer, according to late-breaking results from a randomized, open-label, blinded-outcomes trial.

Throughout follow-up, trial arms had nearly identical rates of survival free from recurrent VTE or major bleeding, Gary E. Raskob, PhD, reported during a late-breaking oral presentation at the annual meeting of the American Society of Hematology. “Edoxaban was associated with a lower rate of recurrent VTE, which was offset by a similar increase in risk of major bleeding,” he said. “Therefore, oral edoxaban was noninferior to subcutaneous dalteparin for the [combined] primary outcome.”

Venous thromboembolism affects about one in five patients with active cancer and is difficult to treat because patients face increased risks of recurrence and bleeding. The struggle to balance these risks fuels morbidity and mortality and can hamper cancer treatment, said Dr. Raskob of the University of Oklahoma, Oklahoma City.

Pharmacy and medical oncology societies recommend long-term low-molecular-weight heparin for cancer patients with VTE, but the daily burden of subcutaneous injections leads many to stop after about 2-4 months of treatment, Dr. Raskob said. “Direct oral anticoagulants may be an attractive alternative.”

For the trial, 1,446 adults with cancer and lower limb VTE from 114 clinics in North America, Europe, Australia, and New Zealand received either edoxaban (60 mg daily) or dalteparin (200 IU/kg for 30 days, followed by 150 IU/kg) for up to 12 months. Nearly all patients had active cancer. Tumor types reflected what’s most common in practice, such as malignancies of the lung, colon, and breast. About 50 patients had primary or metastatic brain cancers. Approximately two-thirds had pulmonary embolism with or without deep-vein thrombosis, while the rest had isolated deep-vein thrombosis.

After 12 months of follow-up, 12.8% of edoxaban patients had at least one recurrence of VTE or a major bleed, compared with 13.5% of dalteparin patients (hazard ratio, 0.97; 95% confidence interval, 0.70-1.36; P = .006 for noninferiority). Edoxaban also was noninferior to dalteparin after the first 6 months of treatment and in the per-protocol analysis (HRs, 1.0; P = .02 for noninferiority in each analysis). Thus, differences in efficacy did not only reflect better compliance to oral therapy, Dr. Raskob said.

He also reported on individual outcomes. In all, 10.3% of dalteparin recipients had a VTE recurrence, as did 6.5% of edoxaban recipients, for a risk difference of 3.8% (95% CI, 7.1%-0.4%). More than half of recurrences in each group were symptomatic, and none were fatal. Bleeding caused no deaths in either study arm, and each therapy conferred an identical chance of a grade 3-4 major bleed (2.3%).

Edoxaban was associated, however, with a greater frequency of major bleeds (33 events; 6.3%) than was dalteparin (17 events; 3.2%; risk difference, 3.1%; 95% CI, 0.5%-5.7%). In particular, patients who received edoxaban had a slightly higher rate of upper gastrointestinal bleeds. Most had gastric cancer.

Future studies should evaluate whether these patients should receive a lower dose of edoxaban, said Dr. Raskob. “We don’t yet fully know the minimum effective dose [of edoxaban] in cancer patients.”

He also addressed the idea that heparin has antineoplastic activity, calling it “one we should probably abandon. The concept originates from older trials in which researchers probably did not recognize that heparin was preventing fatal pulmonary embolism, he said.

The investigators soon will begin deeper analyses that should inform patient selection, he said. For now, he recommends discussing these findings with patients to help them make an informed choice between oral anticoagulation, with its ease of use but slightly higher rate of major bleeds, and subcutaneous heparin, with its lower bleeding rate and treatment burden.

Daiichi Sankyo provided funding. Dr. Raskob disclosed consulting relationships and honoraria from Daiichi Sankyo, Eli Lilly, Janssen, and several other pharmaceutical companies.

SOURCE: Raskob G et al. ASH Abstract LBA-6.

BERLIN – Teens who reported psychotic symptoms – especially hallucinations – on a baseline mental health screening were twice as likely to develop persistent psychiatric symptoms over the next year as were those without such experiences.

Hallucinations in particular predicted a persistent course, nearly tripling the risk (odds ratio, 2.74), Saliha El-Bouhaddani said at the meeting of the World Psychiatric Association.

“This is quite informative and quite clinically relevant,” said Ms. El-Bouhaddani, a doctoral student in psychology at the Parnassia Group, Rotterdam, the Netherlands. Because mental health symptoms in young people may be self-limiting, it’s not easy to identify which teens are at high risk for developing persistent problems that can predispose them to a full-blown mental disorder. “But we can see here that psychotic experiences may be very useful in detecting which adolescents may have persistency of symptoms. I believe that screening tools for teenagers should involve questions about psychotic symptoms, because the answer may help us discriminate who will have a self-limiting course and who will have a persistent course.”

Ms. El-Bouhaddani described MasterMind, a longitudinal cohort study of adolescents drawn from the general population. Each teen completed self-report questionnaires on psychotic experiences and psychosocial problems at two time points over a 2-year period. The study was divided into two phases: a 1-year observational period, followed by an intervention for those at risk, and then a 1-year treatment and follow-up period. She reported only the results of the observational phase.

