ASH 2014

SAN FRANCISCO—The anti-CD19 antibody M0R208 has demonstrated encouraging single-agent activity in patients with relapsed or refractory non-Hodgkin lymphoma (NHL), according to a presenter at the 2014 ASH Annual Meeting.

“It is encouraging to see results in an NHL study that selects a different target than CD20,” said Kristie Blum, MD, of The Ohio State University in Columbus.

“In particular, it is good to see activity in elderly large-cell lymphoma patients.”

MOR208 is an Fc-engineered humanized monoclonal antibody that targets the CD19 antigen.

“It possesses significantly enhanced antibody-dependent cell-mediated cytotoxicity, a key mechanism for tumor cell killing,” Dr Blum explained. “We have seen previous responses in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL).”

In fact, MOR208 recently received fast-track designation from the US Food and Drug Administration to treat DLBCL.

At ASH, Dr Blum reported on a non-randomized, phase 2a study designed to assess the efficacy and safety of single-agent MOR208 in adults with relapsed or refractory NHL (abstract 3089). The trial was sponsored by MorphoSys AG, the company developing MOR208.

The study included 89 patients—35 with DLBCL, 31 with FL, 12 with mantle cell lymphoma (MCL), and 11 with other indolent NHLs (iNHLs). The patients had a median age of 67 years, were previously treated with rituximab, and were not candidates for high-dose therapy with stem cell support.

The patients were treated over 56 days. MOR208 was given intravenously at 12 mg/kg as 8 weekly doses on days 1, 8, 15, and 22 of each cycle. Patients with at least stable disease continued treatment for another cycle.

After completing 12 weekly doses of treatment, responding patients received maintenance MOR208 every 2 or 4 weeks, depending on the investigator’s decision, until progression.

The results showed overall response rates of 26% for DLBCL patients, 23% for FL patients, and 36% in iNHL patients. No MCL patients responded.

There were 2 complete responses in the DLBCL cohort and 1 complete response each in the FL and iNHL cohorts. Response duration reached 13.8 months.

The drug was well-tolerated with an acceptable toxicity profile, Dr Blum said. The most frequently reported treatment-emergent adverse events of any grade were thrombocytopenia, anemia, and neutropenia, all at 9%.

Infusion-related reactions were reported in 9% of patients and were typically grade 1 or 2. There have been no treatment-related deaths.

Protocols are being developed for trials that combine MOR208 with other anti-lymphoma therapies, with plans to open phase 1/2 trials by mid-2015.

“We plan to take the drug forward in combination with bendamustine or lenalidomide plus rituximab,” Dr Blum said. “By adding the drug into a bendamustine-rituximab combination, we will hit 2 different targets and may see synergistic cell killing.”

SAN FRANCISCO—The anti-CD19 antibody M0R208 has demonstrated encouraging single-agent activity in patients with relapsed or refractory non-Hodgkin lymphoma (NHL), according to a presenter at the 2014 ASH Annual Meeting.

“It is encouraging to see results in an NHL study that selects a different target than CD20,” said Kristie Blum, MD, of The Ohio State University in Columbus.

“In particular, it is good to see activity in elderly large-cell lymphoma patients.”

MOR208 is an Fc-engineered humanized monoclonal antibody that targets the CD19 antigen.

“It possesses significantly enhanced antibody-dependent cell-mediated cytotoxicity, a key mechanism for tumor cell killing,” Dr Blum explained. “We have seen previous responses in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL).”

In fact, MOR208 recently received fast-track designation from the US Food and Drug Administration to treat DLBCL.

At ASH, Dr Blum reported on a non-randomized, phase 2a study designed to assess the efficacy and safety of single-agent MOR208 in adults with relapsed or refractory NHL (abstract 3089). The trial was sponsored by MorphoSys AG, the company developing MOR208.

The study included 89 patients—35 with DLBCL, 31 with FL, 12 with mantle cell lymphoma (MCL), and 11 with other indolent NHLs (iNHLs). The patients had a median age of 67 years, were previously treated with rituximab, and were not candidates for high-dose therapy with stem cell support.

The patients were treated over 56 days. MOR208 was given intravenously at 12 mg/kg as 8 weekly doses on days 1, 8, 15, and 22 of each cycle. Patients with at least stable disease continued treatment for another cycle.

After completing 12 weekly doses of treatment, responding patients received maintenance MOR208 every 2 or 4 weeks, depending on the investigator’s decision, until progression.

The results showed overall response rates of 26% for DLBCL patients, 23% for FL patients, and 36% in iNHL patients. No MCL patients responded.

There were 2 complete responses in the DLBCL cohort and 1 complete response each in the FL and iNHL cohorts. Response duration reached 13.8 months.

The drug was well-tolerated with an acceptable toxicity profile, Dr Blum said. The most frequently reported treatment-emergent adverse events of any grade were thrombocytopenia, anemia, and neutropenia, all at 9%.

Infusion-related reactions were reported in 9% of patients and were typically grade 1 or 2. There have been no treatment-related deaths.

Protocols are being developed for trials that combine MOR208 with other anti-lymphoma therapies, with plans to open phase 1/2 trials by mid-2015.

“We plan to take the drug forward in combination with bendamustine or lenalidomide plus rituximab,” Dr Blum said. “By adding the drug into a bendamustine-rituximab combination, we will hit 2 different targets and may see synergistic cell killing.”

SAN FRANCISCO—The anti-CD19 antibody M0R208 has demonstrated encouraging single-agent activity in patients with relapsed or refractory non-Hodgkin lymphoma (NHL), according to a presenter at the 2014 ASH Annual Meeting.

“It is encouraging to see results in an NHL study that selects a different target than CD20,” said Kristie Blum, MD, of The Ohio State University in Columbus.

“In particular, it is good to see activity in elderly large-cell lymphoma patients.”

MOR208 is an Fc-engineered humanized monoclonal antibody that targets the CD19 antigen.

“It possesses significantly enhanced antibody-dependent cell-mediated cytotoxicity, a key mechanism for tumor cell killing,” Dr Blum explained. “We have seen previous responses in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL).”

In fact, MOR208 recently received fast-track designation from the US Food and Drug Administration to treat DLBCL.

At ASH, Dr Blum reported on a non-randomized, phase 2a study designed to assess the efficacy and safety of single-agent MOR208 in adults with relapsed or refractory NHL (abstract 3089). The trial was sponsored by MorphoSys AG, the company developing MOR208.

The study included 89 patients—35 with DLBCL, 31 with FL, 12 with mantle cell lymphoma (MCL), and 11 with other indolent NHLs (iNHLs). The patients had a median age of 67 years, were previously treated with rituximab, and were not candidates for high-dose therapy with stem cell support.

The patients were treated over 56 days. MOR208 was given intravenously at 12 mg/kg as 8 weekly doses on days 1, 8, 15, and 22 of each cycle. Patients with at least stable disease continued treatment for another cycle.

After completing 12 weekly doses of treatment, responding patients received maintenance MOR208 every 2 or 4 weeks, depending on the investigator’s decision, until progression.

The results showed overall response rates of 26% for DLBCL patients, 23% for FL patients, and 36% in iNHL patients. No MCL patients responded.

There were 2 complete responses in the DLBCL cohort and 1 complete response each in the FL and iNHL cohorts. Response duration reached 13.8 months.

The drug was well-tolerated with an acceptable toxicity profile, Dr Blum said. The most frequently reported treatment-emergent adverse events of any grade were thrombocytopenia, anemia, and neutropenia, all at 9%.

Infusion-related reactions were reported in 9% of patients and were typically grade 1 or 2. There have been no treatment-related deaths.

Protocols are being developed for trials that combine MOR208 with other anti-lymphoma therapies, with plans to open phase 1/2 trials by mid-2015.

“We plan to take the drug forward in combination with bendamustine or lenalidomide plus rituximab,” Dr Blum said. “By adding the drug into a bendamustine-rituximab combination, we will hit 2 different targets and may see synergistic cell killing.”

Attendees stop to talk at

the 2014 ASH Annual Meeting

SAN FRANCISCO—Combination therapy with ruxolitinib and panobinostat shows signs of efficacy in myelofibrosis (MF), according to research

presented at the 2014 ASH Annual Meeting.

“Targeting multiple components of the JAK/STAT pathway, as well as parallel signaling pathways that may also be involved in the pathogenesis of myelofibrosis, has the potential to have a synergistic therapeutic effect on the underlying disease,” said Jean-Jacques Kiladjian MD, PhD, of the Hôpital Saint-Louis and Université Paris Diderot in Paris, France.

Ruxolitinib, a potent JAK1/JAK2 inhibitor, demonstrated rapid and durable reductions in splenomegaly and MF-related symptoms, improved quality of life, and provided a survival advantage in the phase 3 COMFORT studies.

Panobinostat, a potent oral pan-deacetylase inhibitor, reduced spleen size, symptoms, and JAK2^V617F allele burden in patients with MF in phase 1 and phase 2 studies.

The combination of ruxolitinib and panobinostat demonstrated synergistic anti-MF activity in a phase 1b study.

At ASH, Dr Kiladjian presented updated results from the expansion phase of this trial (abstract 711). This study was sponsored by Novartis, the company developing ruxolitinib.

The treatment schedule was ruxolitinib at 5 mg to 15 mg twice daily and panobinostat at 10 mg to 25 mg once daily 3 times per week on days 2, 4, and 6 every other week in a 28-day cycle.

A dose-escalation phase included 38 patients with a median age of 63 years, and an expansion phase included 23 patients with a median age of 67 years.

The recommended phase 2 dose was 15 mg of ruxolitinib twice daily and 25 mg of panobinostat twice weekly, every other week.

“Changes in spleen size were seen in the escalation phase, even at low doses,” Dr Kiladjian said. “Some patients completely eliminated splenomegaly.”

The expansion phase showed similar results. At 24 weeks, more than 85% of patients had a 50% or greater reduction in splenomegaly. Some 59% of patients achieved a 50% or greater reduction in palpable spleen length.

“We saw some JAK2 inhibition and reduction in bone marrow fibrosis, as well as significant reduction in several cytokines related to inflammation,” Dr Kiladjian said.

The most common hematologic adverse events were anemia and thrombocytopenia. There were few neutropenias.

“We saw quite remarkably stable levels of hemoglobin and platelets,” Dr Kiladjian said.

