HT Staff

Photo courtesy of the CDC

The US Food and Drug Administration (FDA) has launched a new search tool designed to improve access to data in the FDA’s Adverse Event Reporting System (FAERS).

FAERS includes data on adverse events (AEs) associated with drug and biologic products.

The new FAERs public dashboard allows users to search for and organize data by criteria such as drug/biological product, age of the patient, type of AE, year the AE occurred, or within a specific time frame.

The FDA intends for this tool to increase transparency by making it easier for people to see reports the agency receives.

The FDA hopes this, in turn, will spur the submission of more detailed and complete reports from consumers, healthcare professionals, and others.

The FDA uses FAERS for surveillance, such as looking for new safety concerns that might be related to a marketed product, evaluating a manufacturer’s compliance with reporting regulations, and responding to outside requests for information.

The reports in FAERS are evaluated by clinical reviewers in the FDA’s Center for Drug Evaluation and Research and Center for Biologics Evaluation and Research to monitor the safety of products after they are marketed. If a potential safety concern is identified in FAERS, further evaluation is performed.

“Our focus on safety extends beyond approval,” said Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research.

“In fact, our staff spends a lot of time looking at FAERS reports received regarding approved drug and biologic products, and these reports can be very valuable components of our safety assessments. By giving people a better understanding of these data, and the associated limitations, we hope the new interface will encourage people to submit more complete reports.”

The FDA encourages healthcare professionals and consumers to report AEs or quality problems related to drugs and biologics to the FDA’s MedWatch Adverse Event Reporting Program.

In addition to the FAERS database for drugs and biologics, the FDA has AE reporting programs and databases for foods, dietary supplements, and cosmetics (CFSAN Adverse Event Reporting System [CAERS]), medical devices (Manufacturer and User Facility Device Experience [MAUDE]), and vaccines (Vaccine Adverse Event Reporting System [VAERS], which the FDA co-manages with the Centers for Disease Control and Prevention).

Photo courtesy of the CDC

The US Food and Drug Administration (FDA) has launched a new search tool designed to improve access to data in the FDA’s Adverse Event Reporting System (FAERS).

FAERS includes data on adverse events (AEs) associated with drug and biologic products.

The new FAERs public dashboard allows users to search for and organize data by criteria such as drug/biological product, age of the patient, type of AE, year the AE occurred, or within a specific time frame.

The FDA intends for this tool to increase transparency by making it easier for people to see reports the agency receives.

The FDA hopes this, in turn, will spur the submission of more detailed and complete reports from consumers, healthcare professionals, and others.

The FDA uses FAERS for surveillance, such as looking for new safety concerns that might be related to a marketed product, evaluating a manufacturer’s compliance with reporting regulations, and responding to outside requests for information.

The reports in FAERS are evaluated by clinical reviewers in the FDA’s Center for Drug Evaluation and Research and Center for Biologics Evaluation and Research to monitor the safety of products after they are marketed. If a potential safety concern is identified in FAERS, further evaluation is performed.

“Our focus on safety extends beyond approval,” said Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research.

“In fact, our staff spends a lot of time looking at FAERS reports received regarding approved drug and biologic products, and these reports can be very valuable components of our safety assessments. By giving people a better understanding of these data, and the associated limitations, we hope the new interface will encourage people to submit more complete reports.”

The FDA encourages healthcare professionals and consumers to report AEs or quality problems related to drugs and biologics to the FDA’s MedWatch Adverse Event Reporting Program.

In addition to the FAERS database for drugs and biologics, the FDA has AE reporting programs and databases for foods, dietary supplements, and cosmetics (CFSAN Adverse Event Reporting System [CAERS]), medical devices (Manufacturer and User Facility Device Experience [MAUDE]), and vaccines (Vaccine Adverse Event Reporting System [VAERS], which the FDA co-manages with the Centers for Disease Control and Prevention).

Photo courtesy of the CDC

The US Food and Drug Administration (FDA) has launched a new search tool designed to improve access to data in the FDA’s Adverse Event Reporting System (FAERS).

FAERS includes data on adverse events (AEs) associated with drug and biologic products.

The new FAERs public dashboard allows users to search for and organize data by criteria such as drug/biological product, age of the patient, type of AE, year the AE occurred, or within a specific time frame.

The FDA intends for this tool to increase transparency by making it easier for people to see reports the agency receives.

The FDA hopes this, in turn, will spur the submission of more detailed and complete reports from consumers, healthcare professionals, and others.

The FDA uses FAERS for surveillance, such as looking for new safety concerns that might be related to a marketed product, evaluating a manufacturer’s compliance with reporting regulations, and responding to outside requests for information.

The reports in FAERS are evaluated by clinical reviewers in the FDA’s Center for Drug Evaluation and Research and Center for Biologics Evaluation and Research to monitor the safety of products after they are marketed. If a potential safety concern is identified in FAERS, further evaluation is performed.

“Our focus on safety extends beyond approval,” said Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research.

“In fact, our staff spends a lot of time looking at FAERS reports received regarding approved drug and biologic products, and these reports can be very valuable components of our safety assessments. By giving people a better understanding of these data, and the associated limitations, we hope the new interface will encourage people to submit more complete reports.”

The FDA encourages healthcare professionals and consumers to report AEs or quality problems related to drugs and biologics to the FDA’s MedWatch Adverse Event Reporting Program.

In addition to the FAERS database for drugs and biologics, the FDA has AE reporting programs and databases for foods, dietary supplements, and cosmetics (CFSAN Adverse Event Reporting System [CAERS]), medical devices (Manufacturer and User Facility Device Experience [MAUDE]), and vaccines (Vaccine Adverse Event Reporting System [VAERS], which the FDA co-manages with the Centers for Disease Control and Prevention).

Photo by Elise Amendola

New research suggests that, overall, the age of transfused red blood cells (RBCs) does not significantly impact outcomes in critically ill adults, but, in some cases, older RBCs may be the better choice.

The study showed no significant difference in 90-day mortality whether patients received RBCs stored for a mean of 11.8 days or 22.4 days.

Likewise, there were no significant differences in most other study endpoints.

However, febrile nonhemolytic transfusion reactions were more frequent in the short-term storage group.

And among the most severely ill patients, the transfusion of older RBCs was associated with fewer deaths at 90 days.

“Older blood appears to be like a good red wine—better with some age,” said study author D. James Cooper, MD, of Monash University and Alfred Hospital in Melbourne, Victoria, Australia.

“The findings of our trial confirm that the current duration of storage of red blood cells for transfusion is both safe and optimal.”

Dr Cooper and his colleagues reported their findings in NEJM.

The researchers conducted this trial from November 2012 through December 2016 at 59 centers in 5 countries—Australia, New Zealand, Ireland, Finland, and Saudi Arabia.

The study included nearly 5000 critically ill adults who were randomized to receive either the freshest available RBCs or the oldest available RBCs.

There were 2457 patients in the short-term storage group, where the mean RBC storage duration was 11.8 ± 5.3 days. And there were 2462 patients in the long-term storage group, where the mean RBC storage duration was 22.4 ± 7.5 days.

Baseline characteristics were largely similar between the 2 groups. However, patients were significantly older in the short-term storage group, with a mean age of 62.5 ± 16.8 years, compared to 61.4 ± 17.3 years in the long-term storage group (P=0.02).

The median time from randomization to first RBC transfusion was similar between the groups—1.6 hours in the short-term group and 1.5 hours in the long-term group. The mean number of RBC units was also similar—4.1 ± 6.0 and 4.0 ± 6.2, respectively. The use of other blood products was similar as well.

90-day mortality

The study’s primary endpoint was 90-day mortality, which was 24.8% (n=610) in the short-term storage group and 24.1% (n=594) in the long-term storage group. The unadjusted (u) odds ratio (OR) was 1.04 (P=0.57).

When the researchers adjusted for APACHE III risk of death, patient age, hemoglobin at randomization, blood group, and site, the adjusted (a) OR was 1.04 (P=0.59).

When the researchers looked at patient subgroups, they found a significant difference between the storage groups when it came to 90-day mortality according to APACHE III risk of death.

Patients with an APACHE III predicted risk of death at hospital discharge at a median of 21.5% or higher had a significantly higher rate of 90-day mortality if they received the freshest available RBCs rather than the oldest available RBCs—37.7% and 34.0%, respectively (uOR=1.18, P=0.05).

There were no significant differences in 90-day mortality in the other subgroups.

Secondary endpoints

There were no significant between-group differences in secondary endpoints, with the exception of febrile nonhemolytic transfusion reaction. The incidence of this outcome was 5.0% in the short-term storage group and 3.6% in the long-term group (uOR=1.42, P=0.01; aOR=1.45, P=0.01).

Other secondary endpoints included (data in the short-term and long-term groups, respectively):

• Death at day 28 (19.4% and 18.8%, uOR=1.04, P=0.61)
• Death at day 180 (28.5% and 28.1%, uOR=1.02, P=0.75)
• Persistent organ dysfunction or death at day 28 (23.3% and 22.3%, uOR=1.06, P=0.39)
• New bloodstream infection (1.4% and 1.6%, uOR=0.90, P=0.65)
• Duration of hospital stay (median 14.5 days and 14.7 days, P=0.42)
• Duration of stay in the intensive care unit (median 4.2 days for both, P=0.86)
• Invasive mechanical ventilation (58.6% and 59.3%, uOR=0.97, P=0.64)
• Renal-replacement therapy (13.9% and 14.6%, uOR=0.97, P=0.48).
  

Photo by Elise Amendola

New research suggests that, overall, the age of transfused red blood cells (RBCs) does not significantly impact outcomes in critically ill adults, but, in some cases, older RBCs may be the better choice.

The study showed no significant difference in 90-day mortality whether patients received RBCs stored for a mean of 11.8 days or 22.4 days.

Likewise, there were no significant differences in most other study endpoints.

However, febrile nonhemolytic transfusion reactions were more frequent in the short-term storage group.

And among the most severely ill patients, the transfusion of older RBCs was associated with fewer deaths at 90 days.

“Older blood appears to be like a good red wine—better with some age,” said study author D. James Cooper, MD, of Monash University and Alfred Hospital in Melbourne, Victoria, Australia.

“The findings of our trial confirm that the current duration of storage of red blood cells for transfusion is both safe and optimal.”

Dr Cooper and his colleagues reported their findings in NEJM.