The study enrolled 1,827 young people, who completed four questionnaires: the Strengths & Difficulties Questionnaire, and questionnaires about psychotic experiences, trauma, and self-esteem. One year later, 1,521 of the participants returned and completed the same surveys.

Ms. El-Bouhaddani constructed four potential pathways from baseline to follow-up: no psychiatric symptoms, remitting symptoms (baseline psychosocial symptoms that remitted by 1 year), incident symptoms (symptoms that appeared only at 1 year), and persistent symptoms (symptoms at both baseline and 1 year). Her goal was to identify any baseline characteristics that might predict a persistent course.

At the 1-year point, the cohort was a mean of 13.5 years old. Most subjects (1,134) had no symptoms at either time point. Incident symptoms were present in 151, remitting symptoms in 181, and persistent symptoms in 46.

Several baseline characteristics significantly separated the group with remitting symptoms from all other groups: They were significantly more likely to have a low education level (61%), to have divorced parents (38%), to report frequent household moves (22%), to have repeated a grade (31%), to report low self-esteem (15%), and to have somatic symptoms (3%). Teens with persistent symptoms also reported more somatic symptoms (3%), but they were significantly more likely than any of the other groups to report having had at least one traumatic event (45%).

At follow-up, psychotic incidents were significantly more common in the remitting and persistent groups (40% and 62%, respectively) than in the nonsymptomatic and incident groups (10% and 11%).

Ms. El-Bouhaddani then broke psychotic experiences down into hallucinations and delusions, and examined their relationships to symptom course. Hallucinations were significantly more common than delusions among those with a persistent course (58% vs. 42%).

She conducted a logistic regression analysis, which determined that any psychotic experience nearly doubled the risk of a persistent course of psychiatric symptoms (OR, 1.92). Hallucinations nearly tripled the risk (OR, 2.74), as did traumatic experiences (OR, 3.0). Delusions increased the risk by close to 60% (OR, 1.59).

The SDQ does not contain questions about psychotic experiences or trauma – the two most powerful predictors of persistent symptoms. It’s time to change this, Ms. El-Bouhaddani said.

“From these results it seems as though we should be asking adolescents about psychotic experiences and trauma. Perhaps it’s time for a new version of the SDQ.”

She had no relevant financial disclosures.

[email protected]

On Twitter @alz_gal

SOURCE: El-Bouhaddani S et al. WPA 2017 Abstract S-023 002.

BERLIN – Teens who reported psychotic symptoms – especially hallucinations – on a baseline mental health screening were twice as likely to develop persistent psychiatric symptoms over the next year as were those without such experiences.

Hallucinations in particular predicted a persistent course, nearly tripling the risk (odds ratio, 2.74), Saliha El-Bouhaddani said at the meeting of the World Psychiatric Association.

“This is quite informative and quite clinically relevant,” said Ms. El-Bouhaddani, a doctoral student in psychology at the Parnassia Group, Rotterdam, the Netherlands. Because mental health symptoms in young people may be self-limiting, it’s not easy to identify which teens are at high risk for developing persistent problems that can predispose them to a full-blown mental disorder. “But we can see here that psychotic experiences may be very useful in detecting which adolescents may have persistency of symptoms. I believe that screening tools for teenagers should involve questions about psychotic symptoms, because the answer may help us discriminate who will have a self-limiting course and who will have a persistent course.”

Ms. El-Bouhaddani described MasterMind, a longitudinal cohort study of adolescents drawn from the general population. Each teen completed self-report questionnaires on psychotic experiences and psychosocial problems at two time points over a 2-year period. The study was divided into two phases: a 1-year observational period, followed by an intervention for those at risk, and then a 1-year treatment and follow-up period. She reported only the results of the observational phase.

The study enrolled 1,827 young people, who completed four questionnaires: the Strengths & Difficulties Questionnaire, and questionnaires about psychotic experiences, trauma, and self-esteem. One year later, 1,521 of the participants returned and completed the same surveys.

Ms. El-Bouhaddani constructed four potential pathways from baseline to follow-up: no psychiatric symptoms, remitting symptoms (baseline psychosocial symptoms that remitted by 1 year), incident symptoms (symptoms that appeared only at 1 year), and persistent symptoms (symptoms at both baseline and 1 year). Her goal was to identify any baseline characteristics that might predict a persistent course.

At the 1-year point, the cohort was a mean of 13.5 years old. Most subjects (1,134) had no symptoms at either time point. Incident symptoms were present in 151, remitting symptoms in 181, and persistent symptoms in 46.

Several baseline characteristics significantly separated the group with remitting symptoms from all other groups: They were significantly more likely to have a low education level (61%), to have divorced parents (38%), to report frequent household moves (22%), to have repeated a grade (31%), to report low self-esteem (15%), and to have somatic symptoms (3%). Teens with persistent symptoms also reported more somatic symptoms (3%), but they were significantly more likely than any of the other groups to report having had at least one traumatic event (45%).