Non-hematologic adverse events were primarily gastrointestinal toxicity associated with panobinostat, including grade 3 or 4 diarrhea and asthenia.

“The rates of adverse events observed in this trial are in line with the expected and known adverse events of these 2 agents when used as monotherapies,” Dr Kiladjian said.

“The combination of ruxolitinib and panobinostat was well-tolerated and resulted in substantial reductions in splenomegaly. Most patients treated at the [recommended phase 2 dose] of combination therapy achieved a spleen response.”

Dr Kiladjian therefore encouraged further exploration of this “favorable” combination.

Attendees stop to talk at

the 2014 ASH Annual Meeting

SAN FRANCISCO—Combination therapy with ruxolitinib and panobinostat shows signs of efficacy in myelofibrosis (MF), according to research

presented at the 2014 ASH Annual Meeting.

“Targeting multiple components of the JAK/STAT pathway, as well as parallel signaling pathways that may also be involved in the pathogenesis of myelofibrosis, has the potential to have a synergistic therapeutic effect on the underlying disease,” said Jean-Jacques Kiladjian MD, PhD, of the Hôpital Saint-Louis and Université Paris Diderot in Paris, France.

Ruxolitinib, a potent JAK1/JAK2 inhibitor, demonstrated rapid and durable reductions in splenomegaly and MF-related symptoms, improved quality of life, and provided a survival advantage in the phase 3 COMFORT studies.

Panobinostat, a potent oral pan-deacetylase inhibitor, reduced spleen size, symptoms, and JAK2^V617F allele burden in patients with MF in phase 1 and phase 2 studies.

The combination of ruxolitinib and panobinostat demonstrated synergistic anti-MF activity in a phase 1b study.

At ASH, Dr Kiladjian presented updated results from the expansion phase of this trial (abstract 711). This study was sponsored by Novartis, the company developing ruxolitinib.

The treatment schedule was ruxolitinib at 5 mg to 15 mg twice daily and panobinostat at 10 mg to 25 mg once daily 3 times per week on days 2, 4, and 6 every other week in a 28-day cycle.

A dose-escalation phase included 38 patients with a median age of 63 years, and an expansion phase included 23 patients with a median age of 67 years.

The recommended phase 2 dose was 15 mg of ruxolitinib twice daily and 25 mg of panobinostat twice weekly, every other week.

“Changes in spleen size were seen in the escalation phase, even at low doses,” Dr Kiladjian said. “Some patients completely eliminated splenomegaly.”

The expansion phase showed similar results. At 24 weeks, more than 85% of patients had a 50% or greater reduction in splenomegaly. Some 59% of patients achieved a 50% or greater reduction in palpable spleen length.

“We saw some JAK2 inhibition and reduction in bone marrow fibrosis, as well as significant reduction in several cytokines related to inflammation,” Dr Kiladjian said.

The most common hematologic adverse events were anemia and thrombocytopenia. There were few neutropenias.

“We saw quite remarkably stable levels of hemoglobin and platelets,” Dr Kiladjian said.

Non-hematologic adverse events were primarily gastrointestinal toxicity associated with panobinostat, including grade 3 or 4 diarrhea and asthenia.

“The rates of adverse events observed in this trial are in line with the expected and known adverse events of these 2 agents when used as monotherapies,” Dr Kiladjian said.

“The combination of ruxolitinib and panobinostat was well-tolerated and resulted in substantial reductions in splenomegaly. Most patients treated at the [recommended phase 2 dose] of combination therapy achieved a spleen response.”

Dr Kiladjian therefore encouraged further exploration of this “favorable” combination.

Attendees stop to talk at

the 2014 ASH Annual Meeting

SAN FRANCISCO—Combination therapy with ruxolitinib and panobinostat shows signs of efficacy in myelofibrosis (MF), according to research

presented at the 2014 ASH Annual Meeting.

“Targeting multiple components of the JAK/STAT pathway, as well as parallel signaling pathways that may also be involved in the pathogenesis of myelofibrosis, has the potential to have a synergistic therapeutic effect on the underlying disease,” said Jean-Jacques Kiladjian MD, PhD, of the Hôpital Saint-Louis and Université Paris Diderot in Paris, France.

Ruxolitinib, a potent JAK1/JAK2 inhibitor, demonstrated rapid and durable reductions in splenomegaly and MF-related symptoms, improved quality of life, and provided a survival advantage in the phase 3 COMFORT studies.

Panobinostat, a potent oral pan-deacetylase inhibitor, reduced spleen size, symptoms, and JAK2^V617F allele burden in patients with MF in phase 1 and phase 2 studies.

The combination of ruxolitinib and panobinostat demonstrated synergistic anti-MF activity in a phase 1b study.

At ASH, Dr Kiladjian presented updated results from the expansion phase of this trial (abstract 711). This study was sponsored by Novartis, the company developing ruxolitinib.

The treatment schedule was ruxolitinib at 5 mg to 15 mg twice daily and panobinostat at 10 mg to 25 mg once daily 3 times per week on days 2, 4, and 6 every other week in a 28-day cycle.

A dose-escalation phase included 38 patients with a median age of 63 years, and an expansion phase included 23 patients with a median age of 67 years.

The recommended phase 2 dose was 15 mg of ruxolitinib twice daily and 25 mg of panobinostat twice weekly, every other week.

“Changes in spleen size were seen in the escalation phase, even at low doses,” Dr Kiladjian said. “Some patients completely eliminated splenomegaly.”

The expansion phase showed similar results. At 24 weeks, more than 85% of patients had a 50% or greater reduction in splenomegaly. Some 59% of patients achieved a 50% or greater reduction in palpable spleen length.

“We saw some JAK2 inhibition and reduction in bone marrow fibrosis, as well as significant reduction in several cytokines related to inflammation,” Dr Kiladjian said.

The most common hematologic adverse events were anemia and thrombocytopenia. There were few neutropenias.

“We saw quite remarkably stable levels of hemoglobin and platelets,” Dr Kiladjian said.

Non-hematologic adverse events were primarily gastrointestinal toxicity associated with panobinostat, including grade 3 or 4 diarrhea and asthenia.

“The rates of adverse events observed in this trial are in line with the expected and known adverse events of these 2 agents when used as monotherapies,” Dr Kiladjian said.

“The combination of ruxolitinib and panobinostat was well-tolerated and resulted in substantial reductions in splenomegaly. Most patients treated at the [recommended phase 2 dose] of combination therapy achieved a spleen response.”

Dr Kiladjian therefore encouraged further exploration of this “favorable” combination.

Attendees at ASH 2014

Photo courtesy of ASH

SAN FRANCISCO—Results regarding daunorubicin escalation in induction for patients with acute myeloid leukemia (AML) have varied among different studies.

And a 90 mg/m² dose has been shown to be more effective than 45. Now, results of the UK NCRI AML17 trial have added yet another dimension to the discussion—the use of 60 mg/m² compared to 90.

Alan K. Burnett, MD, of Cardiff University in the UK, presented the data as abstract 7 at the 2014 ASH Annual Meeting.

He explained that ECOG E1900 had demonstrated superior remission and overall survival for a 90-mg dose of daunorubicin compared to a 45-mg dose in adults younger than 60.

The HOVON trial showed superior remission but no difference in overall survival for the higher dose of daunorubicin in patients older than 60.

The Korean trial demonstrated superior remission and survival rates for the 90-mg dose in patients younger than 60.

And in the GOELAMS trial, investigators found no difference between a 90-mg and a 60-mg dose level.

So the UK AML Study Group undertook to clarify the issue by comparing 90 mg to 60 mg in induction.

The investigators randomized 1206 patients younger than 60 with de novo or secondary AML or high-risk myelodysplastic syndromes (MDS) to receive 90 or 60 mg of daunorubicin on days 1, 3, and 5 of their first induction course, followed by 50 mg/m² on days 1, 3, and 5 in course 2.

All patients received ara-C during courses 1 and 2. Patients had to have LVEF of 45% or greater to be included in the trial.

The median follow-up was 29 months. Patient characteristics were comparable between the 2 groups.

The median age was 53 in both groups (range, 16-72 years), and slightly more than half of patients were male. Eighty-five percent and 84% had de novo AML in the 60-mg and 90-mg arms, respectively. Ten percent in each group had secondary AML. And 5% and 6%, respectively, had high-risk MDS.

Eleven percent in the 60-mg arm had favorable cytogenetics, compared with 9% in the 90-mg arm. Eighteen percent in each arm had mutant FLT3-ITD, and 40% in each arm were poor risk.

The investigators found no significant difference in response between the two arms—84% in the 60-mg arm and 81% in the 90-mg arm.

However, they observed a trend for increased 30-day mortality in the 90-mg arm and a significant difference in the 60-day mortality rate, which was 5% in the 60-mg arm and 10% in the 90-mg arm (P=0.001).

Twenty-nine people died by day 60 in the 60-mg arm compared with 58 in the 90-mg arm.

The main reasons for 60-day mortality in the 60-mg and 90-mg dose groups, respectively, included infection (11 vs 25 deaths), hemorrhage (3 vs 5 deaths), infection plus hemorrhage (3 vs 1 death), and resistant disease (2 vs 14 deaths), among other causes.

At 24 months, overall survival between the 2 groups was comparable, at 60% in the 60-mg arm and 59% in the 90-mg arm.

The cumulative incidence of relapse at 24 months from complete response was 41% in the 60-mg arm and 37% in the 90-mg arm.

One hundred ninety-seven patients in the 60-mg arm and 169 patients in the 90-mg arm went on to receive a stem cell transplant.

When survival was censored at transplant, there was also no difference between the arms, at 60% for the 90-mg group and 61% for the 60-mg group.

The investigators conducted subgroup analyses and found no significant benefit for 90 mg/m² in any subgroup. Dr Burnett noted, however, that there could be a potential late benefit for FLT3-ITD mutated patients who receive a 90-mg dose.

FLT3 mutated patients had a non-significant survival benefit (HR 0.74 [0.47-1.17] P=0.2) with a 90-mg dose.  However, survival was significantly worse for FLT3 wild type patients receiving 90 mg (HR 1.31 [1.03-1.67] P=0.03).

Otherwise, the group found that there is no evidence to suggest that 90 mg is superior to 60 mg.

Attendees at ASH 2014

Photo courtesy of ASH

SAN FRANCISCO—Results regarding daunorubicin escalation in induction for patients with acute myeloid leukemia (AML) have varied among different studies.

