Andrew D. Bowser

SAN DIEGO – Prophylaxis with rivaroxaban significantly reduced the rate of venous thromboembolism and associated death in high-risk ambulatory cancer patients receiving systemic therapy, results of a randomized trial show.

The reduction in venous thromboembolism (VTE) or VTE-related death was not statistically significant in the primary analysis, in part because a large proportion of patients stopped taking the direct oral anticoagulant, according to investigator Alok A. Khorana, MD, of the Cleveland Clinic.

However, the reduction in events was significant in a prespecified secondary analysis limited to the on-treatment period, Dr. Khorana reported at the annual meeting of the American Society of Hematology, adding that rates of major and nonmajor bleeding were low.

Results are “eagerly awaited” from a different prophylaxis trial – the AVERT study – looking at another direct oral anticoagulant in high-risk cancer patients, Dr. Khorana said in a late-breaking abstracts session.

“If the findings of that trial are consistent with ours, then we certainly hope that these findings should inform future recommendations regarding thromboprophylaxis for high-risk ambulatory cancer patients, and then the landscape of anticoagulation in the cancer population should start to shift from management of events to primary prevention,” he said.

In the study by Dr. Khorana and his colleagues, known as CASSINI, 841 patients with various solid tumors and lymphomas were randomized to either rivaroxaban 10 mg or placebo once daily. The patients, enrolled at 143 study centers in 11 countries, all had a Khorana risk score of 2 or greater.

In the primary analysis period of 180 days, the composite endpoint of VTE or VTE-related death occurred in 5.95% of the rivaroxaban-treated group and 8.79% of the placebo group (hazard ratio, 0.66; 95% confidence interval, 0.40-1.09; P = .101). However, a total of 177 patients (43.7%) stopped rivaroxaban earlier than 180 days, and likewise, 203 patients (50.2%) stopped placebo early.

In a prespecified secondary analysis looking just at the period of time when patients were actually taking rivaroxaban or placebo, rivaroxaban did significantly reduce risk of VTE or VTE-related death, Dr. Khorana said. The composite endpoint occurred in 2.62% of the rivaroxaban patients and 6.41% of placebo patients in that on-treatment analysis (HR, 0.40; 95% CI, 0.20-0.80; P = .007).

Rates of major bleeding and clinically relevant nonmajor bleeding were not significantly different between groups, according to results of a safety analysis. Major bleeding occurred in eight rivaroxaban patients and four placebo patients, or 1.98% and 0.99%, respectively (P = .265).

CASSINI was sponsored by Bayer and Janssen. Dr. Khorana reported disclosures related to Janssen, Bayer, PAREXEL, Sanofi, Pfizer, TriSalus Life Sciences, Halozyme, Seattle Genetics, AngioDynamics, and others.

SAN DIEGO – Prophylaxis with rivaroxaban significantly reduced the rate of venous thromboembolism and associated death in high-risk ambulatory cancer patients receiving systemic therapy, results of a randomized trial show.

The reduction in venous thromboembolism (VTE) or VTE-related death was not statistically significant in the primary analysis, in part because a large proportion of patients stopped taking the direct oral anticoagulant, according to investigator Alok A. Khorana, MD, of the Cleveland Clinic.

However, the reduction in events was significant in a prespecified secondary analysis limited to the on-treatment period, Dr. Khorana reported at the annual meeting of the American Society of Hematology, adding that rates of major and nonmajor bleeding were low.

Results are “eagerly awaited” from a different prophylaxis trial – the AVERT study – looking at another direct oral anticoagulant in high-risk cancer patients, Dr. Khorana said in a late-breaking abstracts session.

“If the findings of that trial are consistent with ours, then we certainly hope that these findings should inform future recommendations regarding thromboprophylaxis for high-risk ambulatory cancer patients, and then the landscape of anticoagulation in the cancer population should start to shift from management of events to primary prevention,” he said.

In the study by Dr. Khorana and his colleagues, known as CASSINI, 841 patients with various solid tumors and lymphomas were randomized to either rivaroxaban 10 mg or placebo once daily. The patients, enrolled at 143 study centers in 11 countries, all had a Khorana risk score of 2 or greater.

In the primary analysis period of 180 days, the composite endpoint of VTE or VTE-related death occurred in 5.95% of the rivaroxaban-treated group and 8.79% of the placebo group (hazard ratio, 0.66; 95% confidence interval, 0.40-1.09; P = .101). However, a total of 177 patients (43.7%) stopped rivaroxaban earlier than 180 days, and likewise, 203 patients (50.2%) stopped placebo early.

In a prespecified secondary analysis looking just at the period of time when patients were actually taking rivaroxaban or placebo, rivaroxaban did significantly reduce risk of VTE or VTE-related death, Dr. Khorana said. The composite endpoint occurred in 2.62% of the rivaroxaban patients and 6.41% of placebo patients in that on-treatment analysis (HR, 0.40; 95% CI, 0.20-0.80; P = .007).

Rates of major bleeding and clinically relevant nonmajor bleeding were not significantly different between groups, according to results of a safety analysis. Major bleeding occurred in eight rivaroxaban patients and four placebo patients, or 1.98% and 0.99%, respectively (P = .265).

CASSINI was sponsored by Bayer and Janssen. Dr. Khorana reported disclosures related to Janssen, Bayer, PAREXEL, Sanofi, Pfizer, TriSalus Life Sciences, Halozyme, Seattle Genetics, AngioDynamics, and others.

SAN DIEGO – Prophylaxis with rivaroxaban significantly reduced the rate of venous thromboembolism and associated death in high-risk ambulatory cancer patients receiving systemic therapy, results of a randomized trial show.

The reduction in venous thromboembolism (VTE) or VTE-related death was not statistically significant in the primary analysis, in part because a large proportion of patients stopped taking the direct oral anticoagulant, according to investigator Alok A. Khorana, MD, of the Cleveland Clinic.

However, the reduction in events was significant in a prespecified secondary analysis limited to the on-treatment period, Dr. Khorana reported at the annual meeting of the American Society of Hematology, adding that rates of major and nonmajor bleeding were low.

Results are “eagerly awaited” from a different prophylaxis trial – the AVERT study – looking at another direct oral anticoagulant in high-risk cancer patients, Dr. Khorana said in a late-breaking abstracts session.

“If the findings of that trial are consistent with ours, then we certainly hope that these findings should inform future recommendations regarding thromboprophylaxis for high-risk ambulatory cancer patients, and then the landscape of anticoagulation in the cancer population should start to shift from management of events to primary prevention,” he said.

In the study by Dr. Khorana and his colleagues, known as CASSINI, 841 patients with various solid tumors and lymphomas were randomized to either rivaroxaban 10 mg or placebo once daily. The patients, enrolled at 143 study centers in 11 countries, all had a Khorana risk score of 2 or greater.

In the primary analysis period of 180 days, the composite endpoint of VTE or VTE-related death occurred in 5.95% of the rivaroxaban-treated group and 8.79% of the placebo group (hazard ratio, 0.66; 95% confidence interval, 0.40-1.09; P = .101). However, a total of 177 patients (43.7%) stopped rivaroxaban earlier than 180 days, and likewise, 203 patients (50.2%) stopped placebo early.

In a prespecified secondary analysis looking just at the period of time when patients were actually taking rivaroxaban or placebo, rivaroxaban did significantly reduce risk of VTE or VTE-related death, Dr. Khorana said. The composite endpoint occurred in 2.62% of the rivaroxaban patients and 6.41% of placebo patients in that on-treatment analysis (HR, 0.40; 95% CI, 0.20-0.80; P = .007).

Rates of major bleeding and clinically relevant nonmajor bleeding were not significantly different between groups, according to results of a safety analysis. Major bleeding occurred in eight rivaroxaban patients and four placebo patients, or 1.98% and 0.99%, respectively (P = .265).

CASSINI was sponsored by Bayer and Janssen. Dr. Khorana reported disclosures related to Janssen, Bayer, PAREXEL, Sanofi, Pfizer, TriSalus Life Sciences, Halozyme, Seattle Genetics, AngioDynamics, and others.

Photo courtesy of ASH

SAN DIEGO—Daily hydroxyurea (HU) treatment is feasible, safe, and effective for children with sickle cell disease (SCD) in sub-Saharan Africa, according to a phase 1/2 trial.

During HU treatment, children experienced less vaso-occlusive pain, fewer cases of malaria and other infections, and lower rates of transfusions and death, compared to rates observed in the pretreatment screening phase of the trial.

“Based on that data, we believe that wider access to hydroxyurea for sickle cell anemia has the potential to save millions of lives in Africa,” said Léon Tshilolo, MD, PhD, of Centre Hospitalier Monkole in Kinshasa, Democratic Republic of the Congo.

Dr. Tshilolo reported the data, from the REACH trial (NCT01966731), during the plenary session at the 2018 ASH Annual Meeting (abstract 3*). Data were simultaneously published in The New England Journal of Medicine.

Use of HU has been limited in Africa because of cost, access issues, and challenges associated with laboratory monitoring, according to researchers.

Moreover, most of the efficacy data on HU come from studies conducted in the United States, Europe, and other high-income settings, said senior study author Russell E. Ware, MD, PhD, of Cincinnati Children’s Hospital Center in Ohio.

“Now that there’s data in an African setting, I think this will go a long way to advancing [HU therapy] and encouraging governments, organizations, and pharmaceutical companies to bring it in,” Dr. Ware said.

To collect the data, Drs. Ware and Tshilolo and their colleagues evaluated SCD patients, ages 1 to 10, living in four sub-Saharan African countries—Angola, Democratic Republic of the Congo, Kenya, and Uganda.

The children completed a 2-month pretreatment screening phase designed to capture baseline clinical and laboratory data.

The children were started at 15 mg/kg to 20 mg/kg of HU for 6 months, followed by escalation to the maximum-tolerated dose.

A total of 606 children were treated, 600 of them for 3 months. Treatment is ongoing, but the mean treatment duration at the time of analysis was 29 months.

Results

The average maximum tolerated dose was 22.5 mg/kg/day. Dose-limiting toxicities occurred in 5.1% of the children, which was below the 20% protocol-specified threshold for safety, Dr. Tshilolo said.

Dose-limiting toxicities included severe anemia, reticulocytopenia, neutropenia, and thrombocytopenia. However, there were similar rates of these events during the screening period and the treatment period.

The rate of vaso-occlusive pain during HU treatment was 44.6 events per 100 patient-years, compared with 98.3 events per 100 patient-years in the pretreatment period (incidence rate ratio [IRR], 0.45; 95% confidence interval [CI], 0.37-0.56).

The rate of malaria infection was 22.9 events per 100 patient-years in the HU treatment period, compared to 46.9 events in the pretreatment period (IRR, 0.49; 95% CI, 0.37-0.66).