The researchers conducted this trial from November 2012 through December 2016 at 59 centers in 5 countries—Australia, New Zealand, Ireland, Finland, and Saudi Arabia.

The study included nearly 5000 critically ill adults who were randomized to receive either the freshest available RBCs or the oldest available RBCs.

There were 2457 patients in the short-term storage group, where the mean RBC storage duration was 11.8 ± 5.3 days. And there were 2462 patients in the long-term storage group, where the mean RBC storage duration was 22.4 ± 7.5 days.

Baseline characteristics were largely similar between the 2 groups. However, patients were significantly older in the short-term storage group, with a mean age of 62.5 ± 16.8 years, compared to 61.4 ± 17.3 years in the long-term storage group (P=0.02).

The median time from randomization to first RBC transfusion was similar between the groups—1.6 hours in the short-term group and 1.5 hours in the long-term group. The mean number of RBC units was also similar—4.1 ± 6.0 and 4.0 ± 6.2, respectively. The use of other blood products was similar as well.

90-day mortality

The study’s primary endpoint was 90-day mortality, which was 24.8% (n=610) in the short-term storage group and 24.1% (n=594) in the long-term storage group. The unadjusted (u) odds ratio (OR) was 1.04 (P=0.57).

When the researchers adjusted for APACHE III risk of death, patient age, hemoglobin at randomization, blood group, and site, the adjusted (a) OR was 1.04 (P=0.59).

When the researchers looked at patient subgroups, they found a significant difference between the storage groups when it came to 90-day mortality according to APACHE III risk of death.

Patients with an APACHE III predicted risk of death at hospital discharge at a median of 21.5% or higher had a significantly higher rate of 90-day mortality if they received the freshest available RBCs rather than the oldest available RBCs—37.7% and 34.0%, respectively (uOR=1.18, P=0.05).

There were no significant differences in 90-day mortality in the other subgroups.

Secondary endpoints

There were no significant between-group differences in secondary endpoints, with the exception of febrile nonhemolytic transfusion reaction. The incidence of this outcome was 5.0% in the short-term storage group and 3.6% in the long-term group (uOR=1.42, P=0.01; aOR=1.45, P=0.01).

Other secondary endpoints included (data in the short-term and long-term groups, respectively):

• Death at day 28 (19.4% and 18.8%, uOR=1.04, P=0.61)
• Death at day 180 (28.5% and 28.1%, uOR=1.02, P=0.75)
• Persistent organ dysfunction or death at day 28 (23.3% and 22.3%, uOR=1.06, P=0.39)
• New bloodstream infection (1.4% and 1.6%, uOR=0.90, P=0.65)
• Duration of hospital stay (median 14.5 days and 14.7 days, P=0.42)
• Duration of stay in the intensive care unit (median 4.2 days for both, P=0.86)
• Invasive mechanical ventilation (58.6% and 59.3%, uOR=0.97, P=0.64)
• Renal-replacement therapy (13.9% and 14.6%, uOR=0.97, P=0.48).
  

Photo by Elise Amendola

New research suggests that, overall, the age of transfused red blood cells (RBCs) does not significantly impact outcomes in critically ill adults, but, in some cases, older RBCs may be the better choice.

The study showed no significant difference in 90-day mortality whether patients received RBCs stored for a mean of 11.8 days or 22.4 days.

Likewise, there were no significant differences in most other study endpoints.

However, febrile nonhemolytic transfusion reactions were more frequent in the short-term storage group.

And among the most severely ill patients, the transfusion of older RBCs was associated with fewer deaths at 90 days.

“Older blood appears to be like a good red wine—better with some age,” said study author D. James Cooper, MD, of Monash University and Alfred Hospital in Melbourne, Victoria, Australia.

“The findings of our trial confirm that the current duration of storage of red blood cells for transfusion is both safe and optimal.”

Dr Cooper and his colleagues reported their findings in NEJM.

The researchers conducted this trial from November 2012 through December 2016 at 59 centers in 5 countries—Australia, New Zealand, Ireland, Finland, and Saudi Arabia.

The study included nearly 5000 critically ill adults who were randomized to receive either the freshest available RBCs or the oldest available RBCs.

There were 2457 patients in the short-term storage group, where the mean RBC storage duration was 11.8 ± 5.3 days. And there were 2462 patients in the long-term storage group, where the mean RBC storage duration was 22.4 ± 7.5 days.

Baseline characteristics were largely similar between the 2 groups. However, patients were significantly older in the short-term storage group, with a mean age of 62.5 ± 16.8 years, compared to 61.4 ± 17.3 years in the long-term storage group (P=0.02).

The median time from randomization to first RBC transfusion was similar between the groups—1.6 hours in the short-term group and 1.5 hours in the long-term group. The mean number of RBC units was also similar—4.1 ± 6.0 and 4.0 ± 6.2, respectively. The use of other blood products was similar as well.

90-day mortality

The study’s primary endpoint was 90-day mortality, which was 24.8% (n=610) in the short-term storage group and 24.1% (n=594) in the long-term storage group. The unadjusted (u) odds ratio (OR) was 1.04 (P=0.57).

When the researchers adjusted for APACHE III risk of death, patient age, hemoglobin at randomization, blood group, and site, the adjusted (a) OR was 1.04 (P=0.59).

When the researchers looked at patient subgroups, they found a significant difference between the storage groups when it came to 90-day mortality according to APACHE III risk of death.

Patients with an APACHE III predicted risk of death at hospital discharge at a median of 21.5% or higher had a significantly higher rate of 90-day mortality if they received the freshest available RBCs rather than the oldest available RBCs—37.7% and 34.0%, respectively (uOR=1.18, P=0.05).

There were no significant differences in 90-day mortality in the other subgroups.

Secondary endpoints

There were no significant between-group differences in secondary endpoints, with the exception of febrile nonhemolytic transfusion reaction. The incidence of this outcome was 5.0% in the short-term storage group and 3.6% in the long-term group (uOR=1.42, P=0.01; aOR=1.45, P=0.01).

Other secondary endpoints included (data in the short-term and long-term groups, respectively):

• Death at day 28 (19.4% and 18.8%, uOR=1.04, P=0.61)
• Death at day 180 (28.5% and 28.1%, uOR=1.02, P=0.75)
• Persistent organ dysfunction or death at day 28 (23.3% and 22.3%, uOR=1.06, P=0.39)
• New bloodstream infection (1.4% and 1.6%, uOR=0.90, P=0.65)
• Duration of hospital stay (median 14.5 days and 14.7 days, P=0.42)
• Duration of stay in the intensive care unit (median 4.2 days for both, P=0.86)
• Invasive mechanical ventilation (58.6% and 59.3%, uOR=0.97, P=0.64)
• Renal-replacement therapy (13.9% and 14.6%, uOR=0.97, P=0.48).
  

Photo courtesy of Janssen

The Ministry of Health, Labor and Welfare in Japan has approved the use of daratumumab (DARZALEX®) in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone to treat adults with relapsed or refractory multiple myeloma (MM).

Daratumumab is a human IgG1k monoclonal antibody that binds to CD38, which is highly expressed on the surface of MM cells.

The drug is being developed by Janssen Biotech, Inc. under an exclusive worldwide license from Genmab.

The approval of daratumumab is based on data from the phase 3 POLLUX and CASTOR trials.

In the POLLUX trial, researchers compared treatment with lenalidomide and dexamethasone to treatment with daratumumab, lenalidomide, and dexamethasone in patients with relapsed or refractory MM.

Patients who received daratumumab in combination had a significantly higher response rate and longer progression-free survival than patients who received the 2-drug combination.

However, treatment with daratumumab was associated with infusion-related reactions and a higher incidence of neutropenia.

Results from this trial were published in NEJM in October 2016.

In the CASTOR trial, researchers compared treatment with bortezomib and dexamethasone to treatment with daratumumab, bortezomib, and dexamethasone in patients with previously treated MM.

Patients who received the 3-drug combination had a higher response rate, longer progression-free survival, and a higher incidence of grade 3/4 adverse events than those who received the 2-drug combination.

Results from this trial were published in NEJM in August 2016.

Photo courtesy of Janssen

The Ministry of Health, Labor and Welfare in Japan has approved the use of daratumumab (DARZALEX®) in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone to treat adults with relapsed or refractory multiple myeloma (MM).

Daratumumab is a human IgG1k monoclonal antibody that binds to CD38, which is highly expressed on the surface of MM cells.

The drug is being developed by Janssen Biotech, Inc. under an exclusive worldwide license from Genmab.

The approval of daratumumab is based on data from the phase 3 POLLUX and CASTOR trials.

In the POLLUX trial, researchers compared treatment with lenalidomide and dexamethasone to treatment with daratumumab, lenalidomide, and dexamethasone in patients with relapsed or refractory MM.

Patients who received daratumumab in combination had a significantly higher response rate and longer progression-free survival than patients who received the 2-drug combination.

However, treatment with daratumumab was associated with infusion-related reactions and a higher incidence of neutropenia.

Results from this trial were published in NEJM in October 2016.

In the CASTOR trial, researchers compared treatment with bortezomib and dexamethasone to treatment with daratumumab, bortezomib, and dexamethasone in patients with previously treated MM.

Patients who received the 3-drug combination had a higher response rate, longer progression-free survival, and a higher incidence of grade 3/4 adverse events than those who received the 2-drug combination.

Results from this trial were published in NEJM in August 2016.

Photo courtesy of Janssen

The Ministry of Health, Labor and Welfare in Japan has approved the use of daratumumab (DARZALEX®) in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone to treat adults with relapsed or refractory multiple myeloma (MM).

Daratumumab is a human IgG1k monoclonal antibody that binds to CD38, which is highly expressed on the surface of MM cells.

The drug is being developed by Janssen Biotech, Inc. under an exclusive worldwide license from Genmab.

The approval of daratumumab is based on data from the phase 3 POLLUX and CASTOR trials.

In the POLLUX trial, researchers compared treatment with lenalidomide and dexamethasone to treatment with daratumumab, lenalidomide, and dexamethasone in patients with relapsed or refractory MM.

Patients who received daratumumab in combination had a significantly higher response rate and longer progression-free survival than patients who received the 2-drug combination.

However, treatment with daratumumab was associated with infusion-related reactions and a higher incidence of neutropenia.

Results from this trial were published in NEJM in October 2016.

In the CASTOR trial, researchers compared treatment with bortezomib and dexamethasone to treatment with daratumumab, bortezomib, and dexamethasone in patients with previously treated MM.