And a 90 mg/m² dose has been shown to be more effective than 45. Now, results of the UK NCRI AML17 trial have added yet another dimension to the discussion—the use of 60 mg/m² compared to 90.

Alan K. Burnett, MD, of Cardiff University in the UK, presented the data as abstract 7 at the 2014 ASH Annual Meeting.

He explained that ECOG E1900 had demonstrated superior remission and overall survival for a 90-mg dose of daunorubicin compared to a 45-mg dose in adults younger than 60.

The HOVON trial showed superior remission but no difference in overall survival for the higher dose of daunorubicin in patients older than 60.

The Korean trial demonstrated superior remission and survival rates for the 90-mg dose in patients younger than 60.

And in the GOELAMS trial, investigators found no difference between a 90-mg and a 60-mg dose level.

So the UK AML Study Group undertook to clarify the issue by comparing 90 mg to 60 mg in induction.

The investigators randomized 1206 patients younger than 60 with de novo or secondary AML or high-risk myelodysplastic syndromes (MDS) to receive 90 or 60 mg of daunorubicin on days 1, 3, and 5 of their first induction course, followed by 50 mg/m² on days 1, 3, and 5 in course 2.

All patients received ara-C during courses 1 and 2. Patients had to have LVEF of 45% or greater to be included in the trial.

The median follow-up was 29 months. Patient characteristics were comparable between the 2 groups.

The median age was 53 in both groups (range, 16-72 years), and slightly more than half of patients were male. Eighty-five percent and 84% had de novo AML in the 60-mg and 90-mg arms, respectively. Ten percent in each group had secondary AML. And 5% and 6%, respectively, had high-risk MDS.

Eleven percent in the 60-mg arm had favorable cytogenetics, compared with 9% in the 90-mg arm. Eighteen percent in each arm had mutant FLT3-ITD, and 40% in each arm were poor risk.

The investigators found no significant difference in response between the two arms—84% in the 60-mg arm and 81% in the 90-mg arm.

However, they observed a trend for increased 30-day mortality in the 90-mg arm and a significant difference in the 60-day mortality rate, which was 5% in the 60-mg arm and 10% in the 90-mg arm (P=0.001).

Twenty-nine people died by day 60 in the 60-mg arm compared with 58 in the 90-mg arm.

The main reasons for 60-day mortality in the 60-mg and 90-mg dose groups, respectively, included infection (11 vs 25 deaths), hemorrhage (3 vs 5 deaths), infection plus hemorrhage (3 vs 1 death), and resistant disease (2 vs 14 deaths), among other causes.

At 24 months, overall survival between the 2 groups was comparable, at 60% in the 60-mg arm and 59% in the 90-mg arm.

The cumulative incidence of relapse at 24 months from complete response was 41% in the 60-mg arm and 37% in the 90-mg arm.

One hundred ninety-seven patients in the 60-mg arm and 169 patients in the 90-mg arm went on to receive a stem cell transplant.

When survival was censored at transplant, there was also no difference between the arms, at 60% for the 90-mg group and 61% for the 60-mg group.

The investigators conducted subgroup analyses and found no significant benefit for 90 mg/m² in any subgroup. Dr Burnett noted, however, that there could be a potential late benefit for FLT3-ITD mutated patients who receive a 90-mg dose.

FLT3 mutated patients had a non-significant survival benefit (HR 0.74 [0.47-1.17] P=0.2) with a 90-mg dose.  However, survival was significantly worse for FLT3 wild type patients receiving 90 mg (HR 1.31 [1.03-1.67] P=0.03).

Otherwise, the group found that there is no evidence to suggest that 90 mg is superior to 60 mg.

Attendees at ASH 2014

Photo courtesy of ASH

SAN FRANCISCO—Results regarding daunorubicin escalation in induction for patients with acute myeloid leukemia (AML) have varied among different studies.

And a 90 mg/m² dose has been shown to be more effective than 45. Now, results of the UK NCRI AML17 trial have added yet another dimension to the discussion—the use of 60 mg/m² compared to 90.

Alan K. Burnett, MD, of Cardiff University in the UK, presented the data as abstract 7 at the 2014 ASH Annual Meeting.

He explained that ECOG E1900 had demonstrated superior remission and overall survival for a 90-mg dose of daunorubicin compared to a 45-mg dose in adults younger than 60.

The HOVON trial showed superior remission but no difference in overall survival for the higher dose of daunorubicin in patients older than 60.

The Korean trial demonstrated superior remission and survival rates for the 90-mg dose in patients younger than 60.

And in the GOELAMS trial, investigators found no difference between a 90-mg and a 60-mg dose level.

So the UK AML Study Group undertook to clarify the issue by comparing 90 mg to 60 mg in induction.

The investigators randomized 1206 patients younger than 60 with de novo or secondary AML or high-risk myelodysplastic syndromes (MDS) to receive 90 or 60 mg of daunorubicin on days 1, 3, and 5 of their first induction course, followed by 50 mg/m² on days 1, 3, and 5 in course 2.

All patients received ara-C during courses 1 and 2. Patients had to have LVEF of 45% or greater to be included in the trial.

The median follow-up was 29 months. Patient characteristics were comparable between the 2 groups.

The median age was 53 in both groups (range, 16-72 years), and slightly more than half of patients were male. Eighty-five percent and 84% had de novo AML in the 60-mg and 90-mg arms, respectively. Ten percent in each group had secondary AML. And 5% and 6%, respectively, had high-risk MDS.

Eleven percent in the 60-mg arm had favorable cytogenetics, compared with 9% in the 90-mg arm. Eighteen percent in each arm had mutant FLT3-ITD, and 40% in each arm were poor risk.

The investigators found no significant difference in response between the two arms—84% in the 60-mg arm and 81% in the 90-mg arm.

However, they observed a trend for increased 30-day mortality in the 90-mg arm and a significant difference in the 60-day mortality rate, which was 5% in the 60-mg arm and 10% in the 90-mg arm (P=0.001).

Twenty-nine people died by day 60 in the 60-mg arm compared with 58 in the 90-mg arm.

The main reasons for 60-day mortality in the 60-mg and 90-mg dose groups, respectively, included infection (11 vs 25 deaths), hemorrhage (3 vs 5 deaths), infection plus hemorrhage (3 vs 1 death), and resistant disease (2 vs 14 deaths), among other causes.

At 24 months, overall survival between the 2 groups was comparable, at 60% in the 60-mg arm and 59% in the 90-mg arm.

The cumulative incidence of relapse at 24 months from complete response was 41% in the 60-mg arm and 37% in the 90-mg arm.

One hundred ninety-seven patients in the 60-mg arm and 169 patients in the 90-mg arm went on to receive a stem cell transplant.

When survival was censored at transplant, there was also no difference between the arms, at 60% for the 90-mg group and 61% for the 60-mg group.

The investigators conducted subgroup analyses and found no significant benefit for 90 mg/m² in any subgroup. Dr Burnett noted, however, that there could be a potential late benefit for FLT3-ITD mutated patients who receive a 90-mg dose.

FLT3 mutated patients had a non-significant survival benefit (HR 0.74 [0.47-1.17] P=0.2) with a 90-mg dose.  However, survival was significantly worse for FLT3 wild type patients receiving 90 mg (HR 1.31 [1.03-1.67] P=0.03).

Otherwise, the group found that there is no evidence to suggest that 90 mg is superior to 60 mg.

Pills

Credit: FDA

SAN FRANCISCO—A BCL2 inhibitor that previously proved active against chronic lymphocytic leukemia has shown activity in certain patients with acute myelogenous leukemia (AML) as well.

This phase 2 trial was the first use of the inhibitor, ABT-199 (or venetoclax), in patients with relapsed or refractory AML.

Five of 32 patients treated with ABT-199 achieved a complete response (CR) or CR with incomplete blood count recovery (CRi), and several more had stable disease.

The drug appeared to be particularly active in patients with IDH mutations.

Marina Konopleva, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston, presented these results at the 2014 ASH Annual Meeting (abstract 118). The research was funded by AbbVie, Inc., the company developing ABT-199.

The trial was launched on the basis of preclinical studies showing that ABT-199 could kill AML cell lines, patients’ AML cells, and patient-derived AML cells implanted in mice.

The researchers enrolled 32 AML patients, 30 of whom had relapsed or refractory disease. Patients had a median age of 71 (range, 19 to 84), and half were male.

The overall response rate was 15.5%, with 1 patient achieving a CR and 4 patients achieving a CRi. The researchers noted that 3 of the patients who had a CR/CRi had IDH mutations. Two of these patients also achieved minimal residual disease negativity.

The team said these results suggest single-agent ABT-199 can have considerable clinical activity in patients with relapsed or refractory AML, and patients with mutations in IDH genes may be particularly sensitive to the drug.

The researchers also found the median bone marrow blast count in evaluable patients decreased 36% after treatment with ABT-199. And 6 patients (19%) had at least a 50% reduction in bone marrow blasts.

Common adverse events following treatment (occurring in at least 25% of patients) included nausea, diarrhea, fatigue, neutropenia, and vomiting. Grade 3 and 4 adverse events (occurring in 3 or more patients) included febrile neutropenia, anemia, and pneumonia.

No patients died as a result of treatment-related adverse events.

Furthermore, the maximum-tolerated dose was not reached, leaving open the possibility of higher doses in further trials. The next step is to carry out trials combining ABT-199 with other agents. These trials are currently opening at several sites.

AbbVie said ABT-199 will be studied in combination with common AML treatments, and the company is developing ABT-199 for, and evaluating the drug in, several hematologic malignancies.

Pills

Credit: FDA

SAN FRANCISCO—A BCL2 inhibitor that previously proved active against chronic lymphocytic leukemia has shown activity in certain patients with acute myelogenous leukemia (AML) as well.

This phase 2 trial was the first use of the inhibitor, ABT-199 (or venetoclax), in patients with relapsed or refractory AML.

Five of 32 patients treated with ABT-199 achieved a complete response (CR) or CR with incomplete blood count recovery (CRi), and several more had stable disease.

The drug appeared to be particularly active in patients with IDH mutations.

Marina Konopleva, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston, presented these results at the 2014 ASH Annual Meeting (abstract 118). The research was funded by AbbVie, Inc., the company developing ABT-199.