The rate of nonmalaria infections was 90.0 events per 100 patient-years in the HU treatment period, compared to 142.5 events per 100 patient-years in the pretreatment period (IRR, 0.62; 95% CI, 0.53-0.72).

Dr. Tshilolo said the researchers were “encouraged” by the reduced infection rates, particularly in light of previous concerns that HU could suppress the immune system and put children at risk for malaria.

The rate of transfusion during HU treatment was 14.2 events per 100 patient-years, compared to 43.3 events per 100 patient-years (IRR, 0.33; 95% CI, 0.23 to 0.47).

Death rates were 1.1 per 100 patient-years in the HU treatment period and 3.6 per 100 patient-years in the pretreatment period (IRR, 0.30; 95% CI, 0.10-0.88).

Dr. Tshilolo reported grants from the National Institutes of Health/National Heart, Lung, and Blood Institute and Cincinnati Children’s Research Foundation, along with nonfinancial support from Bristol-Myers Squibb. Dr. Ware reported grants from the National Institutes of Health/National Heart, Lung, and Blood Institute and Bristol-Myers Squibb.

*Data in the abstract differ from the presentation and the article.

Photo courtesy of ASH

SAN DIEGO—Daily hydroxyurea (HU) treatment is feasible, safe, and effective for children with sickle cell disease (SCD) in sub-Saharan Africa, according to a phase 1/2 trial.

During HU treatment, children experienced less vaso-occlusive pain, fewer cases of malaria and other infections, and lower rates of transfusions and death, compared to rates observed in the pretreatment screening phase of the trial.

“Based on that data, we believe that wider access to hydroxyurea for sickle cell anemia has the potential to save millions of lives in Africa,” said Léon Tshilolo, MD, PhD, of Centre Hospitalier Monkole in Kinshasa, Democratic Republic of the Congo.

Dr. Tshilolo reported the data, from the REACH trial (NCT01966731), during the plenary session at the 2018 ASH Annual Meeting (abstract 3*). Data were simultaneously published in The New England Journal of Medicine.

Use of HU has been limited in Africa because of cost, access issues, and challenges associated with laboratory monitoring, according to researchers.

Moreover, most of the efficacy data on HU come from studies conducted in the United States, Europe, and other high-income settings, said senior study author Russell E. Ware, MD, PhD, of Cincinnati Children’s Hospital Center in Ohio.

“Now that there’s data in an African setting, I think this will go a long way to advancing [HU therapy] and encouraging governments, organizations, and pharmaceutical companies to bring it in,” Dr. Ware said.

To collect the data, Drs. Ware and Tshilolo and their colleagues evaluated SCD patients, ages 1 to 10, living in four sub-Saharan African countries—Angola, Democratic Republic of the Congo, Kenya, and Uganda.

The children completed a 2-month pretreatment screening phase designed to capture baseline clinical and laboratory data.

The children were started at 15 mg/kg to 20 mg/kg of HU for 6 months, followed by escalation to the maximum-tolerated dose.

A total of 606 children were treated, 600 of them for 3 months. Treatment is ongoing, but the mean treatment duration at the time of analysis was 29 months.

Results

The average maximum tolerated dose was 22.5 mg/kg/day. Dose-limiting toxicities occurred in 5.1% of the children, which was below the 20% protocol-specified threshold for safety, Dr. Tshilolo said.

Dose-limiting toxicities included severe anemia, reticulocytopenia, neutropenia, and thrombocytopenia. However, there were similar rates of these events during the screening period and the treatment period.

The rate of vaso-occlusive pain during HU treatment was 44.6 events per 100 patient-years, compared with 98.3 events per 100 patient-years in the pretreatment period (incidence rate ratio [IRR], 0.45; 95% confidence interval [CI], 0.37-0.56).

The rate of malaria infection was 22.9 events per 100 patient-years in the HU treatment period, compared to 46.9 events in the pretreatment period (IRR, 0.49; 95% CI, 0.37-0.66).

The rate of nonmalaria infections was 90.0 events per 100 patient-years in the HU treatment period, compared to 142.5 events per 100 patient-years in the pretreatment period (IRR, 0.62; 95% CI, 0.53-0.72).

Dr. Tshilolo said the researchers were “encouraged” by the reduced infection rates, particularly in light of previous concerns that HU could suppress the immune system and put children at risk for malaria.

The rate of transfusion during HU treatment was 14.2 events per 100 patient-years, compared to 43.3 events per 100 patient-years (IRR, 0.33; 95% CI, 0.23 to 0.47).

Death rates were 1.1 per 100 patient-years in the HU treatment period and 3.6 per 100 patient-years in the pretreatment period (IRR, 0.30; 95% CI, 0.10-0.88).

Dr. Tshilolo reported grants from the National Institutes of Health/National Heart, Lung, and Blood Institute and Cincinnati Children’s Research Foundation, along with nonfinancial support from Bristol-Myers Squibb. Dr. Ware reported grants from the National Institutes of Health/National Heart, Lung, and Blood Institute and Bristol-Myers Squibb.

*Data in the abstract differ from the presentation and the article.

Photo courtesy of ASH

SAN DIEGO—Daily hydroxyurea (HU) treatment is feasible, safe, and effective for children with sickle cell disease (SCD) in sub-Saharan Africa, according to a phase 1/2 trial.

During HU treatment, children experienced less vaso-occlusive pain, fewer cases of malaria and other infections, and lower rates of transfusions and death, compared to rates observed in the pretreatment screening phase of the trial.

“Based on that data, we believe that wider access to hydroxyurea for sickle cell anemia has the potential to save millions of lives in Africa,” said Léon Tshilolo, MD, PhD, of Centre Hospitalier Monkole in Kinshasa, Democratic Republic of the Congo.

Dr. Tshilolo reported the data, from the REACH trial (NCT01966731), during the plenary session at the 2018 ASH Annual Meeting (abstract 3*). Data were simultaneously published in The New England Journal of Medicine.

Use of HU has been limited in Africa because of cost, access issues, and challenges associated with laboratory monitoring, according to researchers.

Moreover, most of the efficacy data on HU come from studies conducted in the United States, Europe, and other high-income settings, said senior study author Russell E. Ware, MD, PhD, of Cincinnati Children’s Hospital Center in Ohio.

“Now that there’s data in an African setting, I think this will go a long way to advancing [HU therapy] and encouraging governments, organizations, and pharmaceutical companies to bring it in,” Dr. Ware said.

To collect the data, Drs. Ware and Tshilolo and their colleagues evaluated SCD patients, ages 1 to 10, living in four sub-Saharan African countries—Angola, Democratic Republic of the Congo, Kenya, and Uganda.

The children completed a 2-month pretreatment screening phase designed to capture baseline clinical and laboratory data.

The children were started at 15 mg/kg to 20 mg/kg of HU for 6 months, followed by escalation to the maximum-tolerated dose.

A total of 606 children were treated, 600 of them for 3 months. Treatment is ongoing, but the mean treatment duration at the time of analysis was 29 months.

Results

The average maximum tolerated dose was 22.5 mg/kg/day. Dose-limiting toxicities occurred in 5.1% of the children, which was below the 20% protocol-specified threshold for safety, Dr. Tshilolo said.

Dose-limiting toxicities included severe anemia, reticulocytopenia, neutropenia, and thrombocytopenia. However, there were similar rates of these events during the screening period and the treatment period.

The rate of vaso-occlusive pain during HU treatment was 44.6 events per 100 patient-years, compared with 98.3 events per 100 patient-years in the pretreatment period (incidence rate ratio [IRR], 0.45; 95% confidence interval [CI], 0.37-0.56).

The rate of malaria infection was 22.9 events per 100 patient-years in the HU treatment period, compared to 46.9 events in the pretreatment period (IRR, 0.49; 95% CI, 0.37-0.66).

The rate of nonmalaria infections was 90.0 events per 100 patient-years in the HU treatment period, compared to 142.5 events per 100 patient-years in the pretreatment period (IRR, 0.62; 95% CI, 0.53-0.72).

Dr. Tshilolo said the researchers were “encouraged” by the reduced infection rates, particularly in light of previous concerns that HU could suppress the immune system and put children at risk for malaria.

The rate of transfusion during HU treatment was 14.2 events per 100 patient-years, compared to 43.3 events per 100 patient-years (IRR, 0.33; 95% CI, 0.23 to 0.47).

Death rates were 1.1 per 100 patient-years in the HU treatment period and 3.6 per 100 patient-years in the pretreatment period (IRR, 0.30; 95% CI, 0.10-0.88).

Dr. Tshilolo reported grants from the National Institutes of Health/National Heart, Lung, and Blood Institute and Cincinnati Children’s Research Foundation, along with nonfinancial support from Bristol-Myers Squibb. Dr. Ware reported grants from the National Institutes of Health/National Heart, Lung, and Blood Institute and Bristol-Myers Squibb.

*Data in the abstract differ from the presentation and the article.

San Diego – In patients with atrial fibrillation who had direct oral anticoagulant (DOAC) interruption for an elective surgery, a simple and standardized management strategy yielded low rates of bleeding and thromboembolism, according to results of a prospective study of more than 3,000 patients.

Rates of major bleeding were less than 2% and rates of arterial thromboembolism were less than 1% in patients managed in accordance with the strategy, which foregoes heparin bridging and preoperative coagulation testing, according to investigator James D. Douketis, MD, of St. Joseph’s Healthcare and McMaster University, Hamilton, Ont.

“This is the first study to demonstrate the safety of a standardized perioperative management approach in a patients with atrial fibrillation who are taking a DOAC, and we hope will establish a standard and will have an effect on our clinical practice guidelines,” Dr. Douketis said during a press briefing at the annual meeting of the American Society of Hematology.

This trial offers the “most definitive evidence to date” that atrial fibrillation patients can – in an organized fashion based on bleeding risk – safely stop taking DOACs, said Mark Crowther, MD, chair and professor of medicine at McMaster University.

“This study will almost instantaneously establish a treatment practice and a treatment standard for the vast number of patients in North America and around the world who take these drugs,” added Dr. Crowther, who moderated the press briefing.

The PAUSE study included three parallel cohorts of atrial fibrillation patients taking DOACs (apixaban, dabigatran, or rivaroxaban) who required anticoagulant interruption for an elective surgery or procedure.

The DOAC interruptions were done using standardized protocols based on the pharmacokinetic properties of each DOAC, procedure-associated bleeding risk, and creatinine clearance, the investigators reported.

The interruptions occurred 1 day before and after low bleeding risk surgeries, and 2 days before and after high bleeding risk surgeries, while longer interruptions were used in patients receiving dabigatran who had a creatinine clearance below 50 mL/min.

