EHA Congress 2015

Farhad Ravandi, MD

Photo courtesy of ASH

VIENNA—Adding the anticancer quinolone derivative vosaroxin to treatment with cytarabine can improve outcomes for some older patients with relapsed/refractory acute myeloid leukemia (AML), results of the phase 3 VALOR trial suggest.

AML patients age 60 and older with refractory and early relapse disease had improved survival rates when they received vosaroxin and cytarabine, compared to patients who received cytarabine and placebo.

However, for older patients with late-relapse AML, the addition of vosaroxin had no significant impact on survival.

Farhad Ravandi, MD, of the University of Texas MD Anderson Cancer Center in Houston, and his colleagues presented these result at the 20th Congress of the European Hematology Association (abstract P197*). The trial was sponsored by Sunesis Pharmaceuticals, the company developing vosaroxin.

“AML is a disease that primarily affects older patients, and clinical outcomes among these patients is abysmal,” Dr Ravandi noted. “These patients have had few options outside of clinical trial enrollment.”

“Results from the analyses presented today show compelling survival and durable responses, with comparable early mortality, for the vosaroxin and cytarabine treatment arm in the older refractory and early relapse patients. Given these results, I believe vosaroxin represents an important new treatment option.”

VALOR is a randomized, double-blind, phase 3 trial that enrolled 711 adult patients with relapsed or refractory AML. Patients were stratified for age, geographic region, and disease status, then randomized 1:1 to receive vosaroxin and cytarabine or placebo and cytarabine.

Dr Ravandi and his colleagues presented results from the subgroups of patients age 60 years and older (451/711) with late-relapse disease (n=87) and refractory or early relapse disease (combined n=364).

Late-relapse disease

Patients with late-relapse disease had a significantly higher complete response (CR) rate if they received vosaroxin/cytarabine rather than placebo/cytarabine. The rates were 57% and 28%, respectively (P=0.0064).

However, there was no significant difference between the treatment arms with regard to overall survival (OS), leukemia-free survival (LFS), or event-free survival (EFS).

The median OS was 9.2 months in the vosaroxin/cytarabine arm and 9.8 months in the placebo/cytarabine arm (hazard ratio [HR]=1.06, P=0.82). The median OS, censored for transplant, was 9.1 months in both arms (HR=0.92, P=0.78).

The median LFS was 10.3 months in the vosaroxin/cytarabine arm and 8.7 months in the placebo/cytarabine arm (HR=1.16, P=0.77). And the median EFS was 5.5 months and 2.3 months, respectively (HR=0.65, P=0.0852).

Thirty-day all-cause mortality was 11% the vosaroxin/cytarabine arm and 2% in the placebo/cytarabine arm. Sixty-day all-cause mortality was 18% and 14%, respectively.

Refractory/early relapse disease

Patients with refractory AML (n=210) and those with early relapse disease (n=154) had significant improvements in CR and survival when they received vosaroxin and cytarabine. The CR rate was 26% in the vosaroxin/cytarabine arm and 10% in the placebo/cytarabine arm (P=0.0001).

The median OS was 6.5 months in the vosaroxin/cytarabine arm and 3.9 months in the placebo/cytarabine arm (HR=0.69, P=0.0008). The median OS, censored for transplant, was 6.2 months and 3.9 months, respectively (HR=0.71, P=0.0048).

The median LFS was 9.7 months in the vosaroxin/cytarabine arm and 5.5 months in the placebo/cytarabine arm (HR=0.50, P=0.0424). And the median EFS was 1.7 months and 1.3 months, respectively (HR=0.59, P<0.0001).

Rates of all-cause mortality were comparable between the arms. Thirty-day all-cause mortality was 10% in the vosaroxin/cytarabine arm and 11% in the placebo/cytarabine arm. Sixty-day all-cause mortality was 21% and 25%, respectively.

Adverse events

Ninety-four percent of patients in the vosaroxin/cytarabine arm and 86% of those in the placebo/cytarabine arm experienced a grade 3 or higher adverse event (AE). The rate of treatment-related, grade 3 or higher AEs was 74% and 60%, respectively.

The most common grade 3 or higher AEs—occurring in at least 10% of patients in the vosaroxin/cytarabine and placebo/cytarabine arms, respectively—were febrile neutropenia (43% vs 30%), thrombocytopenia (24% vs 25%), anemia (23% vs 24%), neutropenia (19% vs 14%), hypokalemia (15% vs 7%), stomatitis (16% vs 4%), sepsis (12% vs 6%), and pneumonia (11% vs 8%).