Patients who received the 3-drug combination had a higher response rate, longer progression-free survival, and a higher incidence of grade 3/4 adverse events than those who received the 2-drug combination.

Results from this trial were published in NEJM in August 2016.

Antihemophilic factor

The US Food and Drug Administration (FDA) has granted orphan drug designation to CB 2679d/ISU304, a clinical stage drug candidate for hemophilia B.

CB 2679d/ISU304 is a next-generation coagulation factor IX variant that may allow for subcutaneous prophylactic treatment of patients with hemophilia B.

The product is being developed by Catalyst Biosciences, Inc. and ISU Abxis.

The companies are currently conducting a phase 1/2 trial of CB 2679d/ISU304 in patients with severe hemophilia B.

Catalyst Biosciences and ISU Abxis plan to have interim, top-line results from this trial by the end of 2017 and complete results in early 2018.

CB 2679d/ISU304 also has orphan medicinal product designation from the European Commission.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Antihemophilic factor

The US Food and Drug Administration (FDA) has granted orphan drug designation to CB 2679d/ISU304, a clinical stage drug candidate for hemophilia B.

CB 2679d/ISU304 is a next-generation coagulation factor IX variant that may allow for subcutaneous prophylactic treatment of patients with hemophilia B.

The product is being developed by Catalyst Biosciences, Inc. and ISU Abxis.

The companies are currently conducting a phase 1/2 trial of CB 2679d/ISU304 in patients with severe hemophilia B.

Catalyst Biosciences and ISU Abxis plan to have interim, top-line results from this trial by the end of 2017 and complete results in early 2018.

CB 2679d/ISU304 also has orphan medicinal product designation from the European Commission.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Antihemophilic factor

The US Food and Drug Administration (FDA) has granted orphan drug designation to CB 2679d/ISU304, a clinical stage drug candidate for hemophilia B.

CB 2679d/ISU304 is a next-generation coagulation factor IX variant that may allow for subcutaneous prophylactic treatment of patients with hemophilia B.

The product is being developed by Catalyst Biosciences, Inc. and ISU Abxis.

The companies are currently conducting a phase 1/2 trial of CB 2679d/ISU304 in patients with severe hemophilia B.

Catalyst Biosciences and ISU Abxis plan to have interim, top-line results from this trial by the end of 2017 and complete results in early 2018.

CB 2679d/ISU304 also has orphan medicinal product designation from the European Commission.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Photo from Business Wire

Researchers say they have identified genetic mutations that can significantly affect treatment outcomes in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).

The findings come from a clinical trial in which the team examined whether combining vorinostat with azacitidine could improve survival in patients with AML and MDS.

The results showed no additional benefit with the combination, when compared to azacitidine alone.

However, researchers did find that patients had significantly shorter survival times if they had mutations in CDKN2A, IDH1, or TP53.

“This important trial . . . has rapidly answered the important question of whether combining azacitidine with vorinostat improves outcomes for people with AML and MDS and emphasizes the need for further studies with new drug partners for azacitidine,” said Charles Craddock, DPhil, of the Queen Elizabeth Hospital in Birmingham, UK.

“Importantly, the linked molecular studies have shed new light on which people will benefit most from azacitidine. Furthermore, discovering that the CDKN2A gene mutation affects treatment response may be hugely valuable in helping doctors to design new treatment combinations in the future.”

Dr Craddock and his colleagues reported their discoveries in Clinical Cancer Research.

Previous, smaller trials had suggested that adding vorinostat to treatment with azacitidine could improve outcomes for patients with AML and MDS.

To test this idea, Dr Craddock and his colleagues enrolled 259 patients in the current trial. Most of these patients (n=217) had AML—111 were newly diagnosed, 73 had relapsed AML, and 33 had refractory disease.

The remaining 42 patients had MDS—36 were newly diagnosed, 5 had relapsed MDS, and 1 had refractory disease.

Half of patients (n=130) received azacitidine and vorinostat, and the other half received azacitidine alone (n=129).

In both arms, azacitidine was given at 75 mg/m² on a 5-2-2 schedule, beginning on day 1 of a 28-day cycle for up to 6 cycles. In the combination arm, patients also received vorinostat at 300 mg twice daily for 7 consecutive days, beginning on day 3 of each cycle.

Results

The combination did not significantly improve response rates or survival times.

The overall response rate was 41% in the azacitidine arm and 42% in the combination arm (odds ratio [OR]=1.05, P=0.84).

The rate of compete response (CR)/CR with incomplete count recovery/marrow CR was 22% in the azacitidine arm and 26% in the combination arm (OR=0.82, P=0.49).

The median overall survival (OS) was 9.6 months in the azacitidine arm and 11.0 months in the combination arm (hazard ratio[HR]=1.15, P=0.32).

Impact of mutations

In a multivariable analysis adjusted for all clinical variables, mutations in NPM1 were associated with reduced overall response (OR=8.6, P=0.012).

In another multivariate analysis, mutations in CDKN2A, IDH1, and TP53 were associated with decreased OS. The HRs were 10.0 (P<0.001), 3.6 (P=0.001), and 4.7 (P<0.001), respectively.

The median OS was 4.5 months in patients with CDKN2A mutations and 11.0 months in patients without them.

The median OS was 7.6 months in patients with TP53 mutations and 11.3 months in patients without them.

And the median OS was 5.6 months in patients with IDH1 mutations and 11.1 months in patients without them.

The researchers believe that testing patients newly diagnosed with AML and MDS for CDKN2A, IDH1, and TP53 mutations could help doctors tailor treatment for patients who are less likely to do well.

The team also said the information gleaned from this trial will guide the choice of new drug partners with the potential to increase azacitidine’s clinical activity.

Photo from Business Wire

Researchers say they have identified genetic mutations that can significantly affect treatment outcomes in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).

The findings come from a clinical trial in which the team examined whether combining vorinostat with azacitidine could improve survival in patients with AML and MDS.

The results showed no additional benefit with the combination, when compared to azacitidine alone.

However, researchers did find that patients had significantly shorter survival times if they had mutations in CDKN2A, IDH1, or TP53.

“This important trial . . . has rapidly answered the important question of whether combining azacitidine with vorinostat improves outcomes for people with AML and MDS and emphasizes the need for further studies with new drug partners for azacitidine,” said Charles Craddock, DPhil, of the Queen Elizabeth Hospital in Birmingham, UK.

“Importantly, the linked molecular studies have shed new light on which people will benefit most from azacitidine. Furthermore, discovering that the CDKN2A gene mutation affects treatment response may be hugely valuable in helping doctors to design new treatment combinations in the future.”

Dr Craddock and his colleagues reported their discoveries in Clinical Cancer Research.

Previous, smaller trials had suggested that adding vorinostat to treatment with azacitidine could improve outcomes for patients with AML and MDS.

To test this idea, Dr Craddock and his colleagues enrolled 259 patients in the current trial. Most of these patients (n=217) had AML—111 were newly diagnosed, 73 had relapsed AML, and 33 had refractory disease.

The remaining 42 patients had MDS—36 were newly diagnosed, 5 had relapsed MDS, and 1 had refractory disease.

Half of patients (n=130) received azacitidine and vorinostat, and the other half received azacitidine alone (n=129).

In both arms, azacitidine was given at 75 mg/m² on a 5-2-2 schedule, beginning on day 1 of a 28-day cycle for up to 6 cycles. In the combination arm, patients also received vorinostat at 300 mg twice daily for 7 consecutive days, beginning on day 3 of each cycle.

Results

The combination did not significantly improve response rates or survival times.

The overall response rate was 41% in the azacitidine arm and 42% in the combination arm (odds ratio [OR]=1.05, P=0.84).

The rate of compete response (CR)/CR with incomplete count recovery/marrow CR was 22% in the azacitidine arm and 26% in the combination arm (OR=0.82, P=0.49).

The median overall survival (OS) was 9.6 months in the azacitidine arm and 11.0 months in the combination arm (hazard ratio[HR]=1.15, P=0.32).

Impact of mutations

In a multivariable analysis adjusted for all clinical variables, mutations in NPM1 were associated with reduced overall response (OR=8.6, P=0.012).

In another multivariate analysis, mutations in CDKN2A, IDH1, and TP53 were associated with decreased OS. The HRs were 10.0 (P<0.001), 3.6 (P=0.001), and 4.7 (P<0.001), respectively.

The median OS was 4.5 months in patients with CDKN2A mutations and 11.0 months in patients without them.

The median OS was 7.6 months in patients with TP53 mutations and 11.3 months in patients without them.

And the median OS was 5.6 months in patients with IDH1 mutations and 11.1 months in patients without them.

The researchers believe that testing patients newly diagnosed with AML and MDS for CDKN2A, IDH1, and TP53 mutations could help doctors tailor treatment for patients who are less likely to do well.

The team also said the information gleaned from this trial will guide the choice of new drug partners with the potential to increase azacitidine’s clinical activity.

Photo from Business Wire

Researchers say they have identified genetic mutations that can significantly affect treatment outcomes in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).

The findings come from a clinical trial in which the team examined whether combining vorinostat with azacitidine could improve survival in patients with AML and MDS.

The results showed no additional benefit with the combination, when compared to azacitidine alone.

However, researchers did find that patients had significantly shorter survival times if they had mutations in CDKN2A, IDH1, or TP53.

“This important trial . . . has rapidly answered the important question of whether combining azacitidine with vorinostat improves outcomes for people with AML and MDS and emphasizes the need for further studies with new drug partners for azacitidine,” said Charles Craddock, DPhil, of the Queen Elizabeth Hospital in Birmingham, UK.

“Importantly, the linked molecular studies have shed new light on which people will benefit most from azacitidine. Furthermore, discovering that the CDKN2A gene mutation affects treatment response may be hugely valuable in helping doctors to design new treatment combinations in the future.”

Dr Craddock and his colleagues reported their discoveries in Clinical Cancer Research.

Previous, smaller trials had suggested that adding vorinostat to treatment with azacitidine could improve outcomes for patients with AML and MDS.

To test this idea, Dr Craddock and his colleagues enrolled 259 patients in the current trial. Most of these patients (n=217) had AML—111 were newly diagnosed, 73 had relapsed AML, and 33 had refractory disease.

The remaining 42 patients had MDS—36 were newly diagnosed, 5 had relapsed MDS, and 1 had refractory disease.