A total of 3,007 patients at 23 sites in Canada, the United States, and Europe were managed by this approach in the PAUSE study – 1,257 patients receiving apixaban, 668 receiving dabigatran, and 1,082 receiving rivaroxaban – and were evaluated weekly for 30 days post-procedure.

PAUSE is the largest study to date that addresses how to manage the common problem of perioperative DOAC management. It is likely to have a practice-changing impact and will inform future practice guidelines in perioperative care.

The 30-day postoperative rate of major bleeding was low, according to investigators, at 1.35% (95% confidence interval, 0-2.00%) for apixaban, 0.90% (95% CI, 0-1.73%) for dabigatran, and 1.85% (95% CI, 0-2.65%) for rivaroxaban, Dr. Douketis reported.

Likewise, the rate of arterial thromboembolism was low at 0.16% (95% CI, 0-0.48%) for apixaban, 0.6% (95% CI, 0-1.33%) for dabigatran, and 0.37% (95% CI, 0-0.82%) for rivaroxaban, he said.

Most patients (greater than 90%) had minimal to no residual DOAC levels at the time of surgery, the investigator added.

The study was funded by the Canadian Institutes of Health Research and the H&S Foundation of Canada. Dr. Douketis reported disclosures related to Janssen, which makes rivaroxaban; Boehringer-Ingelheim, which makes dabigatran; and other companies. Dr. Crowther reported financial relationships with Bristol-Myers Squibb and other companies.

SOURCE: Douketis J et al. ASH 2018, Abstract LBA-5.

San Diego – In patients with atrial fibrillation who had direct oral anticoagulant (DOAC) interruption for an elective surgery, a simple and standardized management strategy yielded low rates of bleeding and thromboembolism, according to results of a prospective study of more than 3,000 patients.

Rates of major bleeding were less than 2% and rates of arterial thromboembolism were less than 1% in patients managed in accordance with the strategy, which foregoes heparin bridging and preoperative coagulation testing, according to investigator James D. Douketis, MD, of St. Joseph’s Healthcare and McMaster University, Hamilton, Ont.

“This is the first study to demonstrate the safety of a standardized perioperative management approach in a patients with atrial fibrillation who are taking a DOAC, and we hope will establish a standard and will have an effect on our clinical practice guidelines,” Dr. Douketis said during a press briefing at the annual meeting of the American Society of Hematology.

This trial offers the “most definitive evidence to date” that atrial fibrillation patients can – in an organized fashion based on bleeding risk – safely stop taking DOACs, said Mark Crowther, MD, chair and professor of medicine at McMaster University.

“This study will almost instantaneously establish a treatment practice and a treatment standard for the vast number of patients in North America and around the world who take these drugs,” added Dr. Crowther, who moderated the press briefing.

The PAUSE study included three parallel cohorts of atrial fibrillation patients taking DOACs (apixaban, dabigatran, or rivaroxaban) who required anticoagulant interruption for an elective surgery or procedure.

The DOAC interruptions were done using standardized protocols based on the pharmacokinetic properties of each DOAC, procedure-associated bleeding risk, and creatinine clearance, the investigators reported.

The interruptions occurred 1 day before and after low bleeding risk surgeries, and 2 days before and after high bleeding risk surgeries, while longer interruptions were used in patients receiving dabigatran who had a creatinine clearance below 50 mL/min.

A total of 3,007 patients at 23 sites in Canada, the United States, and Europe were managed by this approach in the PAUSE study – 1,257 patients receiving apixaban, 668 receiving dabigatran, and 1,082 receiving rivaroxaban – and were evaluated weekly for 30 days post-procedure.

PAUSE is the largest study to date that addresses how to manage the common problem of perioperative DOAC management. It is likely to have a practice-changing impact and will inform future practice guidelines in perioperative care.

The 30-day postoperative rate of major bleeding was low, according to investigators, at 1.35% (95% confidence interval, 0-2.00%) for apixaban, 0.90% (95% CI, 0-1.73%) for dabigatran, and 1.85% (95% CI, 0-2.65%) for rivaroxaban, Dr. Douketis reported.

Likewise, the rate of arterial thromboembolism was low at 0.16% (95% CI, 0-0.48%) for apixaban, 0.6% (95% CI, 0-1.33%) for dabigatran, and 0.37% (95% CI, 0-0.82%) for rivaroxaban, he said.

Most patients (greater than 90%) had minimal to no residual DOAC levels at the time of surgery, the investigator added.

The study was funded by the Canadian Institutes of Health Research and the H&S Foundation of Canada. Dr. Douketis reported disclosures related to Janssen, which makes rivaroxaban; Boehringer-Ingelheim, which makes dabigatran; and other companies. Dr. Crowther reported financial relationships with Bristol-Myers Squibb and other companies.

SOURCE: Douketis J et al. ASH 2018, Abstract LBA-5.

San Diego – In patients with atrial fibrillation who had direct oral anticoagulant (DOAC) interruption for an elective surgery, a simple and standardized management strategy yielded low rates of bleeding and thromboembolism, according to results of a prospective study of more than 3,000 patients.

Rates of major bleeding were less than 2% and rates of arterial thromboembolism were less than 1% in patients managed in accordance with the strategy, which foregoes heparin bridging and preoperative coagulation testing, according to investigator James D. Douketis, MD, of St. Joseph’s Healthcare and McMaster University, Hamilton, Ont.

“This is the first study to demonstrate the safety of a standardized perioperative management approach in a patients with atrial fibrillation who are taking a DOAC, and we hope will establish a standard and will have an effect on our clinical practice guidelines,” Dr. Douketis said during a press briefing at the annual meeting of the American Society of Hematology.

This trial offers the “most definitive evidence to date” that atrial fibrillation patients can – in an organized fashion based on bleeding risk – safely stop taking DOACs, said Mark Crowther, MD, chair and professor of medicine at McMaster University.

“This study will almost instantaneously establish a treatment practice and a treatment standard for the vast number of patients in North America and around the world who take these drugs,” added Dr. Crowther, who moderated the press briefing.

The PAUSE study included three parallel cohorts of atrial fibrillation patients taking DOACs (apixaban, dabigatran, or rivaroxaban) who required anticoagulant interruption for an elective surgery or procedure.

The DOAC interruptions were done using standardized protocols based on the pharmacokinetic properties of each DOAC, procedure-associated bleeding risk, and creatinine clearance, the investigators reported.

The interruptions occurred 1 day before and after low bleeding risk surgeries, and 2 days before and after high bleeding risk surgeries, while longer interruptions were used in patients receiving dabigatran who had a creatinine clearance below 50 mL/min.

A total of 3,007 patients at 23 sites in Canada, the United States, and Europe were managed by this approach in the PAUSE study – 1,257 patients receiving apixaban, 668 receiving dabigatran, and 1,082 receiving rivaroxaban – and were evaluated weekly for 30 days post-procedure.

PAUSE is the largest study to date that addresses how to manage the common problem of perioperative DOAC management. It is likely to have a practice-changing impact and will inform future practice guidelines in perioperative care.

The 30-day postoperative rate of major bleeding was low, according to investigators, at 1.35% (95% confidence interval, 0-2.00%) for apixaban, 0.90% (95% CI, 0-1.73%) for dabigatran, and 1.85% (95% CI, 0-2.65%) for rivaroxaban, Dr. Douketis reported.

Likewise, the rate of arterial thromboembolism was low at 0.16% (95% CI, 0-0.48%) for apixaban, 0.6% (95% CI, 0-1.33%) for dabigatran, and 0.37% (95% CI, 0-0.82%) for rivaroxaban, he said.

Most patients (greater than 90%) had minimal to no residual DOAC levels at the time of surgery, the investigator added.

The study was funded by the Canadian Institutes of Health Research and the H&S Foundation of Canada. Dr. Douketis reported disclosures related to Janssen, which makes rivaroxaban; Boehringer-Ingelheim, which makes dabigatran; and other companies. Dr. Crowther reported financial relationships with Bristol-Myers Squibb and other companies.

SOURCE: Douketis J et al. ASH 2018, Abstract LBA-5.

PHOENIX – An initiative designed to reduce avoidable emergency room visits and hospitalizations cut admissions by 16%, according to a report from a large, independent, community-based oncology practice.

The program saved nearly $3.2 million in Medicare costs over the course of the year, said Molly Mendenhall, RN, of Oncology Hematology Care in Cincinnati.

“By keeping those patients out of the hospital, we were able to improve patient quality of life, and increase patient satisfaction by treating them in their home clinic instead of the hospital,” Ms. Mendenhall said at a symposium on quality care sponsored by the American Society of Clinical Oncology.

The campaign was developed in anticipation of participating in the Oncology Care Model (OCM), a program focused on providing coordinated and high-quality care for Medicare oncology patients at the same or lower cost.

Prior to participating in OCM, Ms. Mendenhall and her colleagues set up an after-hours phone triage system, proactive chemotherapy follow-up calls, and a Saturday-Sunday urgent care clinic designed to help avoid any unnecessary hospitalizations over the weekend.

They also set up a 2-hour structured OCM treatment planning visit to prioritize shared decision making between the patient and the clinical team regarding diagnosis, symptom management, financial assistance, and other aspects of care.

The most influential part of the initiative, according to Ms. Mendenhall, was a patient-directed “Call Us Early – Call Us First” campaign that included symptom management teaching sheets, a 34-page teaching book, and branded buttons, pens, and magnets all designed to emphasize the patient responsibility to use the phone.

“All of those previous steps really wouldn’t make a difference if the patients still weren’t calling us,” Ms. Mendenhall explained.

Over the first year of participation in the OCM program, the oncology practice saw a 16% statistically significant reduction in hospital admissions (P = .005). The number of inpatient admissions per 100 patients dropped from 26.8 at baseline to 22.6 at the most recent follow-up in a report published simultaneously in the Journal of Oncology Practice.

Reduced admissions translated into a drop of $798,000 in inpatient costs per quarter over 1,600 patients, or $3.129 million in savings for the Centers for Medicare & Medicaid Services over the first year of participation in OCM, according to the researchers.

Patient satisfaction scores trended positively over the course of that year based on a review of blinded surveys that asked patients to rate clinical care, communication, access, information exchange, and other aspects of their experience.

Scores on those surveys were 8.03 on a scale of 0-10 (low to high) during the baseline period of January to September 2016, the researchers said. Scores were 8.29 and 8.26 for two follow-up surveys.

Ms. Mendenhall had no disclosures to report. Coauthors on the study provided disclosures related to Janssen Oncology, Pfizer, Amgen, Abbvie, Merck, Pharmacyclics, Bristol-Myers Squibb, Celgene, Genentech/Roche, AZTherapies, and Lilly. Two coauthors reported leadership, stock, or other ownership interests in Oncology Hematology Care/US Oncology.