At follow-up, psychotic incidents were significantly more common in the remitting and persistent groups (40% and 62%, respectively) than in the nonsymptomatic and incident groups (10% and 11%).

Ms. El-Bouhaddani then broke psychotic experiences down into hallucinations and delusions, and examined their relationships to symptom course. Hallucinations were significantly more common than delusions among those with a persistent course (58% vs. 42%).

She conducted a logistic regression analysis, which determined that any psychotic experience nearly doubled the risk of a persistent course of psychiatric symptoms (OR, 1.92). Hallucinations nearly tripled the risk (OR, 2.74), as did traumatic experiences (OR, 3.0). Delusions increased the risk by close to 60% (OR, 1.59).

The SDQ does not contain questions about psychotic experiences or trauma – the two most powerful predictors of persistent symptoms. It’s time to change this, Ms. El-Bouhaddani said.

“From these results it seems as though we should be asking adolescents about psychotic experiences and trauma. Perhaps it’s time for a new version of the SDQ.”

She had no relevant financial disclosures.

[email protected]

On Twitter @alz_gal

SOURCE: El-Bouhaddani S et al. WPA 2017 Abstract S-023 002.

BERLIN – Teens who reported psychotic symptoms – especially hallucinations – on a baseline mental health screening were twice as likely to develop persistent psychiatric symptoms over the next year as were those without such experiences.

Hallucinations in particular predicted a persistent course, nearly tripling the risk (odds ratio, 2.74), Saliha El-Bouhaddani said at the meeting of the World Psychiatric Association.

“This is quite informative and quite clinically relevant,” said Ms. El-Bouhaddani, a doctoral student in psychology at the Parnassia Group, Rotterdam, the Netherlands. Because mental health symptoms in young people may be self-limiting, it’s not easy to identify which teens are at high risk for developing persistent problems that can predispose them to a full-blown mental disorder. “But we can see here that psychotic experiences may be very useful in detecting which adolescents may have persistency of symptoms. I believe that screening tools for teenagers should involve questions about psychotic symptoms, because the answer may help us discriminate who will have a self-limiting course and who will have a persistent course.”

Ms. El-Bouhaddani described MasterMind, a longitudinal cohort study of adolescents drawn from the general population. Each teen completed self-report questionnaires on psychotic experiences and psychosocial problems at two time points over a 2-year period. The study was divided into two phases: a 1-year observational period, followed by an intervention for those at risk, and then a 1-year treatment and follow-up period. She reported only the results of the observational phase.

The study enrolled 1,827 young people, who completed four questionnaires: the Strengths & Difficulties Questionnaire, and questionnaires about psychotic experiences, trauma, and self-esteem. One year later, 1,521 of the participants returned and completed the same surveys.

Ms. El-Bouhaddani constructed four potential pathways from baseline to follow-up: no psychiatric symptoms, remitting symptoms (baseline psychosocial symptoms that remitted by 1 year), incident symptoms (symptoms that appeared only at 1 year), and persistent symptoms (symptoms at both baseline and 1 year). Her goal was to identify any baseline characteristics that might predict a persistent course.

At the 1-year point, the cohort was a mean of 13.5 years old. Most subjects (1,134) had no symptoms at either time point. Incident symptoms were present in 151, remitting symptoms in 181, and persistent symptoms in 46.

Several baseline characteristics significantly separated the group with remitting symptoms from all other groups: They were significantly more likely to have a low education level (61%), to have divorced parents (38%), to report frequent household moves (22%), to have repeated a grade (31%), to report low self-esteem (15%), and to have somatic symptoms (3%). Teens with persistent symptoms also reported more somatic symptoms (3%), but they were significantly more likely than any of the other groups to report having had at least one traumatic event (45%).

At follow-up, psychotic incidents were significantly more common in the remitting and persistent groups (40% and 62%, respectively) than in the nonsymptomatic and incident groups (10% and 11%).

Ms. El-Bouhaddani then broke psychotic experiences down into hallucinations and delusions, and examined their relationships to symptom course. Hallucinations were significantly more common than delusions among those with a persistent course (58% vs. 42%).

She conducted a logistic regression analysis, which determined that any psychotic experience nearly doubled the risk of a persistent course of psychiatric symptoms (OR, 1.92). Hallucinations nearly tripled the risk (OR, 2.74), as did traumatic experiences (OR, 3.0). Delusions increased the risk by close to 60% (OR, 1.59).

The SDQ does not contain questions about psychotic experiences or trauma – the two most powerful predictors of persistent symptoms. It’s time to change this, Ms. El-Bouhaddani said.

“From these results it seems as though we should be asking adolescents about psychotic experiences and trauma. Perhaps it’s time for a new version of the SDQ.”

She had no relevant financial disclosures.

[email protected]

On Twitter @alz_gal

SOURCE: El-Bouhaddani S et al. WPA 2017 Abstract S-023 002.