*Information in the abstract differs from that presented at the meeting.

Farhad Ravandi, MD

Photo courtesy of ASH

VIENNA—Adding the anticancer quinolone derivative vosaroxin to treatment with cytarabine can improve outcomes for some older patients with relapsed/refractory acute myeloid leukemia (AML), results of the phase 3 VALOR trial suggest.

AML patients age 60 and older with refractory and early relapse disease had improved survival rates when they received vosaroxin and cytarabine, compared to patients who received cytarabine and placebo.

However, for older patients with late-relapse AML, the addition of vosaroxin had no significant impact on survival.

Farhad Ravandi, MD, of the University of Texas MD Anderson Cancer Center in Houston, and his colleagues presented these result at the 20th Congress of the European Hematology Association (abstract P197*). The trial was sponsored by Sunesis Pharmaceuticals, the company developing vosaroxin.

“AML is a disease that primarily affects older patients, and clinical outcomes among these patients is abysmal,” Dr Ravandi noted. “These patients have had few options outside of clinical trial enrollment.”

“Results from the analyses presented today show compelling survival and durable responses, with comparable early mortality, for the vosaroxin and cytarabine treatment arm in the older refractory and early relapse patients. Given these results, I believe vosaroxin represents an important new treatment option.”

VALOR is a randomized, double-blind, phase 3 trial that enrolled 711 adult patients with relapsed or refractory AML. Patients were stratified for age, geographic region, and disease status, then randomized 1:1 to receive vosaroxin and cytarabine or placebo and cytarabine.

Dr Ravandi and his colleagues presented results from the subgroups of patients age 60 years and older (451/711) with late-relapse disease (n=87) and refractory or early relapse disease (combined n=364).

Late-relapse disease

Patients with late-relapse disease had a significantly higher complete response (CR) rate if they received vosaroxin/cytarabine rather than placebo/cytarabine. The rates were 57% and 28%, respectively (P=0.0064).

However, there was no significant difference between the treatment arms with regard to overall survival (OS), leukemia-free survival (LFS), or event-free survival (EFS).

The median OS was 9.2 months in the vosaroxin/cytarabine arm and 9.8 months in the placebo/cytarabine arm (hazard ratio [HR]=1.06, P=0.82). The median OS, censored for transplant, was 9.1 months in both arms (HR=0.92, P=0.78).

The median LFS was 10.3 months in the vosaroxin/cytarabine arm and 8.7 months in the placebo/cytarabine arm (HR=1.16, P=0.77). And the median EFS was 5.5 months and 2.3 months, respectively (HR=0.65, P=0.0852).

Thirty-day all-cause mortality was 11% the vosaroxin/cytarabine arm and 2% in the placebo/cytarabine arm. Sixty-day all-cause mortality was 18% and 14%, respectively.

Refractory/early relapse disease

Patients with refractory AML (n=210) and those with early relapse disease (n=154) had significant improvements in CR and survival when they received vosaroxin and cytarabine. The CR rate was 26% in the vosaroxin/cytarabine arm and 10% in the placebo/cytarabine arm (P=0.0001).

The median OS was 6.5 months in the vosaroxin/cytarabine arm and 3.9 months in the placebo/cytarabine arm (HR=0.69, P=0.0008). The median OS, censored for transplant, was 6.2 months and 3.9 months, respectively (HR=0.71, P=0.0048).

The median LFS was 9.7 months in the vosaroxin/cytarabine arm and 5.5 months in the placebo/cytarabine arm (HR=0.50, P=0.0424). And the median EFS was 1.7 months and 1.3 months, respectively (HR=0.59, P<0.0001).

Rates of all-cause mortality were comparable between the arms. Thirty-day all-cause mortality was 10% in the vosaroxin/cytarabine arm and 11% in the placebo/cytarabine arm. Sixty-day all-cause mortality was 21% and 25%, respectively.

Adverse events

Ninety-four percent of patients in the vosaroxin/cytarabine arm and 86% of those in the placebo/cytarabine arm experienced a grade 3 or higher adverse event (AE). The rate of treatment-related, grade 3 or higher AEs was 74% and 60%, respectively.

The most common grade 3 or higher AEs—occurring in at least 10% of patients in the vosaroxin/cytarabine and placebo/cytarabine arms, respectively—were febrile neutropenia (43% vs 30%), thrombocytopenia (24% vs 25%), anemia (23% vs 24%), neutropenia (19% vs 14%), hypokalemia (15% vs 7%), stomatitis (16% vs 4%), sepsis (12% vs 6%), and pneumonia (11% vs 8%).