SOURCE: Mendenhall M et al. Quality Care Symposium, Abstract 30.

PHOENIX – An initiative designed to reduce avoidable emergency room visits and hospitalizations cut admissions by 16%, according to a report from a large, independent, community-based oncology practice.

The program saved nearly $3.2 million in Medicare costs over the course of the year, said Molly Mendenhall, RN, of Oncology Hematology Care in Cincinnati.

“By keeping those patients out of the hospital, we were able to improve patient quality of life, and increase patient satisfaction by treating them in their home clinic instead of the hospital,” Ms. Mendenhall said at a symposium on quality care sponsored by the American Society of Clinical Oncology.

The campaign was developed in anticipation of participating in the Oncology Care Model (OCM), a program focused on providing coordinated and high-quality care for Medicare oncology patients at the same or lower cost.

Prior to participating in OCM, Ms. Mendenhall and her colleagues set up an after-hours phone triage system, proactive chemotherapy follow-up calls, and a Saturday-Sunday urgent care clinic designed to help avoid any unnecessary hospitalizations over the weekend.

They also set up a 2-hour structured OCM treatment planning visit to prioritize shared decision making between the patient and the clinical team regarding diagnosis, symptom management, financial assistance, and other aspects of care.

The most influential part of the initiative, according to Ms. Mendenhall, was a patient-directed “Call Us Early – Call Us First” campaign that included symptom management teaching sheets, a 34-page teaching book, and branded buttons, pens, and magnets all designed to emphasize the patient responsibility to use the phone.

“All of those previous steps really wouldn’t make a difference if the patients still weren’t calling us,” Ms. Mendenhall explained.

Over the first year of participation in the OCM program, the oncology practice saw a 16% statistically significant reduction in hospital admissions (P = .005). The number of inpatient admissions per 100 patients dropped from 26.8 at baseline to 22.6 at the most recent follow-up in a report published simultaneously in the Journal of Oncology Practice.

Reduced admissions translated into a drop of $798,000 in inpatient costs per quarter over 1,600 patients, or $3.129 million in savings for the Centers for Medicare & Medicaid Services over the first year of participation in OCM, according to the researchers.

Patient satisfaction scores trended positively over the course of that year based on a review of blinded surveys that asked patients to rate clinical care, communication, access, information exchange, and other aspects of their experience.

Scores on those surveys were 8.03 on a scale of 0-10 (low to high) during the baseline period of January to September 2016, the researchers said. Scores were 8.29 and 8.26 for two follow-up surveys.

Ms. Mendenhall had no disclosures to report. Coauthors on the study provided disclosures related to Janssen Oncology, Pfizer, Amgen, Abbvie, Merck, Pharmacyclics, Bristol-Myers Squibb, Celgene, Genentech/Roche, AZTherapies, and Lilly. Two coauthors reported leadership, stock, or other ownership interests in Oncology Hematology Care/US Oncology.

SOURCE: Mendenhall M et al. Quality Care Symposium, Abstract 30.

PHOENIX – An initiative designed to reduce avoidable emergency room visits and hospitalizations cut admissions by 16%, according to a report from a large, independent, community-based oncology practice.

The program saved nearly $3.2 million in Medicare costs over the course of the year, said Molly Mendenhall, RN, of Oncology Hematology Care in Cincinnati.

“By keeping those patients out of the hospital, we were able to improve patient quality of life, and increase patient satisfaction by treating them in their home clinic instead of the hospital,” Ms. Mendenhall said at a symposium on quality care sponsored by the American Society of Clinical Oncology.

The campaign was developed in anticipation of participating in the Oncology Care Model (OCM), a program focused on providing coordinated and high-quality care for Medicare oncology patients at the same or lower cost.

Prior to participating in OCM, Ms. Mendenhall and her colleagues set up an after-hours phone triage system, proactive chemotherapy follow-up calls, and a Saturday-Sunday urgent care clinic designed to help avoid any unnecessary hospitalizations over the weekend.

They also set up a 2-hour structured OCM treatment planning visit to prioritize shared decision making between the patient and the clinical team regarding diagnosis, symptom management, financial assistance, and other aspects of care.

The most influential part of the initiative, according to Ms. Mendenhall, was a patient-directed “Call Us Early – Call Us First” campaign that included symptom management teaching sheets, a 34-page teaching book, and branded buttons, pens, and magnets all designed to emphasize the patient responsibility to use the phone.

“All of those previous steps really wouldn’t make a difference if the patients still weren’t calling us,” Ms. Mendenhall explained.

Over the first year of participation in the OCM program, the oncology practice saw a 16% statistically significant reduction in hospital admissions (P = .005). The number of inpatient admissions per 100 patients dropped from 26.8 at baseline to 22.6 at the most recent follow-up in a report published simultaneously in the Journal of Oncology Practice.

Reduced admissions translated into a drop of $798,000 in inpatient costs per quarter over 1,600 patients, or $3.129 million in savings for the Centers for Medicare & Medicaid Services over the first year of participation in OCM, according to the researchers.

Patient satisfaction scores trended positively over the course of that year based on a review of blinded surveys that asked patients to rate clinical care, communication, access, information exchange, and other aspects of their experience.

Scores on those surveys were 8.03 on a scale of 0-10 (low to high) during the baseline period of January to September 2016, the researchers said. Scores were 8.29 and 8.26 for two follow-up surveys.

Ms. Mendenhall had no disclosures to report. Coauthors on the study provided disclosures related to Janssen Oncology, Pfizer, Amgen, Abbvie, Merck, Pharmacyclics, Bristol-Myers Squibb, Celgene, Genentech/Roche, AZTherapies, and Lilly. Two coauthors reported leadership, stock, or other ownership interests in Oncology Hematology Care/US Oncology.

SOURCE: Mendenhall M et al. Quality Care Symposium, Abstract 30.

San Diego – State-of-the-art guidelines for treating sickle cell disease are actively being developed and could be released as early as the spring of 2019, according to Robert Liem, MD, chair of the American Society of Hematology coordination panel for the initiative.

The new clinical practice recommendations will expand on 2014 guidelines published by the National Heart, Lung, and Blood Institute in a way that will help both hematologists and nonhematologists who take care of patients with sickle cell disease, Dr. Liem said in a video interview at the annual meeting of the American Society of Hematology.

Five different guidelines are under development to cover different aspects of acute and chronic complications of sickle cell disease, including pain, cardiopulmonary and kidney disease, cerebrovascular disease, transfusion support, and stem cell transplantation.

Watch the video to learn more about the guideline effort from the perspective of Dr. Liem, who is also the director of the Comprehensive Sickle Cell Program at the Ann & Robert H. Lurie Children’s Hospital of Chicago.

San Diego – State-of-the-art guidelines for treating sickle cell disease are actively being developed and could be released as early as the spring of 2019, according to Robert Liem, MD, chair of the American Society of Hematology coordination panel for the initiative.

The new clinical practice recommendations will expand on 2014 guidelines published by the National Heart, Lung, and Blood Institute in a way that will help both hematologists and nonhematologists who take care of patients with sickle cell disease, Dr. Liem said in a video interview at the annual meeting of the American Society of Hematology.

Five different guidelines are under development to cover different aspects of acute and chronic complications of sickle cell disease, including pain, cardiopulmonary and kidney disease, cerebrovascular disease, transfusion support, and stem cell transplantation.

Watch the video to learn more about the guideline effort from the perspective of Dr. Liem, who is also the director of the Comprehensive Sickle Cell Program at the Ann & Robert H. Lurie Children’s Hospital of Chicago.

San Diego – State-of-the-art guidelines for treating sickle cell disease are actively being developed and could be released as early as the spring of 2019, according to Robert Liem, MD, chair of the American Society of Hematology coordination panel for the initiative.

The new clinical practice recommendations will expand on 2014 guidelines published by the National Heart, Lung, and Blood Institute in a way that will help both hematologists and nonhematologists who take care of patients with sickle cell disease, Dr. Liem said in a video interview at the annual meeting of the American Society of Hematology.

Five different guidelines are under development to cover different aspects of acute and chronic complications of sickle cell disease, including pain, cardiopulmonary and kidney disease, cerebrovascular disease, transfusion support, and stem cell transplantation.

Watch the video to learn more about the guideline effort from the perspective of Dr. Liem, who is also the director of the Comprehensive Sickle Cell Program at the Ann & Robert H. Lurie Children’s Hospital of Chicago.

SAN DIEGO – Emapalumab, an interferon gamma-blocking antibody, controls disease activity and has a favorable safety profile in patients with primary hemophagocytic lymphohistiocytosis (HLH), according to Franco Locatelli, MD, of the department of pediatric hematology and oncology at Ospedale Pediatrico Bambino Gesù, Rome.

Andrew D. Bowser/MDedge News

The recently approved agent should be considered a new therapeutic option for this rare and life-threatening syndrome because of its targeted mode of action, Dr. Locatelli and his coinvestigators reported at the annual meeting of the American Society of Hematology.

Multiple lines of evidence have pointed to interferon gamma as a “rational target” in this disease, and elevated levels of interferon gamma are consistently observed in patients with HLH, Dr. Locatelli said in a press conference at the meeting.

Emapalumab binds to its target with high affinity, recognizing both free and receptor-bound interferon gamma, he added.

Primary HLH is a rare, life-threatening syndrome of hyperinflammation, characterized by prolonged fever, cytopenias, and splenomegaly and hepatomegaly, among other clinical manifestations, Dr. Locatelli said.

In the open-label, single-arm, pivotal study, 34 children with primary HLH were treated: 7 who were treatment naive and 27 who had failed conventional HLH therapy.

The patients received emapalumab intravenously with concomitant dexamethasone for up to 8 weeks, or extended to the point of allogeneic hematopoietic stem cell transplantation (HSCT), if needed.

The study met its primary endpoint of overall response rate higher than 40%, Dr. Locatelli reported. The overall response rate was 64.7% for all 34 treated patients (95% confidence interval, 46% to 80%; P = .0031), and 63% for the 27 patients who had failed prior therapy (95% CI, 42% to 81%; P = .0134), reported data show.

Response was rapid, occurring at a median of 8 days after starting emapalumab, and patients were in response for a median of 75% of days during treatment, Dr. Locatelli said.

Common adverse events in the study included infections, infusion-related reactions, pyrexia, and hypertension, while one patient had disseminated histoplasmosis that resolved with appropriate treatment, according to investigators.

In light of these results, the Food and Drug Administration approved emapalumab on Nov. 20, 2018, for the treatment of pediatric and adult patients with primary HLH with refractory, recurrent or progressive disease, or intolerance to conventional HLH treatments.

There is “certainly room for enlarging the indication” to first-line treatment of HLH once a sufficient number of previously untreated patients have been treated with the monoclonal antibody, Dr. Locatelli said.