Half of patients (n=130) received azacitidine and vorinostat, and the other half received azacitidine alone (n=129).

In both arms, azacitidine was given at 75 mg/m² on a 5-2-2 schedule, beginning on day 1 of a 28-day cycle for up to 6 cycles. In the combination arm, patients also received vorinostat at 300 mg twice daily for 7 consecutive days, beginning on day 3 of each cycle.

Results

The combination did not significantly improve response rates or survival times.

The overall response rate was 41% in the azacitidine arm and 42% in the combination arm (odds ratio [OR]=1.05, P=0.84).

The rate of compete response (CR)/CR with incomplete count recovery/marrow CR was 22% in the azacitidine arm and 26% in the combination arm (OR=0.82, P=0.49).

The median overall survival (OS) was 9.6 months in the azacitidine arm and 11.0 months in the combination arm (hazard ratio[HR]=1.15, P=0.32).

Impact of mutations

In a multivariable analysis adjusted for all clinical variables, mutations in NPM1 were associated with reduced overall response (OR=8.6, P=0.012).

In another multivariate analysis, mutations in CDKN2A, IDH1, and TP53 were associated with decreased OS. The HRs were 10.0 (P<0.001), 3.6 (P=0.001), and 4.7 (P<0.001), respectively.

The median OS was 4.5 months in patients with CDKN2A mutations and 11.0 months in patients without them.

The median OS was 7.6 months in patients with TP53 mutations and 11.3 months in patients without them.

And the median OS was 5.6 months in patients with IDH1 mutations and 11.1 months in patients without them.

The researchers believe that testing patients newly diagnosed with AML and MDS for CDKN2A, IDH1, and TP53 mutations could help doctors tailor treatment for patients who are less likely to do well.

The team also said the information gleaned from this trial will guide the choice of new drug partners with the potential to increase azacitidine’s clinical activity.

Warfarin tablets

Genotype-guided warfarin dosing is safer than clinically guided dosing for patients undergoing elective hip or knee arthroplasty, according to a study published in JAMA.

Investigators found that genotype-guided dosing reduced a patient’s combined risk of experiencing major bleeding, having an international normalized ratio (INR) of 4 or greater, and developing venous thromboembolism (VTE).

Death was also included in this combined endpoint, but there were no deaths in either dosing group.

“Physicians have been prescribing warfarin since the Eisenhower administration,” said study author Brian F. Gage, MD, of Washington University School of Medicine in St. Louis.

“It’s a widely used anticoagulant, but it causes more major adverse events than any other oral drug. Thousands of patients end up in the emergency department or hospital because of warfarin-induced bleeding, but we continue to prescribe it because it is highly effective, reversible, and inexpensive. So our goal is to make warfarin safer.”

With this in mind, Dr Gage and his colleagues set out to determine if genotype-guided dosing would be safer for patients starting warfarin because of elective hip or knee replacement.

The investigators noted that earlier studies of genotype-guided warfarin dosing had produced conflicting results. However, these studies were smaller and included fewer genetic variants than the current trial, known as GIFT.

The GIFT study included 1650 patients, age 65 and older. They were genotyped for the following polymorphisms: VKORC1-1639G>A, CYP2C9*2, CYP2C9*3, and CYP4F2 V433M.

Then, patients were randomized to clinically guided (n=789) or genotype-guided warfarin dosing (n=808) on days 1 through 11 of therapy and to a target INR of either 1.8 or 2.5. (Clinically guided dosing was based on standard factors such as age, height, and weight, while genotype-guided dosing was influenced by clinical factors plus the aforementioned genetic variants.)

Results

The primary endpoint was a combination of major bleeding, INR of 4 or greater, VTE, and death.

This endpoint was met by 10.8% (n=87) of patients in the genotype-guided group and 14.7% (n=116) of patients in the clinically guided warfarin group. The relative rate (RR) was 0.73 (P=0.02).

The incidence of major bleeding on days 1 to 30 was 0.2% (n=2) in the genotype-guided group and 1.0% (n=8) in the clinically guided group. The RR was 0.24 (P=0.06).

The proportion of patients with an INR of 4 or greater on days 1 to 30 was 6.9% (n=56) in the genotype-guided group and 9.8% (n=77) in the clinically guided group. The RR was 2.8 (P=0.04).

The incidence of VTE on days 1 to 60 was similar—4.1% (n=33) in the genotype-guided group and 4.8% the clinically guided group. The RR was 0.85 (P=0.48).

There were no deaths in either group (on days 1 to 30).

The investigators noted that this study has limitations. In particular, the benefits of genotype-guided dosing may differ when applied to patients of other ages or to general clinical practice.

The team also said additional research is needed to determine the cost-effectiveness of personalized warfarin dosing.

“Although genetic testing is more expensive than clinical dosing, the cost is falling,” Dr Gage said. “In our study, we estimated that genetic testing costs less than $200 per person, which is less than 1 month of a newer anticoagulant.”

Finally, the investigators said future studies should assess the impact of additional genetic variants.

“There are additional genetic variants that may help to guide warfarin dosing, especially among patients with African ancestry,” Dr Gage said. “In the future, we hope to quantify how these variants affect warfarin.”

Warfarin tablets

Genotype-guided warfarin dosing is safer than clinically guided dosing for patients undergoing elective hip or knee arthroplasty, according to a study published in JAMA.

Investigators found that genotype-guided dosing reduced a patient’s combined risk of experiencing major bleeding, having an international normalized ratio (INR) of 4 or greater, and developing venous thromboembolism (VTE).

Death was also included in this combined endpoint, but there were no deaths in either dosing group.

“Physicians have been prescribing warfarin since the Eisenhower administration,” said study author Brian F. Gage, MD, of Washington University School of Medicine in St. Louis.

“It’s a widely used anticoagulant, but it causes more major adverse events than any other oral drug. Thousands of patients end up in the emergency department or hospital because of warfarin-induced bleeding, but we continue to prescribe it because it is highly effective, reversible, and inexpensive. So our goal is to make warfarin safer.”

With this in mind, Dr Gage and his colleagues set out to determine if genotype-guided dosing would be safer for patients starting warfarin because of elective hip or knee replacement.

The investigators noted that earlier studies of genotype-guided warfarin dosing had produced conflicting results. However, these studies were smaller and included fewer genetic variants than the current trial, known as GIFT.

The GIFT study included 1650 patients, age 65 and older. They were genotyped for the following polymorphisms: VKORC1-1639G>A, CYP2C9*2, CYP2C9*3, and CYP4F2 V433M.

Then, patients were randomized to clinically guided (n=789) or genotype-guided warfarin dosing (n=808) on days 1 through 11 of therapy and to a target INR of either 1.8 or 2.5. (Clinically guided dosing was based on standard factors such as age, height, and weight, while genotype-guided dosing was influenced by clinical factors plus the aforementioned genetic variants.)

Results

The primary endpoint was a combination of major bleeding, INR of 4 or greater, VTE, and death.

This endpoint was met by 10.8% (n=87) of patients in the genotype-guided group and 14.7% (n=116) of patients in the clinically guided warfarin group. The relative rate (RR) was 0.73 (P=0.02).

The incidence of major bleeding on days 1 to 30 was 0.2% (n=2) in the genotype-guided group and 1.0% (n=8) in the clinically guided group. The RR was 0.24 (P=0.06).

The proportion of patients with an INR of 4 or greater on days 1 to 30 was 6.9% (n=56) in the genotype-guided group and 9.8% (n=77) in the clinically guided group. The RR was 2.8 (P=0.04).

The incidence of VTE on days 1 to 60 was similar—4.1% (n=33) in the genotype-guided group and 4.8% the clinically guided group. The RR was 0.85 (P=0.48).

There were no deaths in either group (on days 1 to 30).

The investigators noted that this study has limitations. In particular, the benefits of genotype-guided dosing may differ when applied to patients of other ages or to general clinical practice.

The team also said additional research is needed to determine the cost-effectiveness of personalized warfarin dosing.

“Although genetic testing is more expensive than clinical dosing, the cost is falling,” Dr Gage said. “In our study, we estimated that genetic testing costs less than $200 per person, which is less than 1 month of a newer anticoagulant.”

Finally, the investigators said future studies should assess the impact of additional genetic variants.

“There are additional genetic variants that may help to guide warfarin dosing, especially among patients with African ancestry,” Dr Gage said. “In the future, we hope to quantify how these variants affect warfarin.”

Warfarin tablets

Genotype-guided warfarin dosing is safer than clinically guided dosing for patients undergoing elective hip or knee arthroplasty, according to a study published in JAMA.

Investigators found that genotype-guided dosing reduced a patient’s combined risk of experiencing major bleeding, having an international normalized ratio (INR) of 4 or greater, and developing venous thromboembolism (VTE).

Death was also included in this combined endpoint, but there were no deaths in either dosing group.

“Physicians have been prescribing warfarin since the Eisenhower administration,” said study author Brian F. Gage, MD, of Washington University School of Medicine in St. Louis.

“It’s a widely used anticoagulant, but it causes more major adverse events than any other oral drug. Thousands of patients end up in the emergency department or hospital because of warfarin-induced bleeding, but we continue to prescribe it because it is highly effective, reversible, and inexpensive. So our goal is to make warfarin safer.”

With this in mind, Dr Gage and his colleagues set out to determine if genotype-guided dosing would be safer for patients starting warfarin because of elective hip or knee replacement.

The investigators noted that earlier studies of genotype-guided warfarin dosing had produced conflicting results. However, these studies were smaller and included fewer genetic variants than the current trial, known as GIFT.

The GIFT study included 1650 patients, age 65 and older. They were genotyped for the following polymorphisms: VKORC1-1639G>A, CYP2C9*2, CYP2C9*3, and CYP4F2 V433M.

Then, patients were randomized to clinically guided (n=789) or genotype-guided warfarin dosing (n=808) on days 1 through 11 of therapy and to a target INR of either 1.8 or 2.5. (Clinically guided dosing was based on standard factors such as age, height, and weight, while genotype-guided dosing was influenced by clinical factors plus the aforementioned genetic variants.)

Results

The primary endpoint was a combination of major bleeding, INR of 4 or greater, VTE, and death.

This endpoint was met by 10.8% (n=87) of patients in the genotype-guided group and 14.7% (n=116) of patients in the clinically guided warfarin group. The relative rate (RR) was 0.73 (P=0.02).