The trial was launched on the basis of preclinical studies showing that ABT-199 could kill AML cell lines, patients’ AML cells, and patient-derived AML cells implanted in mice.

The researchers enrolled 32 AML patients, 30 of whom had relapsed or refractory disease. Patients had a median age of 71 (range, 19 to 84), and half were male.

The overall response rate was 15.5%, with 1 patient achieving a CR and 4 patients achieving a CRi. The researchers noted that 3 of the patients who had a CR/CRi had IDH mutations. Two of these patients also achieved minimal residual disease negativity.

The team said these results suggest single-agent ABT-199 can have considerable clinical activity in patients with relapsed or refractory AML, and patients with mutations in IDH genes may be particularly sensitive to the drug.

The researchers also found the median bone marrow blast count in evaluable patients decreased 36% after treatment with ABT-199. And 6 patients (19%) had at least a 50% reduction in bone marrow blasts.

Common adverse events following treatment (occurring in at least 25% of patients) included nausea, diarrhea, fatigue, neutropenia, and vomiting. Grade 3 and 4 adverse events (occurring in 3 or more patients) included febrile neutropenia, anemia, and pneumonia.

No patients died as a result of treatment-related adverse events.

Furthermore, the maximum-tolerated dose was not reached, leaving open the possibility of higher doses in further trials. The next step is to carry out trials combining ABT-199 with other agents. These trials are currently opening at several sites.

AbbVie said ABT-199 will be studied in combination with common AML treatments, and the company is developing ABT-199 for, and evaluating the drug in, several hematologic malignancies.

Pills

Credit: FDA

SAN FRANCISCO—A BCL2 inhibitor that previously proved active against chronic lymphocytic leukemia has shown activity in certain patients with acute myelogenous leukemia (AML) as well.

This phase 2 trial was the first use of the inhibitor, ABT-199 (or venetoclax), in patients with relapsed or refractory AML.

Five of 32 patients treated with ABT-199 achieved a complete response (CR) or CR with incomplete blood count recovery (CRi), and several more had stable disease.

The drug appeared to be particularly active in patients with IDH mutations.

Marina Konopleva, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston, presented these results at the 2014 ASH Annual Meeting (abstract 118). The research was funded by AbbVie, Inc., the company developing ABT-199.

The trial was launched on the basis of preclinical studies showing that ABT-199 could kill AML cell lines, patients’ AML cells, and patient-derived AML cells implanted in mice.

The researchers enrolled 32 AML patients, 30 of whom had relapsed or refractory disease. Patients had a median age of 71 (range, 19 to 84), and half were male.

The overall response rate was 15.5%, with 1 patient achieving a CR and 4 patients achieving a CRi. The researchers noted that 3 of the patients who had a CR/CRi had IDH mutations. Two of these patients also achieved minimal residual disease negativity.

The team said these results suggest single-agent ABT-199 can have considerable clinical activity in patients with relapsed or refractory AML, and patients with mutations in IDH genes may be particularly sensitive to the drug.

The researchers also found the median bone marrow blast count in evaluable patients decreased 36% after treatment with ABT-199. And 6 patients (19%) had at least a 50% reduction in bone marrow blasts.

Common adverse events following treatment (occurring in at least 25% of patients) included nausea, diarrhea, fatigue, neutropenia, and vomiting. Grade 3 and 4 adverse events (occurring in 3 or more patients) included febrile neutropenia, anemia, and pneumonia.

No patients died as a result of treatment-related adverse events.

Furthermore, the maximum-tolerated dose was not reached, leaving open the possibility of higher doses in further trials. The next step is to carry out trials combining ABT-199 with other agents. These trials are currently opening at several sites.

AbbVie said ABT-199 will be studied in combination with common AML treatments, and the company is developing ABT-199 for, and evaluating the drug in, several hematologic malignancies.

SAN FRANCISCO – A first-in-class investigational agent called sotatercept appears to be safe and to improve hematologic parameters in patients with lower-risk myelodysplastic syndrome or nonproliferative chronic myelomonocytic leukemia and anemia requiring transfusion, a study showed.

In the open-label phase II dose-finding study of sotatercept in patients with myelodysplastic syndrome (MDS) or nonproliferative chronic myelomonocytic leukemia (CMML), hematologic improvement according to International Working Group (IWG) 2006 criteria was seen in 24 of 53 evaluable patients, said Dr. Rami Komrokji of the Moffitt Cancer Center,Tampa.

The patients were all refractory to, or were deemed to have a low chance of responding to, an erythropoiesis-stimulating agent (ESA), Dr. Komrokji said at the annual meeting of the American Society of Hematology.

Neil Osterweil/Frontline Medical News

“A medication like sotatercept would probably have a role in the management of anemia in lower-risk MDS patients. The treatment is administered every 3 weeks, which makes it also logistically easier for the patients to get the treatment. I don’t think we have seen any safety concern, at least at this point, about the chronic use of this medication,” he said in an interview.

Sotatercept (ACE-011) is an activin type IIA receptor fusion protein that acts on late-stage erythropoiesis to increase the release of mature erythrocytes into circulation. The mechanism of action is distinct from that of erythropoietins such as epoetin alfa (Procrit, Epogen) or darbapoietin alfa (Aranesp).

In clinical trials with healthy volunteers, sotatercept has been shown to increase hemoglobin levels, suggesting that it could help to reduce anemia and perhaps lessen dependence on transfusions among patients with lower-risk MDS, Dr. Komrokji said.

He and his colleagues at centers in the United States and France enrolled patients with low-risk or intermediate-1–risk MDS as defined by the International Prognostic Scoring System (IPSS), or nonproliferative CMML (fewer than 13,000 white blood cells per microliter). The patients had to have anemia requiring at least 2 red blood cell (RBC) transfusions in the 12 weeks before enrollment for hemoglobin levels below 9.0 g/dL, and no response, loss of response, or a low chance of response to an ESA. Those patients with serum erythropoietin levels greater than 500 mIU/mL were considered to have a low chance of responding to an ESA.

The patients received subcutaneous injections of sotatercept at doses of 0.1, 0.3, 0.5, or 1.0 mg/kg once every 3 weeks.

As noted, the rate of overall hematologic improvement by IWG 2006 criteria was 45%, occurring in 24 of 53 patients available for evaluation. Five of 44 patients with a high transfusion burden (4 or more RBC units required within 8 weeks) were able to be free of RBC transfusions for at least 8 weeks, as were 5 of 9 with a low transfusion burden (fewer than 4 RBC units over a period of 8 weeks).

Looking at the efficacy in patients with a high transfusion burden, the investigators found that 4 of 6 assigned to the 0.3-mg/kg dose group and 8 of 14 assigned to the 1-mg/kg dose group had a reduction in transfusion burden. The median duration of effect was 106 days, with the longest response lasting for 150 days.

There were no major adverse events in the study, and no apparent increase in risk for thrombosis, as had been seen in some studies of ESAs. Another theoretical risk with this type of agent is hypertension, but there was only one grade 3 case and no grade 4 cases of hypertension in the study, Dr. Komrokji said.

Sotatercept is currently in phase II trials for anemia related to hematologic malignancies and other diseases.

SAN FRANCISCO – A first-in-class investigational agent called sotatercept appears to be safe and to improve hematologic parameters in patients with lower-risk myelodysplastic syndrome or nonproliferative chronic myelomonocytic leukemia and anemia requiring transfusion, a study showed.

In the open-label phase II dose-finding study of sotatercept in patients with myelodysplastic syndrome (MDS) or nonproliferative chronic myelomonocytic leukemia (CMML), hematologic improvement according to International Working Group (IWG) 2006 criteria was seen in 24 of 53 evaluable patients, said Dr. Rami Komrokji of the Moffitt Cancer Center,Tampa.

The patients were all refractory to, or were deemed to have a low chance of responding to, an erythropoiesis-stimulating agent (ESA), Dr. Komrokji said at the annual meeting of the American Society of Hematology.

Neil Osterweil/Frontline Medical News

“A medication like sotatercept would probably have a role in the management of anemia in lower-risk MDS patients. The treatment is administered every 3 weeks, which makes it also logistically easier for the patients to get the treatment. I don’t think we have seen any safety concern, at least at this point, about the chronic use of this medication,” he said in an interview.

Sotatercept (ACE-011) is an activin type IIA receptor fusion protein that acts on late-stage erythropoiesis to increase the release of mature erythrocytes into circulation. The mechanism of action is distinct from that of erythropoietins such as epoetin alfa (Procrit, Epogen) or darbapoietin alfa (Aranesp).

In clinical trials with healthy volunteers, sotatercept has been shown to increase hemoglobin levels, suggesting that it could help to reduce anemia and perhaps lessen dependence on transfusions among patients with lower-risk MDS, Dr. Komrokji said.

He and his colleagues at centers in the United States and France enrolled patients with low-risk or intermediate-1–risk MDS as defined by the International Prognostic Scoring System (IPSS), or nonproliferative CMML (fewer than 13,000 white blood cells per microliter). The patients had to have anemia requiring at least 2 red blood cell (RBC) transfusions in the 12 weeks before enrollment for hemoglobin levels below 9.0 g/dL, and no response, loss of response, or a low chance of response to an ESA. Those patients with serum erythropoietin levels greater than 500 mIU/mL were considered to have a low chance of responding to an ESA.

The patients received subcutaneous injections of sotatercept at doses of 0.1, 0.3, 0.5, or 1.0 mg/kg once every 3 weeks.

As noted, the rate of overall hematologic improvement by IWG 2006 criteria was 45%, occurring in 24 of 53 patients available for evaluation. Five of 44 patients with a high transfusion burden (4 or more RBC units required within 8 weeks) were able to be free of RBC transfusions for at least 8 weeks, as were 5 of 9 with a low transfusion burden (fewer than 4 RBC units over a period of 8 weeks).

Looking at the efficacy in patients with a high transfusion burden, the investigators found that 4 of 6 assigned to the 0.3-mg/kg dose group and 8 of 14 assigned to the 1-mg/kg dose group had a reduction in transfusion burden. The median duration of effect was 106 days, with the longest response lasting for 150 days.

There were no major adverse events in the study, and no apparent increase in risk for thrombosis, as had been seen in some studies of ESAs. Another theoretical risk with this type of agent is hypertension, but there was only one grade 3 case and no grade 4 cases of hypertension in the study, Dr. Komrokji said.