However, a randomized trial would not be feasible, he said. “It’s a very rare disease, and it would be almost impossible to run a prospective, randomized trial in a reasonable period of time.”

The study described by Dr. Locatelli was sponsored by Novimmune. Study authors provided disclosures related to Sobi, Novimmune, Rocket Pharmaceuticals, Inc., AB2Bio, Novartis, Eli Lilly, Sanofi, UCB, Pfizer, and Abbvie. Two authors reported employment with Novimmune.

SOURCE: Locatelli F et al. ASH 2018; Abstract LBA-6.

SAN DIEGO – Emapalumab, an interferon gamma-blocking antibody, controls disease activity and has a favorable safety profile in patients with primary hemophagocytic lymphohistiocytosis (HLH), according to Franco Locatelli, MD, of the department of pediatric hematology and oncology at Ospedale Pediatrico Bambino Gesù, Rome.

Andrew D. Bowser/MDedge News

The recently approved agent should be considered a new therapeutic option for this rare and life-threatening syndrome because of its targeted mode of action, Dr. Locatelli and his coinvestigators reported at the annual meeting of the American Society of Hematology.

Multiple lines of evidence have pointed to interferon gamma as a “rational target” in this disease, and elevated levels of interferon gamma are consistently observed in patients with HLH, Dr. Locatelli said in a press conference at the meeting.

Emapalumab binds to its target with high affinity, recognizing both free and receptor-bound interferon gamma, he added.

Primary HLH is a rare, life-threatening syndrome of hyperinflammation, characterized by prolonged fever, cytopenias, and splenomegaly and hepatomegaly, among other clinical manifestations, Dr. Locatelli said.

In the open-label, single-arm, pivotal study, 34 children with primary HLH were treated: 7 who were treatment naive and 27 who had failed conventional HLH therapy.

The patients received emapalumab intravenously with concomitant dexamethasone for up to 8 weeks, or extended to the point of allogeneic hematopoietic stem cell transplantation (HSCT), if needed.

The study met its primary endpoint of overall response rate higher than 40%, Dr. Locatelli reported. The overall response rate was 64.7% for all 34 treated patients (95% confidence interval, 46% to 80%; P = .0031), and 63% for the 27 patients who had failed prior therapy (95% CI, 42% to 81%; P = .0134), reported data show.

Response was rapid, occurring at a median of 8 days after starting emapalumab, and patients were in response for a median of 75% of days during treatment, Dr. Locatelli said.

Common adverse events in the study included infections, infusion-related reactions, pyrexia, and hypertension, while one patient had disseminated histoplasmosis that resolved with appropriate treatment, according to investigators.

In light of these results, the Food and Drug Administration approved emapalumab on Nov. 20, 2018, for the treatment of pediatric and adult patients with primary HLH with refractory, recurrent or progressive disease, or intolerance to conventional HLH treatments.

There is “certainly room for enlarging the indication” to first-line treatment of HLH once a sufficient number of previously untreated patients have been treated with the monoclonal antibody, Dr. Locatelli said.

However, a randomized trial would not be feasible, he said. “It’s a very rare disease, and it would be almost impossible to run a prospective, randomized trial in a reasonable period of time.”

The study described by Dr. Locatelli was sponsored by Novimmune. Study authors provided disclosures related to Sobi, Novimmune, Rocket Pharmaceuticals, Inc., AB2Bio, Novartis, Eli Lilly, Sanofi, UCB, Pfizer, and Abbvie. Two authors reported employment with Novimmune.

SOURCE: Locatelli F et al. ASH 2018; Abstract LBA-6.

SAN DIEGO – Emapalumab, an interferon gamma-blocking antibody, controls disease activity and has a favorable safety profile in patients with primary hemophagocytic lymphohistiocytosis (HLH), according to Franco Locatelli, MD, of the department of pediatric hematology and oncology at Ospedale Pediatrico Bambino Gesù, Rome.

Andrew D. Bowser/MDedge News

The recently approved agent should be considered a new therapeutic option for this rare and life-threatening syndrome because of its targeted mode of action, Dr. Locatelli and his coinvestigators reported at the annual meeting of the American Society of Hematology.

Multiple lines of evidence have pointed to interferon gamma as a “rational target” in this disease, and elevated levels of interferon gamma are consistently observed in patients with HLH, Dr. Locatelli said in a press conference at the meeting.

Emapalumab binds to its target with high affinity, recognizing both free and receptor-bound interferon gamma, he added.

Primary HLH is a rare, life-threatening syndrome of hyperinflammation, characterized by prolonged fever, cytopenias, and splenomegaly and hepatomegaly, among other clinical manifestations, Dr. Locatelli said.

In the open-label, single-arm, pivotal study, 34 children with primary HLH were treated: 7 who were treatment naive and 27 who had failed conventional HLH therapy.

The patients received emapalumab intravenously with concomitant dexamethasone for up to 8 weeks, or extended to the point of allogeneic hematopoietic stem cell transplantation (HSCT), if needed.

The study met its primary endpoint of overall response rate higher than 40%, Dr. Locatelli reported. The overall response rate was 64.7% for all 34 treated patients (95% confidence interval, 46% to 80%; P = .0031), and 63% for the 27 patients who had failed prior therapy (95% CI, 42% to 81%; P = .0134), reported data show.

Response was rapid, occurring at a median of 8 days after starting emapalumab, and patients were in response for a median of 75% of days during treatment, Dr. Locatelli said.

Common adverse events in the study included infections, infusion-related reactions, pyrexia, and hypertension, while one patient had disseminated histoplasmosis that resolved with appropriate treatment, according to investigators.

In light of these results, the Food and Drug Administration approved emapalumab on Nov. 20, 2018, for the treatment of pediatric and adult patients with primary HLH with refractory, recurrent or progressive disease, or intolerance to conventional HLH treatments.

There is “certainly room for enlarging the indication” to first-line treatment of HLH once a sufficient number of previously untreated patients have been treated with the monoclonal antibody, Dr. Locatelli said.

However, a randomized trial would not be feasible, he said. “It’s a very rare disease, and it would be almost impossible to run a prospective, randomized trial in a reasonable period of time.”

The study described by Dr. Locatelli was sponsored by Novimmune. Study authors provided disclosures related to Sobi, Novimmune, Rocket Pharmaceuticals, Inc., AB2Bio, Novartis, Eli Lilly, Sanofi, UCB, Pfizer, and Abbvie. Two authors reported employment with Novimmune.

SOURCE: Locatelli F et al. ASH 2018; Abstract LBA-6.

©ASH/Rodney White 2018

SAN DIEGO—Ixazomib improved progression-free survival (PFS) following autologous stem cell transplant (ASCT) in patients with newly diagnosed multiple myeloma (MM) in the TOURMALINE-MM3 trial.

The oral proteasome inhibitor improved PFS by 39% compared to placebo.

In addition, treatment with ixazomib was well tolerated, and there was a low discontinuation rate.

TOURMALINE-MM3 is the first-ever randomized, double-blind, placebo-controlled study of a proteasome inhibitor used as maintenance after ASCT, according to Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens in Greece.

Dr. Dimopoulos presented results from the trial at the 2018 ASH Annual Meeting (abstract 301).

He said the results suggest ixazomib represents a new treatment option for maintenance after ASCT in MM.

“Proteasome inhibitors have a different mechanism of action and may provide an alternative to lenalidomide,” Dr. Dimopoulos said.

He noted that ixazomib has a manageable toxicity profile and “convenient” weekly oral dosing, making it “well suited” for maintenance.

The TOURMALINE-MM3 study (NCT02181413) included 656 MM patients randomized post-ASCT to receive weekly ixazomib or placebo for up to 2 years.

The median PFS was 26.5 months for ixazomib and 21.3 months for placebo (hazard ratio=0.720; 95% confidence interval, 0.582-0.890; P=0.002).

At a median follow-up of 31 months, the median overall survival has not been reached in either treatment arm.

The discontinuation rate due to adverse events was 7% for ixazomib and 5% for placebo.

Ixazomib was associated with “low toxicity,” Dr Dimopoulos said, and there was no difference in the rates of new primary malignancies, at 3% in both arms.

When asked by an attendee whether ixazomib would become the standard of care for younger MM patients in this setting, Dr. Dimopoulos said the results show that ixazomib “is an option for patients, especially for those where a physician may believe that a proteasome inhibitor may be indicated.”

However, when pressed to comment on how ixazomib compares with lenalidomide for maintenance, Dr. Dimopoulos remarked that current maintenance studies are moving in the direction of combining therapies.

“I think that instead of saying, ‘Is ixazomib better than lenalidomide or vice-versa,’ it is better to see how one may combine those drugs in subsets of patients or even combine these drugs with other agents,” he said.

A manuscript describing results of the TOURMALINE-MM3 study is in press at The Lancet, with an expected online publication date of December 10, Dr. Dimopoulos said.

TOURMALINE-MM3 is sponsored by Takeda (Millennium), the maker of ixazomib.

Dr. Dimopoulos reported honoraria and consultancy with Janssen, Takeda Pharmaceuticals, Amgen, Bristol-Myers Squibb, and Celgene. 

©ASH/Rodney White 2018

SAN DIEGO—Ixazomib improved progression-free survival (PFS) following autologous stem cell transplant (ASCT) in patients with newly diagnosed multiple myeloma (MM) in the TOURMALINE-MM3 trial.

The oral proteasome inhibitor improved PFS by 39% compared to placebo.

In addition, treatment with ixazomib was well tolerated, and there was a low discontinuation rate.

TOURMALINE-MM3 is the first-ever randomized, double-blind, placebo-controlled study of a proteasome inhibitor used as maintenance after ASCT, according to Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens in Greece.

Dr. Dimopoulos presented results from the trial at the 2018 ASH Annual Meeting (abstract 301).

He said the results suggest ixazomib represents a new treatment option for maintenance after ASCT in MM.

“Proteasome inhibitors have a different mechanism of action and may provide an alternative to lenalidomide,” Dr. Dimopoulos said.

He noted that ixazomib has a manageable toxicity profile and “convenient” weekly oral dosing, making it “well suited” for maintenance.

The TOURMALINE-MM3 study (NCT02181413) included 656 MM patients randomized post-ASCT to receive weekly ixazomib or placebo for up to 2 years.

The median PFS was 26.5 months for ixazomib and 21.3 months for placebo (hazard ratio=0.720; 95% confidence interval, 0.582-0.890; P=0.002).

At a median follow-up of 31 months, the median overall survival has not been reached in either treatment arm.

The discontinuation rate due to adverse events was 7% for ixazomib and 5% for placebo.

Ixazomib was associated with “low toxicity,” Dr Dimopoulos said, and there was no difference in the rates of new primary malignancies, at 3% in both arms.