The incidence of major bleeding on days 1 to 30 was 0.2% (n=2) in the genotype-guided group and 1.0% (n=8) in the clinically guided group. The RR was 0.24 (P=0.06).

The proportion of patients with an INR of 4 or greater on days 1 to 30 was 6.9% (n=56) in the genotype-guided group and 9.8% (n=77) in the clinically guided group. The RR was 2.8 (P=0.04).

The incidence of VTE on days 1 to 60 was similar—4.1% (n=33) in the genotype-guided group and 4.8% the clinically guided group. The RR was 0.85 (P=0.48).

There were no deaths in either group (on days 1 to 30).

The investigators noted that this study has limitations. In particular, the benefits of genotype-guided dosing may differ when applied to patients of other ages or to general clinical practice.

The team also said additional research is needed to determine the cost-effectiveness of personalized warfarin dosing.

“Although genetic testing is more expensive than clinical dosing, the cost is falling,” Dr Gage said. “In our study, we estimated that genetic testing costs less than $200 per person, which is less than 1 month of a newer anticoagulant.”

Finally, the investigators said future studies should assess the impact of additional genetic variants.

“There are additional genetic variants that may help to guide warfarin dosing, especially among patients with African ancestry,” Dr Gage said. “In the future, we hope to quantify how these variants affect warfarin.”

Photo by Esther Dyson

ATLANTA—New research suggests some racial/ethnic minority groups are underrepresented in clinical trials for cancer patients in the US.

African-American and Hispanic patients were underrepresented in the trials studied, while Asian and non-Hispanic white patients were not.

Patients belonging to other racial/ethnic groups were not studied in detail.

The research also showed that elderly patients were less likely than other age groups to enroll in a cancer trial.

However, the percentage of elderly patients in the trials studied (36%) was more than double the percentage of elderly individuals in the US population (15.2%).

This research was presented at the 10th AACR Conference on The Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved (abstract A26).

“Clinical trials are crucial in studying the effectiveness of new drugs and ultimately bringing them to the market to benefit patients,” said Narjust Duma, MD, of the Mayo Clinic in Rochester, Minnesota.

“However, many clinical trials lack appropriate representation of certain patient populations. As a result, the findings of a clinical trial might not be generalizable to all patients.”

Dr Duma and her colleagues analyzed enrollment data from all cancer therapeutic trials reported as completed on clinicaltrials.gov from 2003 to 2016. These trials included 55,689 subjects, and the racial/ethnic breakdown of the group was as follows:

• Non-Hispanic white—83%
• African-American—6%
• Asian—5.3%
• Hispanic—2.6%
• “Other”—2.4%.

According to the US Census Bureau, as of July 1, 2016, the estimated total US population was 323,127,516. The racial/ethnic breakdown of that population is as follows:

• White alone (excluding Hispanics/Latinos)—61.3%
• Hispanic/Latino*—17.8%
• Black/African-American alone—13.3%
• Asian alone—5.7%
• American Indian/Alaska Native—1.3%
• Native Hawaiian/Other Pacific Islander—0.2%
• Two or more races—2.6%.

Dr Duma and her colleagues said their study suggests African-American and Hispanic representation in cancer trials has declined in recent years, when compared to historical data from 1996 to 2002.

In the 1996-2002 period, African-Americans represented 9.2% of patients in cancer trials (vs 6% in 2003-2016), and Hispanics represented 3.1% (vs 2.6% in 2003-2016).

On the other hand, the recruitment of Asians in cancer trials has more than doubled, from 2% in the historical data to 5.3% in the current data.

The current study also showed that elderly patients (age 65 and older) represented 36% of the subjects enrolled in cancer trials. In comparison, 15.2% of the total US population is 65 or older.

Previous research suggested the elderly are often underrepresented in clinical trials, despite the fact that most cancer cases are diagnosed in individuals age 65 and older, according to the National Cancer Institute’s Surveillance, Epidemiology and End Results database.

Dr Duma said the increasing use of genetic information in clinical trials may be decreasing the numbers of ethnic minorities and elderly patients. In recent years, researchers have sought to study drugs that treat cancers by targeting certain mutations. In order to identify the patients who are most likely to respond to the drugs, many trials now require molecular testing of tumors.

“This is leading to significant advances,” Dr Duma said. “However, it is vastly more expensive to run these trials, often leaving a limited budget to recruit patients or do outreach to the elderly or minorities.”

“Also, this type of testing can only be conducted at the major cancer centers. The mid-sized, regional hospitals are excluded because they don’t have the capacity, and, sadly, this leaves us farther away from these populations.”

Dr Duma added that cultural biases may also make minorities less likely to enroll in clinical trials. Previous research has indicated that members of certain minority groups may be less likely to trust healthcare providers.

Language barriers may also be a factor for minority patients, and the elderly may be dissuaded by difficulty in traveling to and from major cancer centers, Dr Duma noted.

She identified a few potential ways to narrow the gap of participation in clinical trials:

• Increase clinical trial partnerships between major cancer centers and satellite hospitals. Dr Duma suggested that patients could be enrolled at their local hospital and undergo treatment there, while data could be sent to the partnering cancer center.
• Targeted interventions, such as Spanish interpreters, could be used to help enroll minority patients in clinical trials.
• Healthcare providers should be mindful of the need to enroll more patients from underrepresented populations and should be willing to discuss risks and benefits with patients.

Dr Duma said the main limitation of this study is that race and ethnicity are generally self-reported, which could lead to some inconsistencies in data.

*The US Census Bureau notes that Hispanics may be of any race, so they are also included in applicable race categories.

Photo by Esther Dyson

ATLANTA—New research suggests some racial/ethnic minority groups are underrepresented in clinical trials for cancer patients in the US.

African-American and Hispanic patients were underrepresented in the trials studied, while Asian and non-Hispanic white patients were not.

Patients belonging to other racial/ethnic groups were not studied in detail.

The research also showed that elderly patients were less likely than other age groups to enroll in a cancer trial.

However, the percentage of elderly patients in the trials studied (36%) was more than double the percentage of elderly individuals in the US population (15.2%).

This research was presented at the 10th AACR Conference on The Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved (abstract A26).

“Clinical trials are crucial in studying the effectiveness of new drugs and ultimately bringing them to the market to benefit patients,” said Narjust Duma, MD, of the Mayo Clinic in Rochester, Minnesota.

“However, many clinical trials lack appropriate representation of certain patient populations. As a result, the findings of a clinical trial might not be generalizable to all patients.”

Dr Duma and her colleagues analyzed enrollment data from all cancer therapeutic trials reported as completed on clinicaltrials.gov from 2003 to 2016. These trials included 55,689 subjects, and the racial/ethnic breakdown of the group was as follows:

• Non-Hispanic white—83%
• African-American—6%
• Asian—5.3%
• Hispanic—2.6%
• “Other”—2.4%.

According to the US Census Bureau, as of July 1, 2016, the estimated total US population was 323,127,516. The racial/ethnic breakdown of that population is as follows:

• White alone (excluding Hispanics/Latinos)—61.3%
• Hispanic/Latino*—17.8%
• Black/African-American alone—13.3%
• Asian alone—5.7%
• American Indian/Alaska Native—1.3%
• Native Hawaiian/Other Pacific Islander—0.2%
• Two or more races—2.6%.

Dr Duma and her colleagues said their study suggests African-American and Hispanic representation in cancer trials has declined in recent years, when compared to historical data from 1996 to 2002.

In the 1996-2002 period, African-Americans represented 9.2% of patients in cancer trials (vs 6% in 2003-2016), and Hispanics represented 3.1% (vs 2.6% in 2003-2016).

On the other hand, the recruitment of Asians in cancer trials has more than doubled, from 2% in the historical data to 5.3% in the current data.

The current study also showed that elderly patients (age 65 and older) represented 36% of the subjects enrolled in cancer trials. In comparison, 15.2% of the total US population is 65 or older.

Previous research suggested the elderly are often underrepresented in clinical trials, despite the fact that most cancer cases are diagnosed in individuals age 65 and older, according to the National Cancer Institute’s Surveillance, Epidemiology and End Results database.

Dr Duma said the increasing use of genetic information in clinical trials may be decreasing the numbers of ethnic minorities and elderly patients. In recent years, researchers have sought to study drugs that treat cancers by targeting certain mutations. In order to identify the patients who are most likely to respond to the drugs, many trials now require molecular testing of tumors.

“This is leading to significant advances,” Dr Duma said. “However, it is vastly more expensive to run these trials, often leaving a limited budget to recruit patients or do outreach to the elderly or minorities.”

“Also, this type of testing can only be conducted at the major cancer centers. The mid-sized, regional hospitals are excluded because they don’t have the capacity, and, sadly, this leaves us farther away from these populations.”

Dr Duma added that cultural biases may also make minorities less likely to enroll in clinical trials. Previous research has indicated that members of certain minority groups may be less likely to trust healthcare providers.

Language barriers may also be a factor for minority patients, and the elderly may be dissuaded by difficulty in traveling to and from major cancer centers, Dr Duma noted.

She identified a few potential ways to narrow the gap of participation in clinical trials:

• Increase clinical trial partnerships between major cancer centers and satellite hospitals. Dr Duma suggested that patients could be enrolled at their local hospital and undergo treatment there, while data could be sent to the partnering cancer center.
• Targeted interventions, such as Spanish interpreters, could be used to help enroll minority patients in clinical trials.
• Healthcare providers should be mindful of the need to enroll more patients from underrepresented populations and should be willing to discuss risks and benefits with patients.

Dr Duma said the main limitation of this study is that race and ethnicity are generally self-reported, which could lead to some inconsistencies in data.

*The US Census Bureau notes that Hispanics may be of any race, so they are also included in applicable race categories.

Photo by Esther Dyson

ATLANTA—New research suggests some racial/ethnic minority groups are underrepresented in clinical trials for cancer patients in the US.

African-American and Hispanic patients were underrepresented in the trials studied, while Asian and non-Hispanic white patients were not.

Patients belonging to other racial/ethnic groups were not studied in detail.

The research also showed that elderly patients were less likely than other age groups to enroll in a cancer trial.

However, the percentage of elderly patients in the trials studied (36%) was more than double the percentage of elderly individuals in the US population (15.2%).

This research was presented at the 10th AACR Conference on The Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved (abstract A26).