Sotatercept is currently in phase II trials for anemia related to hematologic malignancies and other diseases.

SAN FRANCISCO – A first-in-class investigational agent called sotatercept appears to be safe and to improve hematologic parameters in patients with lower-risk myelodysplastic syndrome or nonproliferative chronic myelomonocytic leukemia and anemia requiring transfusion, a study showed.

In the open-label phase II dose-finding study of sotatercept in patients with myelodysplastic syndrome (MDS) or nonproliferative chronic myelomonocytic leukemia (CMML), hematologic improvement according to International Working Group (IWG) 2006 criteria was seen in 24 of 53 evaluable patients, said Dr. Rami Komrokji of the Moffitt Cancer Center,Tampa.

The patients were all refractory to, or were deemed to have a low chance of responding to, an erythropoiesis-stimulating agent (ESA), Dr. Komrokji said at the annual meeting of the American Society of Hematology.

Neil Osterweil/Frontline Medical News

“A medication like sotatercept would probably have a role in the management of anemia in lower-risk MDS patients. The treatment is administered every 3 weeks, which makes it also logistically easier for the patients to get the treatment. I don’t think we have seen any safety concern, at least at this point, about the chronic use of this medication,” he said in an interview.

Sotatercept (ACE-011) is an activin type IIA receptor fusion protein that acts on late-stage erythropoiesis to increase the release of mature erythrocytes into circulation. The mechanism of action is distinct from that of erythropoietins such as epoetin alfa (Procrit, Epogen) or darbapoietin alfa (Aranesp).

In clinical trials with healthy volunteers, sotatercept has been shown to increase hemoglobin levels, suggesting that it could help to reduce anemia and perhaps lessen dependence on transfusions among patients with lower-risk MDS, Dr. Komrokji said.

He and his colleagues at centers in the United States and France enrolled patients with low-risk or intermediate-1–risk MDS as defined by the International Prognostic Scoring System (IPSS), or nonproliferative CMML (fewer than 13,000 white blood cells per microliter). The patients had to have anemia requiring at least 2 red blood cell (RBC) transfusions in the 12 weeks before enrollment for hemoglobin levels below 9.0 g/dL, and no response, loss of response, or a low chance of response to an ESA. Those patients with serum erythropoietin levels greater than 500 mIU/mL were considered to have a low chance of responding to an ESA.

The patients received subcutaneous injections of sotatercept at doses of 0.1, 0.3, 0.5, or 1.0 mg/kg once every 3 weeks.

As noted, the rate of overall hematologic improvement by IWG 2006 criteria was 45%, occurring in 24 of 53 patients available for evaluation. Five of 44 patients with a high transfusion burden (4 or more RBC units required within 8 weeks) were able to be free of RBC transfusions for at least 8 weeks, as were 5 of 9 with a low transfusion burden (fewer than 4 RBC units over a period of 8 weeks).

Looking at the efficacy in patients with a high transfusion burden, the investigators found that 4 of 6 assigned to the 0.3-mg/kg dose group and 8 of 14 assigned to the 1-mg/kg dose group had a reduction in transfusion burden. The median duration of effect was 106 days, with the longest response lasting for 150 days.

There were no major adverse events in the study, and no apparent increase in risk for thrombosis, as had been seen in some studies of ESAs. Another theoretical risk with this type of agent is hypertension, but there was only one grade 3 case and no grade 4 cases of hypertension in the study, Dr. Komrokji said.

Sotatercept is currently in phase II trials for anemia related to hematologic malignancies and other diseases.

SAN FRANCISCO– The study was small but encouraging: Among 47 older patients with newly diagnosed acute lymphoblastic leukemia positive for the Philadelphia chromosome, 41 had a complete hematologic response to a combination of chemotherapy and the targeted agent nilotinib (Tasigna), report investigators from a European consortium.

“The data I have presented show that the combination of nilotinib with this age-adapted chemotherapy is highly effective. We do have quite a reasonable overall survival estimate at 2 years of just more than 70%,” said Dr. Oliver Ottmann of Goethe University in Frankfurt, on behalf of colleagues in the European Working Group for Adult ALL (EWALL).

The study also shows that although some centers are reluctant to offer allogeneic stem cell transplantation (SCT) to older patients, it is still a viable treatment option in this population, Dr. Ottmann said at a briefing at the annual meeting of the American Society of Hematology.

Although older patients with newly diagnosed Philadelphia-positive (Ph+) ALL have a high complete hematologic response rate (CHR) with imatinib (Gleevec), they generally have a poor prognosis because of a high rate of relapse.

Because nilotinib, a potent inhibitor of the ABL kinase, has good efficacy in the chronic and accelerated phase of Ph+ chronic myeloid leukemia, the EWALL investigators initiated a study to evaluate it in combination with chemotherapy in the front-line setting.

Adults aged 55 years and older with ALL positive for the Philadelphia chromosome and/or BCR-ABL1 fusion who were treatment naive or had not received therapy other than corticosteroids, single-dose vincristine, or three doses of cyclophosphamide were eligible.

Details of the combination regimen are available online.

Briefly, following a prephase with dexamethasone and optional cyclophosphamide, patients receive nilotinib 400 mg twice daily starting with induction and continuously thereafter. During induction, nilotinib is given with intravenous injections of vincristine and dexamethasone for 4 weeks, followed by consolidation with nilotinib, methotrexate, asparaginase and cytarabine. Maintenance consists of nilotinib, 6-mercaptopurine, and methotrexate once weekly for 1 month then every other month, and dexamethasone and vincristine in 2 month intervals up to 24 months.

The data Dr. Ottmann reported come from an interim analysis of the ongoing study. As of August 2014, data on 47 of 56 patients was available for an efficacy analysis, As noted before, the rate of CHR was 87%, occurring in 41 of 47 patients. The treatment evoked a partial response or no response in 2 patients, and there was one death during the induction phase. Additionally, three patients discontinued therapy early and were not included in the assessment, but at least one had a complete response later on, Dr. Ottmann noted.

The median time to a complete response (CR) was 41 days, but CRs occurred as early as 25 days and as late as 62 days after the start of therapy. The remissions at the time of data cutoff appeared to be durable, but follow-up is still early, he said.

Overall survival at a median follow-up for all patients of 8.6 months was 72.7% at 30 months for patients who did not undergo SCT (allowed under the protocol), and 67.1% at 30 months for patients who underwent SCT. This difference was not significant, but only nine patients at the time of data cutoff had undergone transplantation.

“It will be interesting to see how this will proceed if the transplant-free patients will do as well as the others,” Dr. Ottmann said.

An analysis of molecular response by minimal residual disease (MRD) time point showed a significant further increase with the consolidation chemotherapy and kinase inhibitor, emphasizing that “continuing the treatment in this form emphasizes the depth of response. If we then look at the rate of MRD negativity using high quality assays, then a quarter of the patients have undetectable polymerase chain reaction during the consolidation cycles, and approximately 80% achieves something that we call a major molecular response,” he said.

Dr. Ottmann did not provide updated safety data, but at the time of the data cutoff, there had been 34 serious adverse events reported, 11 of which occurred during induction, 16 during consolidation, 6 during maintenance, and 1 following discontinuation. The most-common adverse events were infections and neutropenic fevers. Single serious adverse events included metabolic, cardiovascular, neurologic, renal, and hepatic events.

The trial is expected to be completed in the next few months.

SAN FRANCISCO– The study was small but encouraging: Among 47 older patients with newly diagnosed acute lymphoblastic leukemia positive for the Philadelphia chromosome, 41 had a complete hematologic response to a combination of chemotherapy and the targeted agent nilotinib (Tasigna), report investigators from a European consortium.

“The data I have presented show that the combination of nilotinib with this age-adapted chemotherapy is highly effective. We do have quite a reasonable overall survival estimate at 2 years of just more than 70%,” said Dr. Oliver Ottmann of Goethe University in Frankfurt, on behalf of colleagues in the European Working Group for Adult ALL (EWALL).

The study also shows that although some centers are reluctant to offer allogeneic stem cell transplantation (SCT) to older patients, it is still a viable treatment option in this population, Dr. Ottmann said at a briefing at the annual meeting of the American Society of Hematology.

Although older patients with newly diagnosed Philadelphia-positive (Ph+) ALL have a high complete hematologic response rate (CHR) with imatinib (Gleevec), they generally have a poor prognosis because of a high rate of relapse.

Because nilotinib, a potent inhibitor of the ABL kinase, has good efficacy in the chronic and accelerated phase of Ph+ chronic myeloid leukemia, the EWALL investigators initiated a study to evaluate it in combination with chemotherapy in the front-line setting.

Adults aged 55 years and older with ALL positive for the Philadelphia chromosome and/or BCR-ABL1 fusion who were treatment naive or had not received therapy other than corticosteroids, single-dose vincristine, or three doses of cyclophosphamide were eligible.

Details of the combination regimen are available online.

Briefly, following a prephase with dexamethasone and optional cyclophosphamide, patients receive nilotinib 400 mg twice daily starting with induction and continuously thereafter. During induction, nilotinib is given with intravenous injections of vincristine and dexamethasone for 4 weeks, followed by consolidation with nilotinib, methotrexate, asparaginase and cytarabine. Maintenance consists of nilotinib, 6-mercaptopurine, and methotrexate once weekly for 1 month then every other month, and dexamethasone and vincristine in 2 month intervals up to 24 months.

The data Dr. Ottmann reported come from an interim analysis of the ongoing study. As of August 2014, data on 47 of 56 patients was available for an efficacy analysis, As noted before, the rate of CHR was 87%, occurring in 41 of 47 patients. The treatment evoked a partial response or no response in 2 patients, and there was one death during the induction phase. Additionally, three patients discontinued therapy early and were not included in the assessment, but at least one had a complete response later on, Dr. Ottmann noted.

The median time to a complete response (CR) was 41 days, but CRs occurred as early as 25 days and as late as 62 days after the start of therapy. The remissions at the time of data cutoff appeared to be durable, but follow-up is still early, he said.

Overall survival at a median follow-up for all patients of 8.6 months was 72.7% at 30 months for patients who did not undergo SCT (allowed under the protocol), and 67.1% at 30 months for patients who underwent SCT. This difference was not significant, but only nine patients at the time of data cutoff had undergone transplantation.

“It will be interesting to see how this will proceed if the transplant-free patients will do as well as the others,” Dr. Ottmann said.