When asked by an attendee whether ixazomib would become the standard of care for younger MM patients in this setting, Dr. Dimopoulos said the results show that ixazomib “is an option for patients, especially for those where a physician may believe that a proteasome inhibitor may be indicated.”

However, when pressed to comment on how ixazomib compares with lenalidomide for maintenance, Dr. Dimopoulos remarked that current maintenance studies are moving in the direction of combining therapies.

“I think that instead of saying, ‘Is ixazomib better than lenalidomide or vice-versa,’ it is better to see how one may combine those drugs in subsets of patients or even combine these drugs with other agents,” he said.

A manuscript describing results of the TOURMALINE-MM3 study is in press at The Lancet, with an expected online publication date of December 10, Dr. Dimopoulos said.

TOURMALINE-MM3 is sponsored by Takeda (Millennium), the maker of ixazomib.

Dr. Dimopoulos reported honoraria and consultancy with Janssen, Takeda Pharmaceuticals, Amgen, Bristol-Myers Squibb, and Celgene. 

©ASH/Rodney White 2018

SAN DIEGO—Ixazomib improved progression-free survival (PFS) following autologous stem cell transplant (ASCT) in patients with newly diagnosed multiple myeloma (MM) in the TOURMALINE-MM3 trial.

The oral proteasome inhibitor improved PFS by 39% compared to placebo.

In addition, treatment with ixazomib was well tolerated, and there was a low discontinuation rate.

TOURMALINE-MM3 is the first-ever randomized, double-blind, placebo-controlled study of a proteasome inhibitor used as maintenance after ASCT, according to Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens in Greece.

Dr. Dimopoulos presented results from the trial at the 2018 ASH Annual Meeting (abstract 301).

He said the results suggest ixazomib represents a new treatment option for maintenance after ASCT in MM.

“Proteasome inhibitors have a different mechanism of action and may provide an alternative to lenalidomide,” Dr. Dimopoulos said.

He noted that ixazomib has a manageable toxicity profile and “convenient” weekly oral dosing, making it “well suited” for maintenance.

The TOURMALINE-MM3 study (NCT02181413) included 656 MM patients randomized post-ASCT to receive weekly ixazomib or placebo for up to 2 years.

The median PFS was 26.5 months for ixazomib and 21.3 months for placebo (hazard ratio=0.720; 95% confidence interval, 0.582-0.890; P=0.002).

At a median follow-up of 31 months, the median overall survival has not been reached in either treatment arm.

The discontinuation rate due to adverse events was 7% for ixazomib and 5% for placebo.

Ixazomib was associated with “low toxicity,” Dr Dimopoulos said, and there was no difference in the rates of new primary malignancies, at 3% in both arms.

When asked by an attendee whether ixazomib would become the standard of care for younger MM patients in this setting, Dr. Dimopoulos said the results show that ixazomib “is an option for patients, especially for those where a physician may believe that a proteasome inhibitor may be indicated.”

However, when pressed to comment on how ixazomib compares with lenalidomide for maintenance, Dr. Dimopoulos remarked that current maintenance studies are moving in the direction of combining therapies.

“I think that instead of saying, ‘Is ixazomib better than lenalidomide or vice-versa,’ it is better to see how one may combine those drugs in subsets of patients or even combine these drugs with other agents,” he said.

A manuscript describing results of the TOURMALINE-MM3 study is in press at The Lancet, with an expected online publication date of December 10, Dr. Dimopoulos said.

TOURMALINE-MM3 is sponsored by Takeda (Millennium), the maker of ixazomib.

Dr. Dimopoulos reported honoraria and consultancy with Janssen, Takeda Pharmaceuticals, Amgen, Bristol-Myers Squibb, and Celgene. 

SAN DIEGO – Lower-than-usual doses of rituximab may be sufficient in patients with acquired thrombotic thrombocytopenic purpura (TTP), results of a recent pilot safety and efficacy study suggest.

Patients receiving just 100 mg/week for 4 weeks had rates of relapse and exacerbation that were favorable, compared with historical controls, according to investigator Jeffrey I. Zwicker, MD, of Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston. He presented the findings at the annual meeting of the American Society of Hematology.

However, the low-dose treatment was not without side effects, according to Dr. Zwicker, who described one case of acute respiratory failure out of the 19 patients enrolled in the ART (Adjuvant Rituximab in TTP) study.

“The likely benefit is cost savings, rather than less toxicity,” Dr. Zwicker said of the low-dose rituximab regimen.

Out of 19 patients enrolled in ART, 18 were eligible to receive the study treatment, which included low-dose rituximab plus standard plasma exchange and corticosteroids.

Following this initial therapy, all patients had a response, defined as a platelet count 150,000/mcL or greater for 2 consecutive days, with a median time to response of 5 days.

There were two exacerbations (12%) at 30 days after stopping plasma exchange and no cases of refractory TTP, which compared favorably to historical controls, Dr. Zwicker said.

The rate of relapse at 2 years was 28%, which again compared favorably with a historical control data repository in which the rate of relapse at 2 years was 51%.

One patient in the study suffered a case of acute respiratory failure requiring intubation during the third rituximab infusion and was ultimately placed on extracorporeal membrane oxygenation.

“The patient did survive, but this is just a reminder that there are potential side effects, even with lower doses of rituximab,” Dr. Zwicker said.

A few other serious adverse events – including central line infection and bacteremia in one patient – were more likely related to the plasma exchange, he added.

These results with low-dose rituximab are consistent with findings that rituximab 375 mg/m² for four doses reduces the incidence of exacerbation and refractory disease and prevents or delays relapses, according to Dr. Zwicker and his coinvestigators, including J. Evan Sadler, MD, PhD, of Washington University, St. Louis, who initiated the study.

The typical TTP regimen of rituximab 375 mg/m² for four weekly doses is borrowed from protocols for B-cell lymphomas; however, the B-cell mass in nonmalignant disease is likely to be much less than in lymphoproliferative disorders, Dr. Zwicker told attendees.

“The benefit, principally, of lower-dose rituximab is saving of thousands upon thousands of dollars,” Dr. Zwicker said.

This is not the only data set to suggest a potential role for lower-dose rituximab, he added, noting that a recently published retrospective analysis showed “fairly similar” treatment-free survival rates for standard rituximab and a reduced-dose regimen. There also are case series in other autoimmune cytopenias, namely idiopathic thrombocytopenic purpura and pure red cell aplasia, that provide evidence in support of low-dose rituximab, he added.

Dr. Zwicker reported research funding with Incyte and Quercegen, and consultancy with Parexel. Dr. Sadler reported consultancy with Ablynx.

SOURCE: Zwicker JI et al. ASH 2018, Abstract 374.

SAN DIEGO – Lower-than-usual doses of rituximab may be sufficient in patients with acquired thrombotic thrombocytopenic purpura (TTP), results of a recent pilot safety and efficacy study suggest.

Patients receiving just 100 mg/week for 4 weeks had rates of relapse and exacerbation that were favorable, compared with historical controls, according to investigator Jeffrey I. Zwicker, MD, of Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston. He presented the findings at the annual meeting of the American Society of Hematology.

However, the low-dose treatment was not without side effects, according to Dr. Zwicker, who described one case of acute respiratory failure out of the 19 patients enrolled in the ART (Adjuvant Rituximab in TTP) study.

“The likely benefit is cost savings, rather than less toxicity,” Dr. Zwicker said of the low-dose rituximab regimen.

Out of 19 patients enrolled in ART, 18 were eligible to receive the study treatment, which included low-dose rituximab plus standard plasma exchange and corticosteroids.

Following this initial therapy, all patients had a response, defined as a platelet count 150,000/mcL or greater for 2 consecutive days, with a median time to response of 5 days.

There were two exacerbations (12%) at 30 days after stopping plasma exchange and no cases of refractory TTP, which compared favorably to historical controls, Dr. Zwicker said.

The rate of relapse at 2 years was 28%, which again compared favorably with a historical control data repository in which the rate of relapse at 2 years was 51%.

One patient in the study suffered a case of acute respiratory failure requiring intubation during the third rituximab infusion and was ultimately placed on extracorporeal membrane oxygenation.

“The patient did survive, but this is just a reminder that there are potential side effects, even with lower doses of rituximab,” Dr. Zwicker said.

A few other serious adverse events – including central line infection and bacteremia in one patient – were more likely related to the plasma exchange, he added.

These results with low-dose rituximab are consistent with findings that rituximab 375 mg/m² for four doses reduces the incidence of exacerbation and refractory disease and prevents or delays relapses, according to Dr. Zwicker and his coinvestigators, including J. Evan Sadler, MD, PhD, of Washington University, St. Louis, who initiated the study.

The typical TTP regimen of rituximab 375 mg/m² for four weekly doses is borrowed from protocols for B-cell lymphomas; however, the B-cell mass in nonmalignant disease is likely to be much less than in lymphoproliferative disorders, Dr. Zwicker told attendees.

“The benefit, principally, of lower-dose rituximab is saving of thousands upon thousands of dollars,” Dr. Zwicker said.

This is not the only data set to suggest a potential role for lower-dose rituximab, he added, noting that a recently published retrospective analysis showed “fairly similar” treatment-free survival rates for standard rituximab and a reduced-dose regimen. There also are case series in other autoimmune cytopenias, namely idiopathic thrombocytopenic purpura and pure red cell aplasia, that provide evidence in support of low-dose rituximab, he added.

Dr. Zwicker reported research funding with Incyte and Quercegen, and consultancy with Parexel. Dr. Sadler reported consultancy with Ablynx.

SOURCE: Zwicker JI et al. ASH 2018, Abstract 374.

SAN DIEGO – Lower-than-usual doses of rituximab may be sufficient in patients with acquired thrombotic thrombocytopenic purpura (TTP), results of a recent pilot safety and efficacy study suggest.

Patients receiving just 100 mg/week for 4 weeks had rates of relapse and exacerbation that were favorable, compared with historical controls, according to investigator Jeffrey I. Zwicker, MD, of Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston. He presented the findings at the annual meeting of the American Society of Hematology.

However, the low-dose treatment was not without side effects, according to Dr. Zwicker, who described one case of acute respiratory failure out of the 19 patients enrolled in the ART (Adjuvant Rituximab in TTP) study.

“The likely benefit is cost savings, rather than less toxicity,” Dr. Zwicker said of the low-dose rituximab regimen.

Out of 19 patients enrolled in ART, 18 were eligible to receive the study treatment, which included low-dose rituximab plus standard plasma exchange and corticosteroids.

Following this initial therapy, all patients had a response, defined as a platelet count 150,000/mcL or greater for 2 consecutive days, with a median time to response of 5 days.