“Clinical trials are crucial in studying the effectiveness of new drugs and ultimately bringing them to the market to benefit patients,” said Narjust Duma, MD, of the Mayo Clinic in Rochester, Minnesota.

“However, many clinical trials lack appropriate representation of certain patient populations. As a result, the findings of a clinical trial might not be generalizable to all patients.”

Dr Duma and her colleagues analyzed enrollment data from all cancer therapeutic trials reported as completed on clinicaltrials.gov from 2003 to 2016. These trials included 55,689 subjects, and the racial/ethnic breakdown of the group was as follows:

• Non-Hispanic white—83%
• African-American—6%
• Asian—5.3%
• Hispanic—2.6%
• “Other”—2.4%.

According to the US Census Bureau, as of July 1, 2016, the estimated total US population was 323,127,516. The racial/ethnic breakdown of that population is as follows:

• White alone (excluding Hispanics/Latinos)—61.3%
• Hispanic/Latino*—17.8%
• Black/African-American alone—13.3%
• Asian alone—5.7%
• American Indian/Alaska Native—1.3%
• Native Hawaiian/Other Pacific Islander—0.2%
• Two or more races—2.6%.

Dr Duma and her colleagues said their study suggests African-American and Hispanic representation in cancer trials has declined in recent years, when compared to historical data from 1996 to 2002.

In the 1996-2002 period, African-Americans represented 9.2% of patients in cancer trials (vs 6% in 2003-2016), and Hispanics represented 3.1% (vs 2.6% in 2003-2016).

On the other hand, the recruitment of Asians in cancer trials has more than doubled, from 2% in the historical data to 5.3% in the current data.

The current study also showed that elderly patients (age 65 and older) represented 36% of the subjects enrolled in cancer trials. In comparison, 15.2% of the total US population is 65 or older.

Previous research suggested the elderly are often underrepresented in clinical trials, despite the fact that most cancer cases are diagnosed in individuals age 65 and older, according to the National Cancer Institute’s Surveillance, Epidemiology and End Results database.

Dr Duma said the increasing use of genetic information in clinical trials may be decreasing the numbers of ethnic minorities and elderly patients. In recent years, researchers have sought to study drugs that treat cancers by targeting certain mutations. In order to identify the patients who are most likely to respond to the drugs, many trials now require molecular testing of tumors.

“This is leading to significant advances,” Dr Duma said. “However, it is vastly more expensive to run these trials, often leaving a limited budget to recruit patients or do outreach to the elderly or minorities.”

“Also, this type of testing can only be conducted at the major cancer centers. The mid-sized, regional hospitals are excluded because they don’t have the capacity, and, sadly, this leaves us farther away from these populations.”

Dr Duma added that cultural biases may also make minorities less likely to enroll in clinical trials. Previous research has indicated that members of certain minority groups may be less likely to trust healthcare providers.

Language barriers may also be a factor for minority patients, and the elderly may be dissuaded by difficulty in traveling to and from major cancer centers, Dr Duma noted.

She identified a few potential ways to narrow the gap of participation in clinical trials:

• Increase clinical trial partnerships between major cancer centers and satellite hospitals. Dr Duma suggested that patients could be enrolled at their local hospital and undergo treatment there, while data could be sent to the partnering cancer center.
• Targeted interventions, such as Spanish interpreters, could be used to help enroll minority patients in clinical trials.
• Healthcare providers should be mindful of the need to enroll more patients from underrepresented populations and should be willing to discuss risks and benefits with patients.

Dr Duma said the main limitation of this study is that race and ethnicity are generally self-reported, which could lead to some inconsistencies in data.

*The US Census Bureau notes that Hispanics may be of any race, so they are also included in applicable race categories.

Photo by Rhoda Baer

A new study suggests cancer patients may be open to using marijuana, but healthcare providers may be falling short in educating patients on marijuana use.

This single-center study included more than 900 cancer patients in a US state with legalized medicinal and recreational marijuana.

More than 90% of the patients surveyed said they were interested in learning more about marijuana use in the context of cancer, and nearly three-quarters of the patients wanted their cancer care providers to supply information on the topic.

However, less than 15% of patients received such information from providers. Instead, patients learned about marijuana use from sources such as the Internet or other patients.

“Cancer patients desire but are not receiving information from their cancer doctors about marijuana use during their treatment, so many of them are seeking information from alternate, non-scientific sources,” said Steven Pergam, MD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington.

Dr Pergam and his colleagues reported this finding in the journal Cancer.

Eight US states and the District of Columbia have legalized recreational marijuana, and more than half of states have passed laws allowing for medical marijuana in some form. Marijuana is purported to alleviate symptoms related to cancer treatment, but patterns of use among cancer patients are not well known.

To investigate, Dr Pergam and his colleagues surveyed 926 patients at the Seattle Cancer Center Alliance. The patients’ median age was 58, 52% were male, and 59% had at least a college degree. Thirty-four percent of patients had hematologic malignancies.

Results

Sixty-six percent of patients said they had used marijuana in the past, 24% used in the last year, and 21% used in the last month.

A random analysis of patient urine samples showed that 14% of patients had evidence of recent marijuana use, similar to the 18% of users who reported at least weekly marijuana use.

When compared to patients who never used marijuana and those who previously used marijuana but quit, patients currently using marijuana said they were more likely to do so because the drug had been legalized. Women were more likely than men to use because of legalization.

Current marijuana users were younger, had less education, and were less likely to have undergone hematopoietic stem cell transplant. There was no difference in marijuana use according to a patient’s cancer type.

Most patients said they used marijuana to relieve physical symptoms (75%) and neuropsychiatric symptoms (63%), though some also used it recreationally (35%).

In addition, 26% of current marijuana users said they believed the drug was helping to treat their cancer. And 5% of these users said this was their only reason for marijuana use.

Most patients (92%) said they wanted to learn more about marijuana and cancer. However, the level of interest varied with age, with younger patients expressing the most interest.

Seventy-four percent of patients said they would prefer to get information on marijuana use from their cancer team, but less than 15% received such information from their cancer physician or nurse.

Patients said they received information on marijuana and cancer from friends and family, newspaper and magazine articles, websites and blogs, or another cancer patient.

More than a third of patients said they had not received any information on marijuana and cancer.

“We hope that this study helps to open up the door for more studies aimed at evaluating the risks and benefits of marijuana in this population,” Dr Pergam said. “This is important because if we do not educate our patients about marijuana, they will continue to get their information elsewhere.”

Photo by Rhoda Baer

A new study suggests cancer patients may be open to using marijuana, but healthcare providers may be falling short in educating patients on marijuana use.

This single-center study included more than 900 cancer patients in a US state with legalized medicinal and recreational marijuana.

More than 90% of the patients surveyed said they were interested in learning more about marijuana use in the context of cancer, and nearly three-quarters of the patients wanted their cancer care providers to supply information on the topic.

However, less than 15% of patients received such information from providers. Instead, patients learned about marijuana use from sources such as the Internet or other patients.

“Cancer patients desire but are not receiving information from their cancer doctors about marijuana use during their treatment, so many of them are seeking information from alternate, non-scientific sources,” said Steven Pergam, MD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington.

Dr Pergam and his colleagues reported this finding in the journal Cancer.

Eight US states and the District of Columbia have legalized recreational marijuana, and more than half of states have passed laws allowing for medical marijuana in some form. Marijuana is purported to alleviate symptoms related to cancer treatment, but patterns of use among cancer patients are not well known.

To investigate, Dr Pergam and his colleagues surveyed 926 patients at the Seattle Cancer Center Alliance. The patients’ median age was 58, 52% were male, and 59% had at least a college degree. Thirty-four percent of patients had hematologic malignancies.

Results

Sixty-six percent of patients said they had used marijuana in the past, 24% used in the last year, and 21% used in the last month.

A random analysis of patient urine samples showed that 14% of patients had evidence of recent marijuana use, similar to the 18% of users who reported at least weekly marijuana use.

When compared to patients who never used marijuana and those who previously used marijuana but quit, patients currently using marijuana said they were more likely to do so because the drug had been legalized. Women were more likely than men to use because of legalization.

Current marijuana users were younger, had less education, and were less likely to have undergone hematopoietic stem cell transplant. There was no difference in marijuana use according to a patient’s cancer type.

Most patients said they used marijuana to relieve physical symptoms (75%) and neuropsychiatric symptoms (63%), though some also used it recreationally (35%).

In addition, 26% of current marijuana users said they believed the drug was helping to treat their cancer. And 5% of these users said this was their only reason for marijuana use.

Most patients (92%) said they wanted to learn more about marijuana and cancer. However, the level of interest varied with age, with younger patients expressing the most interest.

Seventy-four percent of patients said they would prefer to get information on marijuana use from their cancer team, but less than 15% received such information from their cancer physician or nurse.

Patients said they received information on marijuana and cancer from friends and family, newspaper and magazine articles, websites and blogs, or another cancer patient.

More than a third of patients said they had not received any information on marijuana and cancer.

“We hope that this study helps to open up the door for more studies aimed at evaluating the risks and benefits of marijuana in this population,” Dr Pergam said. “This is important because if we do not educate our patients about marijuana, they will continue to get their information elsewhere.”

Photo by Rhoda Baer

A new study suggests cancer patients may be open to using marijuana, but healthcare providers may be falling short in educating patients on marijuana use.

This single-center study included more than 900 cancer patients in a US state with legalized medicinal and recreational marijuana.

More than 90% of the patients surveyed said they were interested in learning more about marijuana use in the context of cancer, and nearly three-quarters of the patients wanted their cancer care providers to supply information on the topic.

However, less than 15% of patients received such information from providers. Instead, patients learned about marijuana use from sources such as the Internet or other patients.

“Cancer patients desire but are not receiving information from their cancer doctors about marijuana use during their treatment, so many of them are seeking information from alternate, non-scientific sources,” said Steven Pergam, MD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington.

Dr Pergam and his colleagues reported this finding in the journal Cancer.

Eight US states and the District of Columbia have legalized recreational marijuana, and more than half of states have passed laws allowing for medical marijuana in some form. Marijuana is purported to alleviate symptoms related to cancer treatment, but patterns of use among cancer patients are not well known.

To investigate, Dr Pergam and his colleagues surveyed 926 patients at the Seattle Cancer Center Alliance. The patients’ median age was 58, 52% were male, and 59% had at least a college degree. Thirty-four percent of patients had hematologic malignancies.