An analysis of molecular response by minimal residual disease (MRD) time point showed a significant further increase with the consolidation chemotherapy and kinase inhibitor, emphasizing that “continuing the treatment in this form emphasizes the depth of response. If we then look at the rate of MRD negativity using high quality assays, then a quarter of the patients have undetectable polymerase chain reaction during the consolidation cycles, and approximately 80% achieves something that we call a major molecular response,” he said.

Dr. Ottmann did not provide updated safety data, but at the time of the data cutoff, there had been 34 serious adverse events reported, 11 of which occurred during induction, 16 during consolidation, 6 during maintenance, and 1 following discontinuation. The most-common adverse events were infections and neutropenic fevers. Single serious adverse events included metabolic, cardiovascular, neurologic, renal, and hepatic events.

The trial is expected to be completed in the next few months.

SAN FRANCISCO– The study was small but encouraging: Among 47 older patients with newly diagnosed acute lymphoblastic leukemia positive for the Philadelphia chromosome, 41 had a complete hematologic response to a combination of chemotherapy and the targeted agent nilotinib (Tasigna), report investigators from a European consortium.

“The data I have presented show that the combination of nilotinib with this age-adapted chemotherapy is highly effective. We do have quite a reasonable overall survival estimate at 2 years of just more than 70%,” said Dr. Oliver Ottmann of Goethe University in Frankfurt, on behalf of colleagues in the European Working Group for Adult ALL (EWALL).

The study also shows that although some centers are reluctant to offer allogeneic stem cell transplantation (SCT) to older patients, it is still a viable treatment option in this population, Dr. Ottmann said at a briefing at the annual meeting of the American Society of Hematology.

Although older patients with newly diagnosed Philadelphia-positive (Ph+) ALL have a high complete hematologic response rate (CHR) with imatinib (Gleevec), they generally have a poor prognosis because of a high rate of relapse.

Because nilotinib, a potent inhibitor of the ABL kinase, has good efficacy in the chronic and accelerated phase of Ph+ chronic myeloid leukemia, the EWALL investigators initiated a study to evaluate it in combination with chemotherapy in the front-line setting.

Adults aged 55 years and older with ALL positive for the Philadelphia chromosome and/or BCR-ABL1 fusion who were treatment naive or had not received therapy other than corticosteroids, single-dose vincristine, or three doses of cyclophosphamide were eligible.

Details of the combination regimen are available online.

Briefly, following a prephase with dexamethasone and optional cyclophosphamide, patients receive nilotinib 400 mg twice daily starting with induction and continuously thereafter. During induction, nilotinib is given with intravenous injections of vincristine and dexamethasone for 4 weeks, followed by consolidation with nilotinib, methotrexate, asparaginase and cytarabine. Maintenance consists of nilotinib, 6-mercaptopurine, and methotrexate once weekly for 1 month then every other month, and dexamethasone and vincristine in 2 month intervals up to 24 months.

The data Dr. Ottmann reported come from an interim analysis of the ongoing study. As of August 2014, data on 47 of 56 patients was available for an efficacy analysis, As noted before, the rate of CHR was 87%, occurring in 41 of 47 patients. The treatment evoked a partial response or no response in 2 patients, and there was one death during the induction phase. Additionally, three patients discontinued therapy early and were not included in the assessment, but at least one had a complete response later on, Dr. Ottmann noted.

The median time to a complete response (CR) was 41 days, but CRs occurred as early as 25 days and as late as 62 days after the start of therapy. The remissions at the time of data cutoff appeared to be durable, but follow-up is still early, he said.

Overall survival at a median follow-up for all patients of 8.6 months was 72.7% at 30 months for patients who did not undergo SCT (allowed under the protocol), and 67.1% at 30 months for patients who underwent SCT. This difference was not significant, but only nine patients at the time of data cutoff had undergone transplantation.

“It will be interesting to see how this will proceed if the transplant-free patients will do as well as the others,” Dr. Ottmann said.

An analysis of molecular response by minimal residual disease (MRD) time point showed a significant further increase with the consolidation chemotherapy and kinase inhibitor, emphasizing that “continuing the treatment in this form emphasizes the depth of response. If we then look at the rate of MRD negativity using high quality assays, then a quarter of the patients have undetectable polymerase chain reaction during the consolidation cycles, and approximately 80% achieves something that we call a major molecular response,” he said.

Dr. Ottmann did not provide updated safety data, but at the time of the data cutoff, there had been 34 serious adverse events reported, 11 of which occurred during induction, 16 during consolidation, 6 during maintenance, and 1 following discontinuation. The most-common adverse events were infections and neutropenic fevers. Single serious adverse events included metabolic, cardiovascular, neurologic, renal, and hepatic events.

The trial is expected to be completed in the next few months.

SAN FRANCISCO—Administering brentuximab vedotin immediately after autologous stem cell transplant can improve progression-free survival (PFS) in patients with Hodgkin lymphoma (HL), results of the phase 3 AETHERA trial suggest.

The overall survival (OS) data for this study are not yet mature, but the significant improvement in PFS will likely translate to improved OS in a few years’ time, according to Craig Moskowitz, MD, of Memorial Sloan Kettering Cancer Center in New York.

Dr Moskowitz presented results from the AETHERA trial at the 2014 ASH Annual Meeting as abstract 673. The trial was funded by Seattle Genetics, Inc., and Takeda Pharmaceutical Company Limited, the companies developing brentuximab.

The trial included HL patients with at least one risk factor for progression. Eligible patients must have had a history of refractory HL, relapsed within a year of receiving frontline chemotherapy, and/or had disease outside of the lymph nodes at the time of pre-transplant relapse.

Researchers enrolled 329 patients, and they were randomized to receive brentuximab or placebo every 3 weeks for up to about a year. Baseline characteristics were similar between the 2 arms.

Dr Moskowitz pointed out that 43% of patients in the brentuximab arm and 48% in the placebo arm had required 2 or more prior salvage therapies, and 60% and 59%, respectively, had primary refractory HL.

Patients in both arms received a median of 15 treatment cycles, with an average of 12 cycles on the brentuximab arm and 11 cycles on the placebo arm.

“Patients who progressed in the placebo arm could be unblinded and subsequently receive brentuximab on a companion study,” Dr Moskowitz noted. “So technically, this was a cross-over design, making overall survival at 24 months quite unlikely.”

Efficacy/survival results

About half of patients in each arm completed treatment—47% in the brentuximab arm and 49% in the placebo arm. The reasons for discontinuation included disease progression (15% and 42%, respectively), adverse events (33% and 6%, respectively), and patient decision (5% and 2%, respectively).

Still, the trial achieved its primary endpoint, demonstrating a significant increase in PFS, according to an independent review facility (IRF).

The median PFS per the IRF was 43 months for patients in the brentuximab arm and 24 months in the placebo arm (hazard ratio=0.57, P=0.001). The 2-year PFS rates per the IRF were 63% and 51%, respectively.

The 2-year PFS rate according to investigators was 65% in the brentuximab arm and 45% in the placebo arm. The median PFS per investigators has not yet been reached for brentuximab but was 16 months for placebo.

The PFS benefit was consistent across all pre-specified subgroups, Dr Moskowitz noted, including primary refractory patients, patients who relapsed within 12 months of frontline therapy, and patients who relapsed after 12 months with extranodal disease.

Patients who experienced disease progression received a variety of subsequent therapies.

In the brentuximab arm, 16% of patients receiving subsequent therapy were treated with brentuximab after relapse. In the placebo arm, 85% of patients receiving subsequent therapy were treated with single-agent brentuximab.

Twenty-eight percent of patients in the placebo arm and 25% in the brentuximab arm received stem cell transplant as subsequent therapy, the majority of which were allogeneic transplants. Dr Moskowitz said a second transplant could have improved survival in these patients, but whether it actually did is unclear.

He noted that the OS data are immature, but there is currently no significant difference in OS between the treatment arms (hazard ratio=1.15; P=0.62).

“The median follow-up right now is 24 months,” he said. “So one will have to wait for a survival advantage or disadvantage, but from my point of view, a PFS of 65% at 2 years will translate to an overall survival difference. We’re just going to have to wait a few more years.”

Dr Moskowitz said another analysis of OS is planned in 2016.

Safety data

The most common adverse events in the brentuximab arm were peripheral sensory neuropathy (56%), neutropenia (35%), upper respiratory tract infection (26%), fatigue (24%), and peripheral motor neuropathy (23%).

The most common adverse events in the placebo arm were upper respiratory tract infection (23%), fatigue (18%), peripheral sensory neuropathy (16%), cough (16%), and neutropenia (12%).

Eighty-five percent of patients with peripheral neuropathy in the brentuximab arm had a resolution or improvement in symptoms, with a median time to improvement of 23.4 weeks.

Grade 3 or higher adverse events in the brentuximab arm included neutropenia, peripheral sensory neuropathy, peripheral motor neuropathy, nausea, fatigue, and diarrhea.

Grade 3 or higher adverse events in the placebo arm included neutropenia, fatigue, peripheral motor neuropathy, diarrhea, and peripheral sensory neuropathy. No Grade 4 peripheral neuropathy events occurred.

One death occurred within 30 days of brentuximab treatment. The patient died from treatment-related acute respiratory distress syndrome (ARDS) associated with pneumonitis.

Another death occurred on the brentuximab arm at day 40 from ARDS following an episode of treatment-related acute pancreatitis, which had resolved at the time of death.

Nevertheless, Dr Moskowitz characterized brentuximab consolidation as “very well-tolerated” in this patient population.

He concluded, “For patients with a remission duration of less than a year, patients with primary refractory Hodgkin lymphoma, and patients with Hodgkin lymphoma with extranodal involvement, I do believe this will become standard treatment.”

SAN FRANCISCO—Administering brentuximab vedotin immediately after autologous stem cell transplant can improve progression-free survival (PFS) in patients with Hodgkin lymphoma (HL), results of the phase 3 AETHERA trial suggest.

The overall survival (OS) data for this study are not yet mature, but the significant improvement in PFS will likely translate to improved OS in a few years’ time, according to Craig Moskowitz, MD, of Memorial Sloan Kettering Cancer Center in New York.

Dr Moskowitz presented results from the AETHERA trial at the 2014 ASH Annual Meeting as abstract 673. The trial was funded by Seattle Genetics, Inc., and Takeda Pharmaceutical Company Limited, the companies developing brentuximab.