There were two exacerbations (12%) at 30 days after stopping plasma exchange and no cases of refractory TTP, which compared favorably to historical controls, Dr. Zwicker said.

The rate of relapse at 2 years was 28%, which again compared favorably with a historical control data repository in which the rate of relapse at 2 years was 51%.

One patient in the study suffered a case of acute respiratory failure requiring intubation during the third rituximab infusion and was ultimately placed on extracorporeal membrane oxygenation.

“The patient did survive, but this is just a reminder that there are potential side effects, even with lower doses of rituximab,” Dr. Zwicker said.

A few other serious adverse events – including central line infection and bacteremia in one patient – were more likely related to the plasma exchange, he added.

These results with low-dose rituximab are consistent with findings that rituximab 375 mg/m² for four doses reduces the incidence of exacerbation and refractory disease and prevents or delays relapses, according to Dr. Zwicker and his coinvestigators, including J. Evan Sadler, MD, PhD, of Washington University, St. Louis, who initiated the study.

The typical TTP regimen of rituximab 375 mg/m² for four weekly doses is borrowed from protocols for B-cell lymphomas; however, the B-cell mass in nonmalignant disease is likely to be much less than in lymphoproliferative disorders, Dr. Zwicker told attendees.

“The benefit, principally, of lower-dose rituximab is saving of thousands upon thousands of dollars,” Dr. Zwicker said.

This is not the only data set to suggest a potential role for lower-dose rituximab, he added, noting that a recently published retrospective analysis showed “fairly similar” treatment-free survival rates for standard rituximab and a reduced-dose regimen. There also are case series in other autoimmune cytopenias, namely idiopathic thrombocytopenic purpura and pure red cell aplasia, that provide evidence in support of low-dose rituximab, he added.

Dr. Zwicker reported research funding with Incyte and Quercegen, and consultancy with Parexel. Dr. Sadler reported consultancy with Ablynx.

SOURCE: Zwicker JI et al. ASH 2018, Abstract 374.

© ASH/Scott Morgan 2018

SAN DIEGO—Results of the randomized, phase 3 Medalist trial show that the erythroid maturation agent luspatercept can reduce transfusion burden in patients with anemia due to myelodysplastic syndromes (MDS) and ring sideroblasts.

Almost 38% of luspatercept-treated patients achieved red blood cell (RBC) transfusion independence for 8 weeks or more, compared with 13% of patients receiving placebo.

And 28% of luspatercept-treated patients achieved transfusion independence for 12 weeks or more, compared to 8% in the placebo group.

Investigators reported these results as abstract 1 at the 2018 ASH Annual Meeting.

Treatment with luspatercept was “very well tolerated,” and responses were durable, with approximately 40% of patients remaining transfusion-free after 1 year of therapy, said senior investigator Alan F. List, MD, of Moffitt Cancer Center in Tampa, Florida, during a press conference at the meeting.

The first-in-class erythroid maturation agent is being developed as a treatment for anemia related to MDS and beta-thalassemia, Dr. List said.

“Luspatercept is a potential new therapy that we think could be very effective in patients with lower-risk MDS with ring sideroblasts who are red blood cell transfusion-dependent,” Dr. List affirmed.

Luspatercept is a soluble receptor chimera that binds to an array of ligands in the TGF-β superfamily, which is known to be very important in suppressing erythropoiesis in patients with MDS, Dr. List noted.

The Medalist study (NCT02631070) included patients with very low-, low-, or intermediate-risk disease and ring sideroblasts who were RBC transfusion-dependent and were refractory to, unresponsive to, or ineligible for first-line treatment with an erythropoiesis-stimulating agent (ESA).

A total of 153 patients were randomized to receive luspatercept at 1.0 mg/kg, administered subcutaneously every 21 days for at least 24 weeks, while 76 were randomized to placebo every 21 days.

The primary endpoint was the proportion of patients achieving RBC transfusion independence for at least 8 weeks during the first 24 weeks of treatment.

The primary endpoint was achieved by 37.9% of luspatercept-treated patients and 13.2% of placebo-treated patients (P<0.0001).

The luspatercept-treated patients also had a higher rate of erythroid response compared with the placebo group, at 52.9% and 11.8%, respectively (P<0.0001).

The investigators reported no differences in treatment-emergent adverse events, severe adverse events, or frequency of progression of acute myeloid leukemia (AML).

The safety profile was consistent with that of the phase 2 PACE-MDS study, which included treatment-related grade 3 myalgia (2%), increased blast cell count (2%), and general physical health deterioration (2%).

“This was a very clean drug and a very safe drug,” Dr. List said.

The decision to study luspatercept in patients with ring sideroblasts was based on results of the phase 2 PACE study showing a higher response rate in that subset of MDS patients, according to Dr. List.

The PACE study also included a small number of patients who had not previously received an ESA.

Currently underway is a phase 3 trial (NCT03682536) investigating luspatercept in ESA-naïve lower-risk MDS patients with anemia who require RBC transfusions.

Luspatercept would be a useful therapy to have in clinic for patients with ring sideroblasts, which represent about 25% of patients overall, according to MDS expert David Steensma, MD, of Dana-Farber Cancer Institute and Harvard Medical School in Boston, Massachusetts.

“It’s been 12 years since we had an FDA-approved drug in MDS, and there have been 7 in acute myeloid leukemia in the last year and a half, so it’s our turn, I think,” said Dr. Steensma, who moderated the press conference.

The Medalist study was sponsored by Celgene in collaboration with Acceleron Pharma, Inc.

Dr. List reported research funding from Celgene. 

© ASH/Scott Morgan 2018

SAN DIEGO—Results of the randomized, phase 3 Medalist trial show that the erythroid maturation agent luspatercept can reduce transfusion burden in patients with anemia due to myelodysplastic syndromes (MDS) and ring sideroblasts.

Almost 38% of luspatercept-treated patients achieved red blood cell (RBC) transfusion independence for 8 weeks or more, compared with 13% of patients receiving placebo.

And 28% of luspatercept-treated patients achieved transfusion independence for 12 weeks or more, compared to 8% in the placebo group.

Investigators reported these results as abstract 1 at the 2018 ASH Annual Meeting.

Treatment with luspatercept was “very well tolerated,” and responses were durable, with approximately 40% of patients remaining transfusion-free after 1 year of therapy, said senior investigator Alan F. List, MD, of Moffitt Cancer Center in Tampa, Florida, during a press conference at the meeting.

The first-in-class erythroid maturation agent is being developed as a treatment for anemia related to MDS and beta-thalassemia, Dr. List said.

“Luspatercept is a potential new therapy that we think could be very effective in patients with lower-risk MDS with ring sideroblasts who are red blood cell transfusion-dependent,” Dr. List affirmed.

Luspatercept is a soluble receptor chimera that binds to an array of ligands in the TGF-β superfamily, which is known to be very important in suppressing erythropoiesis in patients with MDS, Dr. List noted.

The Medalist study (NCT02631070) included patients with very low-, low-, or intermediate-risk disease and ring sideroblasts who were RBC transfusion-dependent and were refractory to, unresponsive to, or ineligible for first-line treatment with an erythropoiesis-stimulating agent (ESA).

A total of 153 patients were randomized to receive luspatercept at 1.0 mg/kg, administered subcutaneously every 21 days for at least 24 weeks, while 76 were randomized to placebo every 21 days.

The primary endpoint was the proportion of patients achieving RBC transfusion independence for at least 8 weeks during the first 24 weeks of treatment.

The primary endpoint was achieved by 37.9% of luspatercept-treated patients and 13.2% of placebo-treated patients (P<0.0001).

The luspatercept-treated patients also had a higher rate of erythroid response compared with the placebo group, at 52.9% and 11.8%, respectively (P<0.0001).

The investigators reported no differences in treatment-emergent adverse events, severe adverse events, or frequency of progression of acute myeloid leukemia (AML).

The safety profile was consistent with that of the phase 2 PACE-MDS study, which included treatment-related grade 3 myalgia (2%), increased blast cell count (2%), and general physical health deterioration (2%).

“This was a very clean drug and a very safe drug,” Dr. List said.

The decision to study luspatercept in patients with ring sideroblasts was based on results of the phase 2 PACE study showing a higher response rate in that subset of MDS patients, according to Dr. List.

The PACE study also included a small number of patients who had not previously received an ESA.

Currently underway is a phase 3 trial (NCT03682536) investigating luspatercept in ESA-naïve lower-risk MDS patients with anemia who require RBC transfusions.

Luspatercept would be a useful therapy to have in clinic for patients with ring sideroblasts, which represent about 25% of patients overall, according to MDS expert David Steensma, MD, of Dana-Farber Cancer Institute and Harvard Medical School in Boston, Massachusetts.

“It’s been 12 years since we had an FDA-approved drug in MDS, and there have been 7 in acute myeloid leukemia in the last year and a half, so it’s our turn, I think,” said Dr. Steensma, who moderated the press conference.

The Medalist study was sponsored by Celgene in collaboration with Acceleron Pharma, Inc.

Dr. List reported research funding from Celgene. 

© ASH/Scott Morgan 2018

SAN DIEGO—Results of the randomized, phase 3 Medalist trial show that the erythroid maturation agent luspatercept can reduce transfusion burden in patients with anemia due to myelodysplastic syndromes (MDS) and ring sideroblasts.

Almost 38% of luspatercept-treated patients achieved red blood cell (RBC) transfusion independence for 8 weeks or more, compared with 13% of patients receiving placebo.

And 28% of luspatercept-treated patients achieved transfusion independence for 12 weeks or more, compared to 8% in the placebo group.

Investigators reported these results as abstract 1 at the 2018 ASH Annual Meeting.

Treatment with luspatercept was “very well tolerated,” and responses were durable, with approximately 40% of patients remaining transfusion-free after 1 year of therapy, said senior investigator Alan F. List, MD, of Moffitt Cancer Center in Tampa, Florida, during a press conference at the meeting.

The first-in-class erythroid maturation agent is being developed as a treatment for anemia related to MDS and beta-thalassemia, Dr. List said.

“Luspatercept is a potential new therapy that we think could be very effective in patients with lower-risk MDS with ring sideroblasts who are red blood cell transfusion-dependent,” Dr. List affirmed.

Luspatercept is a soluble receptor chimera that binds to an array of ligands in the TGF-β superfamily, which is known to be very important in suppressing erythropoiesis in patients with MDS, Dr. List noted.

The Medalist study (NCT02631070) included patients with very low-, low-, or intermediate-risk disease and ring sideroblasts who were RBC transfusion-dependent and were refractory to, unresponsive to, or ineligible for first-line treatment with an erythropoiesis-stimulating agent (ESA).

A total of 153 patients were randomized to receive luspatercept at 1.0 mg/kg, administered subcutaneously every 21 days for at least 24 weeks, while 76 were randomized to placebo every 21 days.