Results

Sixty-six percent of patients said they had used marijuana in the past, 24% used in the last year, and 21% used in the last month.

A random analysis of patient urine samples showed that 14% of patients had evidence of recent marijuana use, similar to the 18% of users who reported at least weekly marijuana use.

When compared to patients who never used marijuana and those who previously used marijuana but quit, patients currently using marijuana said they were more likely to do so because the drug had been legalized. Women were more likely than men to use because of legalization.

Current marijuana users were younger, had less education, and were less likely to have undergone hematopoietic stem cell transplant. There was no difference in marijuana use according to a patient’s cancer type.

Most patients said they used marijuana to relieve physical symptoms (75%) and neuropsychiatric symptoms (63%), though some also used it recreationally (35%).

In addition, 26% of current marijuana users said they believed the drug was helping to treat their cancer. And 5% of these users said this was their only reason for marijuana use.

Most patients (92%) said they wanted to learn more about marijuana and cancer. However, the level of interest varied with age, with younger patients expressing the most interest.

Seventy-four percent of patients said they would prefer to get information on marijuana use from their cancer team, but less than 15% received such information from their cancer physician or nurse.

Patients said they received information on marijuana and cancer from friends and family, newspaper and magazine articles, websites and blogs, or another cancer patient.

More than a third of patients said they had not received any information on marijuana and cancer.

“We hope that this study helps to open up the door for more studies aimed at evaluating the risks and benefits of marijuana in this population,” Dr Pergam said. “This is important because if we do not educate our patients about marijuana, they will continue to get their information elsewhere.”

Micrograph showing MF

Results of the SIMPLIFY-1 study revealed how 2 JAK inhibitors—momelotinib and ruxolitinib—compared to one another in myelofibrosis (MF) patients who were previously JAK-inhibitor-naïve.

Momelotinib proved noninferior to ruxolitinib when it came to spleen reduction but not symptom response.

On the other hand, momelotinib was more effective than ruxolitinib in reducing transfusion dependence.

The overall incidence of adverse events (AEs) was similar between the treatment arms.

However, patients receiving momelotinib were more likely to experience AEs leading to treatment discontinuation.

Ruben A. Mesa, MD, of Mayo Clinic Cancer Center in Phoenix, Arizona, and his colleagues reported these results in the Journal of Clinical Oncology. The study was sponsored by Gilead Sciences.

SIMPLIFY-1 was a phase 3, double-blind, active-controlled study. It enrolled 432 patients with symptomatic intermediate-1-risk MF, intermediate-2-risk MF, or high-risk MF.

These JAK-inhibitor-naïve patients were randomized to receive 24 weeks of treatment with momelotinib (n=215, 200 mg once daily) or ruxolitinib (n=217, 20 mg twice a day or per label). After that, all patients could receive open-label momelotinib.

The researchers said baseline characteristics were similar between the treatment arms. In the overall cohort, most patients were white (82.6%), male (56.5%), 65 or older (57.2%), and had primary MF (56.5%).

In all, 376 patients completed 24 weeks of treatment—175 in the momelotinib arm and 201 in the ruxolitinib arm. And 368 patients proceeded to the open-label phase of the study—171 from the momelotinib arm and 197 from the ruxolitinib arm (who switched to momelotinib).

Efficacy

The primary efficacy endpoint was spleen response rate at 24 weeks, which was defined as the proportion of patients achieving at least a 35% reduction in spleen volume.

This endpoint was achieved by a similar proportion of patients in both treatment arms—26.5% in the momelotinib arm and 29% in the ruxolitinib arm. This met the criteria for noninferiority (P=0.011).

On the other hand, noninferiority was not met for total symptom score, which was the proportion of patients achieving at least a 50% reduction in MF symptoms. This endpoint was achieved by 28.4% in the momelotinib arm and 42.2% in the ruxolitinib arm (P=0.98 for noninferiority).

A greater proportion of patients were transfusion-independent at week 24 in the momelotinib arm than the ruxolitinib arm—66.5% and 49.3%, respectively (nominal P<0.001).

The median rate of red blood cell transfusion was 0 units per month in the momelotinib arm and 0.4 units per month in the ruxolitinib arm (nominal P<0.001).

Safety

Most patients had at least 1 AE—92.1% in the momelotinib arm and 95.4% in the ruxolitinib arm. Grade 3 or higher AEs occurred in 35.5% and 43.5%, respectively.

Serious AEs occurred in 22.9% and 18.1%, respectively. AEs leading to treatment discontinuation occurred in 13.1% and 5.6%, respectively.

Treatment-emergent AEs occurring in at least 10% of patients in either treatment arm (momelotinib and ruxolitinib, respectively) were thrombocytopenia (18.7% and 29.2%), diarrhea (17.8% and 19.9%), headache (17.3% and 19.9%), dizziness (15.9% and 11.6%), nausea (15.9% and 3.7%), fatigue (14.5% and 12.0%), anemia (13.6% and 38%), abdominal pain (10.3% and 11.1%), and peripheral neuropathy (10.3% and 4.6%).

The most common grade 3/4 AEs in the momelotinib arm were thrombocytopenia (7.0%), anemia (5.6%), diarrhea (2.8%), hypertension (2.8%), and neutropenia (2.8%).

The most common grade 3/4 AEs in the ruxolitinib arm were anemia (23.1%), neutropenia (4.6%), thrombocytopenia (4.6%), and hypertension (4.2%).

There were 7 deaths in the momelotinib arm. The causes of death were listed as enteritis, mesenteric vein thrombosis, death, sudden death, sepsis, renal failure, and aortic dissection.

There were 7 deaths in the ruxolitinib arm as well. The causes of death were melena, sepsis, pneumonia, head injury, acute myeloid leukemia, recurrent mantle cell lymphoma, and coma.

Transformation to acute myeloid leukemia occurred in 1 patient in the momelotinib arm (grade 4) and 2 patients in the ruxolitinib arm (grade 3 and grade 5).

Micrograph showing MF

Results of the SIMPLIFY-1 study revealed how 2 JAK inhibitors—momelotinib and ruxolitinib—compared to one another in myelofibrosis (MF) patients who were previously JAK-inhibitor-naïve.

Momelotinib proved noninferior to ruxolitinib when it came to spleen reduction but not symptom response.

On the other hand, momelotinib was more effective than ruxolitinib in reducing transfusion dependence.

The overall incidence of adverse events (AEs) was similar between the treatment arms.

However, patients receiving momelotinib were more likely to experience AEs leading to treatment discontinuation.

Ruben A. Mesa, MD, of Mayo Clinic Cancer Center in Phoenix, Arizona, and his colleagues reported these results in the Journal of Clinical Oncology. The study was sponsored by Gilead Sciences.

SIMPLIFY-1 was a phase 3, double-blind, active-controlled study. It enrolled 432 patients with symptomatic intermediate-1-risk MF, intermediate-2-risk MF, or high-risk MF.

These JAK-inhibitor-naïve patients were randomized to receive 24 weeks of treatment with momelotinib (n=215, 200 mg once daily) or ruxolitinib (n=217, 20 mg twice a day or per label). After that, all patients could receive open-label momelotinib.

The researchers said baseline characteristics were similar between the treatment arms. In the overall cohort, most patients were white (82.6%), male (56.5%), 65 or older (57.2%), and had primary MF (56.5%).

In all, 376 patients completed 24 weeks of treatment—175 in the momelotinib arm and 201 in the ruxolitinib arm. And 368 patients proceeded to the open-label phase of the study—171 from the momelotinib arm and 197 from the ruxolitinib arm (who switched to momelotinib).

Efficacy

The primary efficacy endpoint was spleen response rate at 24 weeks, which was defined as the proportion of patients achieving at least a 35% reduction in spleen volume.

This endpoint was achieved by a similar proportion of patients in both treatment arms—26.5% in the momelotinib arm and 29% in the ruxolitinib arm. This met the criteria for noninferiority (P=0.011).

On the other hand, noninferiority was not met for total symptom score, which was the proportion of patients achieving at least a 50% reduction in MF symptoms. This endpoint was achieved by 28.4% in the momelotinib arm and 42.2% in the ruxolitinib arm (P=0.98 for noninferiority).

A greater proportion of patients were transfusion-independent at week 24 in the momelotinib arm than the ruxolitinib arm—66.5% and 49.3%, respectively (nominal P<0.001).

The median rate of red blood cell transfusion was 0 units per month in the momelotinib arm and 0.4 units per month in the ruxolitinib arm (nominal P<0.001).

Safety

Most patients had at least 1 AE—92.1% in the momelotinib arm and 95.4% in the ruxolitinib arm. Grade 3 or higher AEs occurred in 35.5% and 43.5%, respectively.

Serious AEs occurred in 22.9% and 18.1%, respectively. AEs leading to treatment discontinuation occurred in 13.1% and 5.6%, respectively.

Treatment-emergent AEs occurring in at least 10% of patients in either treatment arm (momelotinib and ruxolitinib, respectively) were thrombocytopenia (18.7% and 29.2%), diarrhea (17.8% and 19.9%), headache (17.3% and 19.9%), dizziness (15.9% and 11.6%), nausea (15.9% and 3.7%), fatigue (14.5% and 12.0%), anemia (13.6% and 38%), abdominal pain (10.3% and 11.1%), and peripheral neuropathy (10.3% and 4.6%).

The most common grade 3/4 AEs in the momelotinib arm were thrombocytopenia (7.0%), anemia (5.6%), diarrhea (2.8%), hypertension (2.8%), and neutropenia (2.8%).

The most common grade 3/4 AEs in the ruxolitinib arm were anemia (23.1%), neutropenia (4.6%), thrombocytopenia (4.6%), and hypertension (4.2%).

There were 7 deaths in the momelotinib arm. The causes of death were listed as enteritis, mesenteric vein thrombosis, death, sudden death, sepsis, renal failure, and aortic dissection.

There were 7 deaths in the ruxolitinib arm as well. The causes of death were melena, sepsis, pneumonia, head injury, acute myeloid leukemia, recurrent mantle cell lymphoma, and coma.

Transformation to acute myeloid leukemia occurred in 1 patient in the momelotinib arm (grade 4) and 2 patients in the ruxolitinib arm (grade 3 and grade 5).

Micrograph showing MF

Results of the SIMPLIFY-1 study revealed how 2 JAK inhibitors—momelotinib and ruxolitinib—compared to one another in myelofibrosis (MF) patients who were previously JAK-inhibitor-naïve.