The trial included HL patients with at least one risk factor for progression. Eligible patients must have had a history of refractory HL, relapsed within a year of receiving frontline chemotherapy, and/or had disease outside of the lymph nodes at the time of pre-transplant relapse.

Researchers enrolled 329 patients, and they were randomized to receive brentuximab or placebo every 3 weeks for up to about a year. Baseline characteristics were similar between the 2 arms.

Dr Moskowitz pointed out that 43% of patients in the brentuximab arm and 48% in the placebo arm had required 2 or more prior salvage therapies, and 60% and 59%, respectively, had primary refractory HL.

Patients in both arms received a median of 15 treatment cycles, with an average of 12 cycles on the brentuximab arm and 11 cycles on the placebo arm.

“Patients who progressed in the placebo arm could be unblinded and subsequently receive brentuximab on a companion study,” Dr Moskowitz noted. “So technically, this was a cross-over design, making overall survival at 24 months quite unlikely.”

Efficacy/survival results

About half of patients in each arm completed treatment—47% in the brentuximab arm and 49% in the placebo arm. The reasons for discontinuation included disease progression (15% and 42%, respectively), adverse events (33% and 6%, respectively), and patient decision (5% and 2%, respectively).

Still, the trial achieved its primary endpoint, demonstrating a significant increase in PFS, according to an independent review facility (IRF).

The median PFS per the IRF was 43 months for patients in the brentuximab arm and 24 months in the placebo arm (hazard ratio=0.57, P=0.001). The 2-year PFS rates per the IRF were 63% and 51%, respectively.

The 2-year PFS rate according to investigators was 65% in the brentuximab arm and 45% in the placebo arm. The median PFS per investigators has not yet been reached for brentuximab but was 16 months for placebo.

The PFS benefit was consistent across all pre-specified subgroups, Dr Moskowitz noted, including primary refractory patients, patients who relapsed within 12 months of frontline therapy, and patients who relapsed after 12 months with extranodal disease.

Patients who experienced disease progression received a variety of subsequent therapies.

In the brentuximab arm, 16% of patients receiving subsequent therapy were treated with brentuximab after relapse. In the placebo arm, 85% of patients receiving subsequent therapy were treated with single-agent brentuximab.

Twenty-eight percent of patients in the placebo arm and 25% in the brentuximab arm received stem cell transplant as subsequent therapy, the majority of which were allogeneic transplants. Dr Moskowitz said a second transplant could have improved survival in these patients, but whether it actually did is unclear.

He noted that the OS data are immature, but there is currently no significant difference in OS between the treatment arms (hazard ratio=1.15; P=0.62).

“The median follow-up right now is 24 months,” he said. “So one will have to wait for a survival advantage or disadvantage, but from my point of view, a PFS of 65% at 2 years will translate to an overall survival difference. We’re just going to have to wait a few more years.”

Dr Moskowitz said another analysis of OS is planned in 2016.

Safety data

The most common adverse events in the brentuximab arm were peripheral sensory neuropathy (56%), neutropenia (35%), upper respiratory tract infection (26%), fatigue (24%), and peripheral motor neuropathy (23%).

The most common adverse events in the placebo arm were upper respiratory tract infection (23%), fatigue (18%), peripheral sensory neuropathy (16%), cough (16%), and neutropenia (12%).

Eighty-five percent of patients with peripheral neuropathy in the brentuximab arm had a resolution or improvement in symptoms, with a median time to improvement of 23.4 weeks.

Grade 3 or higher adverse events in the brentuximab arm included neutropenia, peripheral sensory neuropathy, peripheral motor neuropathy, nausea, fatigue, and diarrhea.

Grade 3 or higher adverse events in the placebo arm included neutropenia, fatigue, peripheral motor neuropathy, diarrhea, and peripheral sensory neuropathy. No Grade 4 peripheral neuropathy events occurred.

One death occurred within 30 days of brentuximab treatment. The patient died from treatment-related acute respiratory distress syndrome (ARDS) associated with pneumonitis.

Another death occurred on the brentuximab arm at day 40 from ARDS following an episode of treatment-related acute pancreatitis, which had resolved at the time of death.

Nevertheless, Dr Moskowitz characterized brentuximab consolidation as “very well-tolerated” in this patient population.

He concluded, “For patients with a remission duration of less than a year, patients with primary refractory Hodgkin lymphoma, and patients with Hodgkin lymphoma with extranodal involvement, I do believe this will become standard treatment.”

SAN FRANCISCO—Administering brentuximab vedotin immediately after autologous stem cell transplant can improve progression-free survival (PFS) in patients with Hodgkin lymphoma (HL), results of the phase 3 AETHERA trial suggest.

The overall survival (OS) data for this study are not yet mature, but the significant improvement in PFS will likely translate to improved OS in a few years’ time, according to Craig Moskowitz, MD, of Memorial Sloan Kettering Cancer Center in New York.

Dr Moskowitz presented results from the AETHERA trial at the 2014 ASH Annual Meeting as abstract 673. The trial was funded by Seattle Genetics, Inc., and Takeda Pharmaceutical Company Limited, the companies developing brentuximab.

The trial included HL patients with at least one risk factor for progression. Eligible patients must have had a history of refractory HL, relapsed within a year of receiving frontline chemotherapy, and/or had disease outside of the lymph nodes at the time of pre-transplant relapse.

Researchers enrolled 329 patients, and they were randomized to receive brentuximab or placebo every 3 weeks for up to about a year. Baseline characteristics were similar between the 2 arms.

Dr Moskowitz pointed out that 43% of patients in the brentuximab arm and 48% in the placebo arm had required 2 or more prior salvage therapies, and 60% and 59%, respectively, had primary refractory HL.

Patients in both arms received a median of 15 treatment cycles, with an average of 12 cycles on the brentuximab arm and 11 cycles on the placebo arm.

“Patients who progressed in the placebo arm could be unblinded and subsequently receive brentuximab on a companion study,” Dr Moskowitz noted. “So technically, this was a cross-over design, making overall survival at 24 months quite unlikely.”

Efficacy/survival results

About half of patients in each arm completed treatment—47% in the brentuximab arm and 49% in the placebo arm. The reasons for discontinuation included disease progression (15% and 42%, respectively), adverse events (33% and 6%, respectively), and patient decision (5% and 2%, respectively).

Still, the trial achieved its primary endpoint, demonstrating a significant increase in PFS, according to an independent review facility (IRF).

The median PFS per the IRF was 43 months for patients in the brentuximab arm and 24 months in the placebo arm (hazard ratio=0.57, P=0.001). The 2-year PFS rates per the IRF were 63% and 51%, respectively.

The 2-year PFS rate according to investigators was 65% in the brentuximab arm and 45% in the placebo arm. The median PFS per investigators has not yet been reached for brentuximab but was 16 months for placebo.

The PFS benefit was consistent across all pre-specified subgroups, Dr Moskowitz noted, including primary refractory patients, patients who relapsed within 12 months of frontline therapy, and patients who relapsed after 12 months with extranodal disease.

Patients who experienced disease progression received a variety of subsequent therapies.

In the brentuximab arm, 16% of patients receiving subsequent therapy were treated with brentuximab after relapse. In the placebo arm, 85% of patients receiving subsequent therapy were treated with single-agent brentuximab.

Twenty-eight percent of patients in the placebo arm and 25% in the brentuximab arm received stem cell transplant as subsequent therapy, the majority of which were allogeneic transplants. Dr Moskowitz said a second transplant could have improved survival in these patients, but whether it actually did is unclear.

He noted that the OS data are immature, but there is currently no significant difference in OS between the treatment arms (hazard ratio=1.15; P=0.62).

“The median follow-up right now is 24 months,” he said. “So one will have to wait for a survival advantage or disadvantage, but from my point of view, a PFS of 65% at 2 years will translate to an overall survival difference. We’re just going to have to wait a few more years.”

Dr Moskowitz said another analysis of OS is planned in 2016.

Safety data

The most common adverse events in the brentuximab arm were peripheral sensory neuropathy (56%), neutropenia (35%), upper respiratory tract infection (26%), fatigue (24%), and peripheral motor neuropathy (23%).

The most common adverse events in the placebo arm were upper respiratory tract infection (23%), fatigue (18%), peripheral sensory neuropathy (16%), cough (16%), and neutropenia (12%).

Eighty-five percent of patients with peripheral neuropathy in the brentuximab arm had a resolution or improvement in symptoms, with a median time to improvement of 23.4 weeks.

Grade 3 or higher adverse events in the brentuximab arm included neutropenia, peripheral sensory neuropathy, peripheral motor neuropathy, nausea, fatigue, and diarrhea.

Grade 3 or higher adverse events in the placebo arm included neutropenia, fatigue, peripheral motor neuropathy, diarrhea, and peripheral sensory neuropathy. No Grade 4 peripheral neuropathy events occurred.

One death occurred within 30 days of brentuximab treatment. The patient died from treatment-related acute respiratory distress syndrome (ARDS) associated with pneumonitis.

Another death occurred on the brentuximab arm at day 40 from ARDS following an episode of treatment-related acute pancreatitis, which had resolved at the time of death.

Nevertheless, Dr Moskowitz characterized brentuximab consolidation as “very well-tolerated” in this patient population.

He concluded, “For patients with a remission duration of less than a year, patients with primary refractory Hodgkin lymphoma, and patients with Hodgkin lymphoma with extranodal involvement, I do believe this will become standard treatment.”

Attendees at ASH 2014

SAN FRANCISCO—Multiple myeloma (MM) is driven to spread by only a subset of the myeloma cells within a patient’s body, according to research presented at the 2014 ASH Annual Meeting.

Attacking those cells with targeted drugs may degrade MM’s ability to spread throughout the bone marrow, study investigators said.

The team had used a mouse model of MM to track which of 15 subclones of myeloma cells spread beyond their initial site in the animals’ hind legs.

By labeling the different subgroups with fluorescent dyes, the researchers determined that just one of the subclones was responsible for disease metastasis.

They then compared the pattern of gene abnormalities in the initial myeloma tissue and the metastatic tumors. And they found that 238 genes were significantly less active in the latter group, comprising a gene signature of metastatic myeloma.

“Out of all the genes that were differently expressed in the 2 groups, we found 11 that played a functional role in metastasis and therefore may be drivers of the disease,” said study investigator Irene Ghobrial, MD, of the Dana-Farber Cancer Institute in Boston.