The primary endpoint was the proportion of patients achieving RBC transfusion independence for at least 8 weeks during the first 24 weeks of treatment.

The primary endpoint was achieved by 37.9% of luspatercept-treated patients and 13.2% of placebo-treated patients (P<0.0001).

The luspatercept-treated patients also had a higher rate of erythroid response compared with the placebo group, at 52.9% and 11.8%, respectively (P<0.0001).

The investigators reported no differences in treatment-emergent adverse events, severe adverse events, or frequency of progression of acute myeloid leukemia (AML).

The safety profile was consistent with that of the phase 2 PACE-MDS study, which included treatment-related grade 3 myalgia (2%), increased blast cell count (2%), and general physical health deterioration (2%).

“This was a very clean drug and a very safe drug,” Dr. List said.

The decision to study luspatercept in patients with ring sideroblasts was based on results of the phase 2 PACE study showing a higher response rate in that subset of MDS patients, according to Dr. List.

The PACE study also included a small number of patients who had not previously received an ESA.

Currently underway is a phase 3 trial (NCT03682536) investigating luspatercept in ESA-naïve lower-risk MDS patients with anemia who require RBC transfusions.

Luspatercept would be a useful therapy to have in clinic for patients with ring sideroblasts, which represent about 25% of patients overall, according to MDS expert David Steensma, MD, of Dana-Farber Cancer Institute and Harvard Medical School in Boston, Massachusetts.

“It’s been 12 years since we had an FDA-approved drug in MDS, and there have been 7 in acute myeloid leukemia in the last year and a half, so it’s our turn, I think,” said Dr. Steensma, who moderated the press conference.

The Medalist study was sponsored by Celgene in collaboration with Acceleron Pharma, Inc.

Dr. List reported research funding from Celgene. 

SAN DIEGO – Ixazomib improved progression-free survival following autologous stem cell transplantation (ASCT) in patients with newly diagnosed multiple myeloma, according to results of a double-blind, randomized, placebo-controlled, phase 3 trial.

Andrew Bowser/MDedge News

Treatment with the oral proteasome inhibitor for 24 months was well tolerated, had a low discontinuation rate, and improved progression-free survival by 39% versus placebo, according to Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens.

These findings suggest ixazomib (Ninlaro) represents a “new treatment option for maintenance after transplantation,” Dr. Dimopoulos said at the annual meeting of the American Society of Hematology.

The trial, known as TOURMALINE-MM3, is the first-ever randomized, double-blind, placebo-controlled study of a proteasome inhibitor used as maintenance after ASCT, according to Dr. Dimopoulos. Lenalidomide is approved in that setting, but 29% of patients who start the treatment discontinue because of treatment-related adverse events.

“Proteasome inhibitors have a different mechanism of action and may provide an alternative to lenalidomide,” Dr. Dimopoulos said at an oral abstract session. Ixazomib has a manageable toxicity profile and “convenient” weekly oral dosing, making it “well suited” for maintenance.

When asked by an attendee whether ixazomib would become “the standard of care” for younger patients with myeloma in this setting, Dr. Dimopoulos replied the results show that ixazomib “is an option for patients, especially for those where a physician may believe that a proteasome inhibitor may be indicated.”

However, when pressed by an attendee to comment on how ixazomib compares with lenalidomide for maintenance, Dr. Dimopoulos remarked that current maintenance studies are moving in the direction of combining therapies.

“I think that instead of saying, ‘is ixazomib better than lenalidomide?’ or vice versa, it is better to see how one may combine those drugs in subsets of patients, or even combine these drugs with other agents,” he said.

The TOURMALINE-MM3 study included 656 patients randomized posttransplantation to receive weekly ixazomib or placebo for up to 2 years.

The median progression-free survival was 26.5 months for ixazomib versus 21.3 months for placebo (P = .002; hazard ratio, 0.720; 95% confidence interval, 0.582-0.890). Median overall survival had not been reached in either ixazomib or placebo arms as of this report, with a median follow-up of 31 months.

The discontinuation rate was 7% for ixazomib versus 5% for placebo, according to the investigator. Moreover, ixazomib was associated with “low toxicity” and no difference in the rates of new primary malignancies, at 3% in both arms.

A manuscript describing results of the TOURMALINE-MM3 study is in press in the Lancet, with an expected online publication date of Dec. 10, Dr. Dimopoulos told attendees. Other studies are ongoing to evaluate ixazomib combinations and treatment to progression in this setting.

TOURMALINE-MM3 is sponsored by Takeda (Millennium), the maker of ixazomib. Dr. Dimopoulos reported honoraria and consultancy with Janssen, Takeda Pharmaceutical, Amgen, Bristol-Myers Squibb, and Celgene.

SOURCE: Dimopoulos MA et al. ASH 2018, Abstract 301.

SAN DIEGO – Ixazomib improved progression-free survival following autologous stem cell transplantation (ASCT) in patients with newly diagnosed multiple myeloma, according to results of a double-blind, randomized, placebo-controlled, phase 3 trial.

Andrew Bowser/MDedge News

Treatment with the oral proteasome inhibitor for 24 months was well tolerated, had a low discontinuation rate, and improved progression-free survival by 39% versus placebo, according to Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens.

These findings suggest ixazomib (Ninlaro) represents a “new treatment option for maintenance after transplantation,” Dr. Dimopoulos said at the annual meeting of the American Society of Hematology.

The trial, known as TOURMALINE-MM3, is the first-ever randomized, double-blind, placebo-controlled study of a proteasome inhibitor used as maintenance after ASCT, according to Dr. Dimopoulos. Lenalidomide is approved in that setting, but 29% of patients who start the treatment discontinue because of treatment-related adverse events.

“Proteasome inhibitors have a different mechanism of action and may provide an alternative to lenalidomide,” Dr. Dimopoulos said at an oral abstract session. Ixazomib has a manageable toxicity profile and “convenient” weekly oral dosing, making it “well suited” for maintenance.

When asked by an attendee whether ixazomib would become “the standard of care” for younger patients with myeloma in this setting, Dr. Dimopoulos replied the results show that ixazomib “is an option for patients, especially for those where a physician may believe that a proteasome inhibitor may be indicated.”

However, when pressed by an attendee to comment on how ixazomib compares with lenalidomide for maintenance, Dr. Dimopoulos remarked that current maintenance studies are moving in the direction of combining therapies.

“I think that instead of saying, ‘is ixazomib better than lenalidomide?’ or vice versa, it is better to see how one may combine those drugs in subsets of patients, or even combine these drugs with other agents,” he said.

The TOURMALINE-MM3 study included 656 patients randomized posttransplantation to receive weekly ixazomib or placebo for up to 2 years.

The median progression-free survival was 26.5 months for ixazomib versus 21.3 months for placebo (P = .002; hazard ratio, 0.720; 95% confidence interval, 0.582-0.890). Median overall survival had not been reached in either ixazomib or placebo arms as of this report, with a median follow-up of 31 months.

The discontinuation rate was 7% for ixazomib versus 5% for placebo, according to the investigator. Moreover, ixazomib was associated with “low toxicity” and no difference in the rates of new primary malignancies, at 3% in both arms.

A manuscript describing results of the TOURMALINE-MM3 study is in press in the Lancet, with an expected online publication date of Dec. 10, Dr. Dimopoulos told attendees. Other studies are ongoing to evaluate ixazomib combinations and treatment to progression in this setting.

TOURMALINE-MM3 is sponsored by Takeda (Millennium), the maker of ixazomib. Dr. Dimopoulos reported honoraria and consultancy with Janssen, Takeda Pharmaceutical, Amgen, Bristol-Myers Squibb, and Celgene.

SOURCE: Dimopoulos MA et al. ASH 2018, Abstract 301.

SAN DIEGO – Ixazomib improved progression-free survival following autologous stem cell transplantation (ASCT) in patients with newly diagnosed multiple myeloma, according to results of a double-blind, randomized, placebo-controlled, phase 3 trial.

Andrew Bowser/MDedge News

Treatment with the oral proteasome inhibitor for 24 months was well tolerated, had a low discontinuation rate, and improved progression-free survival by 39% versus placebo, according to Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens.

These findings suggest ixazomib (Ninlaro) represents a “new treatment option for maintenance after transplantation,” Dr. Dimopoulos said at the annual meeting of the American Society of Hematology.

The trial, known as TOURMALINE-MM3, is the first-ever randomized, double-blind, placebo-controlled study of a proteasome inhibitor used as maintenance after ASCT, according to Dr. Dimopoulos. Lenalidomide is approved in that setting, but 29% of patients who start the treatment discontinue because of treatment-related adverse events.

“Proteasome inhibitors have a different mechanism of action and may provide an alternative to lenalidomide,” Dr. Dimopoulos said at an oral abstract session. Ixazomib has a manageable toxicity profile and “convenient” weekly oral dosing, making it “well suited” for maintenance.

When asked by an attendee whether ixazomib would become “the standard of care” for younger patients with myeloma in this setting, Dr. Dimopoulos replied the results show that ixazomib “is an option for patients, especially for those where a physician may believe that a proteasome inhibitor may be indicated.”

However, when pressed by an attendee to comment on how ixazomib compares with lenalidomide for maintenance, Dr. Dimopoulos remarked that current maintenance studies are moving in the direction of combining therapies.

“I think that instead of saying, ‘is ixazomib better than lenalidomide?’ or vice versa, it is better to see how one may combine those drugs in subsets of patients, or even combine these drugs with other agents,” he said.

The TOURMALINE-MM3 study included 656 patients randomized posttransplantation to receive weekly ixazomib or placebo for up to 2 years.

The median progression-free survival was 26.5 months for ixazomib versus 21.3 months for placebo (P = .002; hazard ratio, 0.720; 95% confidence interval, 0.582-0.890). Median overall survival had not been reached in either ixazomib or placebo arms as of this report, with a median follow-up of 31 months.

The discontinuation rate was 7% for ixazomib versus 5% for placebo, according to the investigator. Moreover, ixazomib was associated with “low toxicity” and no difference in the rates of new primary malignancies, at 3% in both arms.

A manuscript describing results of the TOURMALINE-MM3 study is in press in the Lancet, with an expected online publication date of Dec. 10, Dr. Dimopoulos told attendees. Other studies are ongoing to evaluate ixazomib combinations and treatment to progression in this setting.

TOURMALINE-MM3 is sponsored by Takeda (Millennium), the maker of ixazomib. Dr. Dimopoulos reported honoraria and consultancy with Janssen, Takeda Pharmaceutical, Amgen, Bristol-Myers Squibb, and Celgene.

SOURCE: Dimopoulos MA et al. ASH 2018, Abstract 301.