Momelotinib proved noninferior to ruxolitinib when it came to spleen reduction but not symptom response.

On the other hand, momelotinib was more effective than ruxolitinib in reducing transfusion dependence.

The overall incidence of adverse events (AEs) was similar between the treatment arms.

However, patients receiving momelotinib were more likely to experience AEs leading to treatment discontinuation.

Ruben A. Mesa, MD, of Mayo Clinic Cancer Center in Phoenix, Arizona, and his colleagues reported these results in the Journal of Clinical Oncology. The study was sponsored by Gilead Sciences.

SIMPLIFY-1 was a phase 3, double-blind, active-controlled study. It enrolled 432 patients with symptomatic intermediate-1-risk MF, intermediate-2-risk MF, or high-risk MF.

These JAK-inhibitor-naïve patients were randomized to receive 24 weeks of treatment with momelotinib (n=215, 200 mg once daily) or ruxolitinib (n=217, 20 mg twice a day or per label). After that, all patients could receive open-label momelotinib.

The researchers said baseline characteristics were similar between the treatment arms. In the overall cohort, most patients were white (82.6%), male (56.5%), 65 or older (57.2%), and had primary MF (56.5%).

In all, 376 patients completed 24 weeks of treatment—175 in the momelotinib arm and 201 in the ruxolitinib arm. And 368 patients proceeded to the open-label phase of the study—171 from the momelotinib arm and 197 from the ruxolitinib arm (who switched to momelotinib).

Efficacy

The primary efficacy endpoint was spleen response rate at 24 weeks, which was defined as the proportion of patients achieving at least a 35% reduction in spleen volume.

This endpoint was achieved by a similar proportion of patients in both treatment arms—26.5% in the momelotinib arm and 29% in the ruxolitinib arm. This met the criteria for noninferiority (P=0.011).

On the other hand, noninferiority was not met for total symptom score, which was the proportion of patients achieving at least a 50% reduction in MF symptoms. This endpoint was achieved by 28.4% in the momelotinib arm and 42.2% in the ruxolitinib arm (P=0.98 for noninferiority).

A greater proportion of patients were transfusion-independent at week 24 in the momelotinib arm than the ruxolitinib arm—66.5% and 49.3%, respectively (nominal P<0.001).

The median rate of red blood cell transfusion was 0 units per month in the momelotinib arm and 0.4 units per month in the ruxolitinib arm (nominal P<0.001).

Safety

Most patients had at least 1 AE—92.1% in the momelotinib arm and 95.4% in the ruxolitinib arm. Grade 3 or higher AEs occurred in 35.5% and 43.5%, respectively.

Serious AEs occurred in 22.9% and 18.1%, respectively. AEs leading to treatment discontinuation occurred in 13.1% and 5.6%, respectively.

Treatment-emergent AEs occurring in at least 10% of patients in either treatment arm (momelotinib and ruxolitinib, respectively) were thrombocytopenia (18.7% and 29.2%), diarrhea (17.8% and 19.9%), headache (17.3% and 19.9%), dizziness (15.9% and 11.6%), nausea (15.9% and 3.7%), fatigue (14.5% and 12.0%), anemia (13.6% and 38%), abdominal pain (10.3% and 11.1%), and peripheral neuropathy (10.3% and 4.6%).

The most common grade 3/4 AEs in the momelotinib arm were thrombocytopenia (7.0%), anemia (5.6%), diarrhea (2.8%), hypertension (2.8%), and neutropenia (2.8%).

The most common grade 3/4 AEs in the ruxolitinib arm were anemia (23.1%), neutropenia (4.6%), thrombocytopenia (4.6%), and hypertension (4.2%).

There were 7 deaths in the momelotinib arm. The causes of death were listed as enteritis, mesenteric vein thrombosis, death, sudden death, sepsis, renal failure, and aortic dissection.

There were 7 deaths in the ruxolitinib arm as well. The causes of death were melena, sepsis, pneumonia, head injury, acute myeloid leukemia, recurrent mantle cell lymphoma, and coma.

Transformation to acute myeloid leukemia occurred in 1 patient in the momelotinib arm (grade 4) and 2 patients in the ruxolitinib arm (grade 3 and grade 5).

of Medical Research

Carbohydrates on the surface of malaria parasites play a critical role in the parasites’ ability to infect mosquito and human hosts, according to research published in Nature Communications.

Researchers found that Plasmodium falciparum “tags” its proteins with carbohydrates in order to stabilize and transport them.

And this process is crucial to completing the parasite’s life cycle.

“Malaria parasites have a complex life cycle that involves constant shape-shifting to evade detection and infect humans and, subsequently, mosquitoes,” said study author Justin Boddey, PhD, of The Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia.

“We found that the parasite’s ability to ‘tag’ key proteins with carbohydrates is important for 2 stages of the malaria life cycle. It is critical for the earliest stages of human infection, when the parasite migrates through the body and invades in the liver, and later, when it is transmitted back to the mosquito from an infected human, enabling the parasite to be spread between people.”

“Interfering with the parasite’s ability to attach these carbohydrates to its proteins hinders liver infection and transmission to the mosquito and weakens the parasite to the point that it cannot survive in the host.”

Dr Boddey and his colleagues said this research suggests steps that may improve the efficacy of the malaria vaccine RTS,S/AS01 (Mosquirix).

“The protein used in the RTS,S vaccine mimics one of the proteins we’ve been studying on the surface of the malaria parasite that is readily recognized by the immune system,” said study author Ethan D. Goddard-Borger, PhD, of The Walter and Eliza Hall Institute of Medical Research.

“It was hoped that the vaccine would generate a good antibody response that protected against the parasite. However, it has, unfortunately, not been as effective at evoking protective immunity as hoped.”

“With this study, we’ve shown that the parasite protein is tagged with carbohydrates, making it slightly different to the vaccine, so the antibodies produced may not be optimal for recognizing target parasites.”

Dr Goddard-Borger said there were many documented cases where attaching carbohydrates to a protein improved its efficacy as a vaccine.

“It may be that a version of RTS,S with added carbohydrates will perform better than the current vaccine,” he said. “Now that we know how important these carbohydrates are to the parasite, we can be confident that the malaria parasite cannot ‘escape’ vaccination pressure by doing away with its carbohydrates.”

of Medical Research

Carbohydrates on the surface of malaria parasites play a critical role in the parasites’ ability to infect mosquito and human hosts, according to research published in Nature Communications.

Researchers found that Plasmodium falciparum “tags” its proteins with carbohydrates in order to stabilize and transport them.

And this process is crucial to completing the parasite’s life cycle.

“Malaria parasites have a complex life cycle that involves constant shape-shifting to evade detection and infect humans and, subsequently, mosquitoes,” said study author Justin Boddey, PhD, of The Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia.

“We found that the parasite’s ability to ‘tag’ key proteins with carbohydrates is important for 2 stages of the malaria life cycle. It is critical for the earliest stages of human infection, when the parasite migrates through the body and invades in the liver, and later, when it is transmitted back to the mosquito from an infected human, enabling the parasite to be spread between people.”

“Interfering with the parasite’s ability to attach these carbohydrates to its proteins hinders liver infection and transmission to the mosquito and weakens the parasite to the point that it cannot survive in the host.”

Dr Boddey and his colleagues said this research suggests steps that may improve the efficacy of the malaria vaccine RTS,S/AS01 (Mosquirix).

“The protein used in the RTS,S vaccine mimics one of the proteins we’ve been studying on the surface of the malaria parasite that is readily recognized by the immune system,” said study author Ethan D. Goddard-Borger, PhD, of The Walter and Eliza Hall Institute of Medical Research.

“It was hoped that the vaccine would generate a good antibody response that protected against the parasite. However, it has, unfortunately, not been as effective at evoking protective immunity as hoped.”

“With this study, we’ve shown that the parasite protein is tagged with carbohydrates, making it slightly different to the vaccine, so the antibodies produced may not be optimal for recognizing target parasites.”

Dr Goddard-Borger said there were many documented cases where attaching carbohydrates to a protein improved its efficacy as a vaccine.

“It may be that a version of RTS,S with added carbohydrates will perform better than the current vaccine,” he said. “Now that we know how important these carbohydrates are to the parasite, we can be confident that the malaria parasite cannot ‘escape’ vaccination pressure by doing away with its carbohydrates.”

of Medical Research

Carbohydrates on the surface of malaria parasites play a critical role in the parasites’ ability to infect mosquito and human hosts, according to research published in Nature Communications.

Researchers found that Plasmodium falciparum “tags” its proteins with carbohydrates in order to stabilize and transport them.

And this process is crucial to completing the parasite’s life cycle.

“Malaria parasites have a complex life cycle that involves constant shape-shifting to evade detection and infect humans and, subsequently, mosquitoes,” said study author Justin Boddey, PhD, of The Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia.

“We found that the parasite’s ability to ‘tag’ key proteins with carbohydrates is important for 2 stages of the malaria life cycle. It is critical for the earliest stages of human infection, when the parasite migrates through the body and invades in the liver, and later, when it is transmitted back to the mosquito from an infected human, enabling the parasite to be spread between people.”

“Interfering with the parasite’s ability to attach these carbohydrates to its proteins hinders liver infection and transmission to the mosquito and weakens the parasite to the point that it cannot survive in the host.”

Dr Boddey and his colleagues said this research suggests steps that may improve the efficacy of the malaria vaccine RTS,S/AS01 (Mosquirix).

“The protein used in the RTS,S vaccine mimics one of the proteins we’ve been studying on the surface of the malaria parasite that is readily recognized by the immune system,” said study author Ethan D. Goddard-Borger, PhD, of The Walter and Eliza Hall Institute of Medical Research.

“It was hoped that the vaccine would generate a good antibody response that protected against the parasite. However, it has, unfortunately, not been as effective at evoking protective immunity as hoped.”

“With this study, we’ve shown that the parasite protein is tagged with carbohydrates, making it slightly different to the vaccine, so the antibodies produced may not be optimal for recognizing target parasites.”

Dr Goddard-Borger said there were many documented cases where attaching carbohydrates to a protein improved its efficacy as a vaccine.

“It may be that a version of RTS,S with added carbohydrates will perform better than the current vaccine,” he said. “Now that we know how important these carbohydrates are to the parasite, we can be confident that the malaria parasite cannot ‘escape’ vaccination pressure by doing away with its carbohydrates.”