If future studies confirm that role, the genes may become targets for therapies that inhibit MM metastasis, she added.

Dr Ghobrial and her colleagues presented this research in a poster session at ASH (abstract 3370).

Attendees at ASH 2014

SAN FRANCISCO—Multiple myeloma (MM) is driven to spread by only a subset of the myeloma cells within a patient’s body, according to research presented at the 2014 ASH Annual Meeting.

Attacking those cells with targeted drugs may degrade MM’s ability to spread throughout the bone marrow, study investigators said.

The team had used a mouse model of MM to track which of 15 subclones of myeloma cells spread beyond their initial site in the animals’ hind legs.

By labeling the different subgroups with fluorescent dyes, the researchers determined that just one of the subclones was responsible for disease metastasis.

They then compared the pattern of gene abnormalities in the initial myeloma tissue and the metastatic tumors. And they found that 238 genes were significantly less active in the latter group, comprising a gene signature of metastatic myeloma.

“Out of all the genes that were differently expressed in the 2 groups, we found 11 that played a functional role in metastasis and therefore may be drivers of the disease,” said study investigator Irene Ghobrial, MD, of the Dana-Farber Cancer Institute in Boston.

If future studies confirm that role, the genes may become targets for therapies that inhibit MM metastasis, she added.

Dr Ghobrial and her colleagues presented this research in a poster session at ASH (abstract 3370).

Attendees at ASH 2014

SAN FRANCISCO—Multiple myeloma (MM) is driven to spread by only a subset of the myeloma cells within a patient’s body, according to research presented at the 2014 ASH Annual Meeting.

Attacking those cells with targeted drugs may degrade MM’s ability to spread throughout the bone marrow, study investigators said.

The team had used a mouse model of MM to track which of 15 subclones of myeloma cells spread beyond their initial site in the animals’ hind legs.

By labeling the different subgroups with fluorescent dyes, the researchers determined that just one of the subclones was responsible for disease metastasis.

They then compared the pattern of gene abnormalities in the initial myeloma tissue and the metastatic tumors. And they found that 238 genes were significantly less active in the latter group, comprising a gene signature of metastatic myeloma.

“Out of all the genes that were differently expressed in the 2 groups, we found 11 that played a functional role in metastasis and therefore may be drivers of the disease,” said study investigator Irene Ghobrial, MD, of the Dana-Farber Cancer Institute in Boston.

If future studies confirm that role, the genes may become targets for therapies that inhibit MM metastasis, she added.

Dr Ghobrial and her colleagues presented this research in a poster session at ASH (abstract 3370).

SAN FRANCISCO – Adding a kinase inhibitor to a standard regimen for acute myeloid leukemia can prolong event-free and relapse-free survival in young adult patients, but the effect on overall survival is still unclear, investigators reported.

In a randomized controlled trial, 3-year event-free survival (EFS), the primary endpoint, was 40% among patients treated with chemotherapy and sorafenib (Nexavar), compared with 22% for patients treated with chemotherapy and a placebo (P = .013). The median EFS was 21 months and 9 months, respectively, reported Dr. Christoph Röllig of University Hospital in Dresden, Germany.

Relapse-free survival (RFS) at 3 years was 56% in the sorafenib-treated group, compared with 38% in the placebo group (P = .017). The median RFS was not reached in the sorafenib group, vs. 23 months in the placebo group, Dr. Röllig reported at the annual meeting of the American Society of Hematology.

“These data constitute the first randomized evidence that actually kinase inhibitors work in AML. What we judge is that, according to evidence-based medicine principles, a comparatory trial would be desirable in order to establish sorafenib in AML treatment,” he said at a briefing prior to his presentation of the data in a plenary session.

Dr. Röllig and colleagues in 25 centers enrolled patients from 18 to 60 years with newly diagnosed AML. Of the 276 enrolled, 267 went on to receive study treatment: 134 were assigned to sorafenib and 133 to placebo. The study drug was given along a chemotherapy regimen consisting of two cycles of induction with daunorubicin and cytarabine followed by three cycles of high-dose cytarabine consolidation. Patients who did not have a response after the first cycle of daunorubicin induction underwent a second induction attempt with cytarabine and mitoxantrone.

The assigned study medication was given on days 10-19 of induction cycles one and two, from day 8 of each consolidation cycle until 3 days before the start of the next consolidation cycle, and as maintenance for 12 months after the end of consolidation.

As noted before, EFS in an intention-to-treat analysis censored for stem-cell therapy favored the sorafenib-treated patients, as did RFS. In addition, there was evidence to suggest a benefit trend toward prolonged RFS and overall survival with sorafenib among patients positive for the FLT3-ITD mutation, which has been shown to be sensitive to kinase inhibitors.

Patients in the sorafenib arm had significantly more episodes of fever, bleeding events, and the hand-foot syndrome, but there were no significant differences in other adverse events, Dr. Röllig said.

In an interview, he said that the investigators chose sorafenib because of its good track record and its efficacy against multiple kinases. His center is also involved in clinical trials exploring whether a different kinase inhibitor, quizartinib, has similar or better efficacy against AML.

The study was supported by Bayer. Dr. Röllig reported having no relevant disclosures.

SAN FRANCISCO – Adding a kinase inhibitor to a standard regimen for acute myeloid leukemia can prolong event-free and relapse-free survival in young adult patients, but the effect on overall survival is still unclear, investigators reported.

In a randomized controlled trial, 3-year event-free survival (EFS), the primary endpoint, was 40% among patients treated with chemotherapy and sorafenib (Nexavar), compared with 22% for patients treated with chemotherapy and a placebo (P = .013). The median EFS was 21 months and 9 months, respectively, reported Dr. Christoph Röllig of University Hospital in Dresden, Germany.

Relapse-free survival (RFS) at 3 years was 56% in the sorafenib-treated group, compared with 38% in the placebo group (P = .017). The median RFS was not reached in the sorafenib group, vs. 23 months in the placebo group, Dr. Röllig reported at the annual meeting of the American Society of Hematology.

“These data constitute the first randomized evidence that actually kinase inhibitors work in AML. What we judge is that, according to evidence-based medicine principles, a comparatory trial would be desirable in order to establish sorafenib in AML treatment,” he said at a briefing prior to his presentation of the data in a plenary session.

Dr. Röllig and colleagues in 25 centers enrolled patients from 18 to 60 years with newly diagnosed AML. Of the 276 enrolled, 267 went on to receive study treatment: 134 were assigned to sorafenib and 133 to placebo. The study drug was given along a chemotherapy regimen consisting of two cycles of induction with daunorubicin and cytarabine followed by three cycles of high-dose cytarabine consolidation. Patients who did not have a response after the first cycle of daunorubicin induction underwent a second induction attempt with cytarabine and mitoxantrone.

The assigned study medication was given on days 10-19 of induction cycles one and two, from day 8 of each consolidation cycle until 3 days before the start of the next consolidation cycle, and as maintenance for 12 months after the end of consolidation.

As noted before, EFS in an intention-to-treat analysis censored for stem-cell therapy favored the sorafenib-treated patients, as did RFS. In addition, there was evidence to suggest a benefit trend toward prolonged RFS and overall survival with sorafenib among patients positive for the FLT3-ITD mutation, which has been shown to be sensitive to kinase inhibitors.

Patients in the sorafenib arm had significantly more episodes of fever, bleeding events, and the hand-foot syndrome, but there were no significant differences in other adverse events, Dr. Röllig said.

In an interview, he said that the investigators chose sorafenib because of its good track record and its efficacy against multiple kinases. His center is also involved in clinical trials exploring whether a different kinase inhibitor, quizartinib, has similar or better efficacy against AML.

The study was supported by Bayer. Dr. Röllig reported having no relevant disclosures.

SAN FRANCISCO – Adding a kinase inhibitor to a standard regimen for acute myeloid leukemia can prolong event-free and relapse-free survival in young adult patients, but the effect on overall survival is still unclear, investigators reported.

In a randomized controlled trial, 3-year event-free survival (EFS), the primary endpoint, was 40% among patients treated with chemotherapy and sorafenib (Nexavar), compared with 22% for patients treated with chemotherapy and a placebo (P = .013). The median EFS was 21 months and 9 months, respectively, reported Dr. Christoph Röllig of University Hospital in Dresden, Germany.

Relapse-free survival (RFS) at 3 years was 56% in the sorafenib-treated group, compared with 38% in the placebo group (P = .017). The median RFS was not reached in the sorafenib group, vs. 23 months in the placebo group, Dr. Röllig reported at the annual meeting of the American Society of Hematology.

“These data constitute the first randomized evidence that actually kinase inhibitors work in AML. What we judge is that, according to evidence-based medicine principles, a comparatory trial would be desirable in order to establish sorafenib in AML treatment,” he said at a briefing prior to his presentation of the data in a plenary session.

Dr. Röllig and colleagues in 25 centers enrolled patients from 18 to 60 years with newly diagnosed AML. Of the 276 enrolled, 267 went on to receive study treatment: 134 were assigned to sorafenib and 133 to placebo. The study drug was given along a chemotherapy regimen consisting of two cycles of induction with daunorubicin and cytarabine followed by three cycles of high-dose cytarabine consolidation. Patients who did not have a response after the first cycle of daunorubicin induction underwent a second induction attempt with cytarabine and mitoxantrone.

The assigned study medication was given on days 10-19 of induction cycles one and two, from day 8 of each consolidation cycle until 3 days before the start of the next consolidation cycle, and as maintenance for 12 months after the end of consolidation.

As noted before, EFS in an intention-to-treat analysis censored for stem-cell therapy favored the sorafenib-treated patients, as did RFS. In addition, there was evidence to suggest a benefit trend toward prolonged RFS and overall survival with sorafenib among patients positive for the FLT3-ITD mutation, which has been shown to be sensitive to kinase inhibitors.

Patients in the sorafenib arm had significantly more episodes of fever, bleeding events, and the hand-foot syndrome, but there were no significant differences in other adverse events, Dr. Röllig said.

In an interview, he said that the investigators chose sorafenib because of its good track record and its efficacy against multiple kinases. His center is also involved in clinical trials exploring whether a different kinase inhibitor, quizartinib, has similar or better efficacy against AML.

The study was supported by Bayer. Dr. Röllig reported having no relevant disclosures.