*Information in the abstract differs from that presented at the meeting.

Farhad Ravandi, MD

Photo courtesy of ASH

VIENNA—Adding the anticancer quinolone derivative vosaroxin to treatment with cytarabine can improve outcomes for some older patients with relapsed/refractory acute myeloid leukemia (AML), results of the phase 3 VALOR trial suggest.

AML patients age 60 and older with refractory and early relapse disease had improved survival rates when they received vosaroxin and cytarabine, compared to patients who received cytarabine and placebo.

However, for older patients with late-relapse AML, the addition of vosaroxin had no significant impact on survival.

Farhad Ravandi, MD, of the University of Texas MD Anderson Cancer Center in Houston, and his colleagues presented these result at the 20th Congress of the European Hematology Association (abstract P197*). The trial was sponsored by Sunesis Pharmaceuticals, the company developing vosaroxin.

“AML is a disease that primarily affects older patients, and clinical outcomes among these patients is abysmal,” Dr Ravandi noted. “These patients have had few options outside of clinical trial enrollment.”

“Results from the analyses presented today show compelling survival and durable responses, with comparable early mortality, for the vosaroxin and cytarabine treatment arm in the older refractory and early relapse patients. Given these results, I believe vosaroxin represents an important new treatment option.”

VALOR is a randomized, double-blind, phase 3 trial that enrolled 711 adult patients with relapsed or refractory AML. Patients were stratified for age, geographic region, and disease status, then randomized 1:1 to receive vosaroxin and cytarabine or placebo and cytarabine.

Dr Ravandi and his colleagues presented results from the subgroups of patients age 60 years and older (451/711) with late-relapse disease (n=87) and refractory or early relapse disease (combined n=364).

Late-relapse disease

Patients with late-relapse disease had a significantly higher complete response (CR) rate if they received vosaroxin/cytarabine rather than placebo/cytarabine. The rates were 57% and 28%, respectively (P=0.0064).

However, there was no significant difference between the treatment arms with regard to overall survival (OS), leukemia-free survival (LFS), or event-free survival (EFS).

The median OS was 9.2 months in the vosaroxin/cytarabine arm and 9.8 months in the placebo/cytarabine arm (hazard ratio [HR]=1.06, P=0.82). The median OS, censored for transplant, was 9.1 months in both arms (HR=0.92, P=0.78).

The median LFS was 10.3 months in the vosaroxin/cytarabine arm and 8.7 months in the placebo/cytarabine arm (HR=1.16, P=0.77). And the median EFS was 5.5 months and 2.3 months, respectively (HR=0.65, P=0.0852).

Thirty-day all-cause mortality was 11% the vosaroxin/cytarabine arm and 2% in the placebo/cytarabine arm. Sixty-day all-cause mortality was 18% and 14%, respectively.

Refractory/early relapse disease

Patients with refractory AML (n=210) and those with early relapse disease (n=154) had significant improvements in CR and survival when they received vosaroxin and cytarabine. The CR rate was 26% in the vosaroxin/cytarabine arm and 10% in the placebo/cytarabine arm (P=0.0001).

The median OS was 6.5 months in the vosaroxin/cytarabine arm and 3.9 months in the placebo/cytarabine arm (HR=0.69, P=0.0008). The median OS, censored for transplant, was 6.2 months and 3.9 months, respectively (HR=0.71, P=0.0048).

The median LFS was 9.7 months in the vosaroxin/cytarabine arm and 5.5 months in the placebo/cytarabine arm (HR=0.50, P=0.0424). And the median EFS was 1.7 months and 1.3 months, respectively (HR=0.59, P<0.0001).

Rates of all-cause mortality were comparable between the arms. Thirty-day all-cause mortality was 10% in the vosaroxin/cytarabine arm and 11% in the placebo/cytarabine arm. Sixty-day all-cause mortality was 21% and 25%, respectively.

Adverse events

Ninety-four percent of patients in the vosaroxin/cytarabine arm and 86% of those in the placebo/cytarabine arm experienced a grade 3 or higher adverse event (AE). The rate of treatment-related, grade 3 or higher AEs was 74% and 60%, respectively.

The most common grade 3 or higher AEs—occurring in at least 10% of patients in the vosaroxin/cytarabine and placebo/cytarabine arms, respectively—were febrile neutropenia (43% vs 30%), thrombocytopenia (24% vs 25%), anemia (23% vs 24%), neutropenia (19% vs 14%), hypokalemia (15% vs 7%), stomatitis (16% vs 4%), sepsis (12% vs 6%), and pneumonia (11% vs 8%).

*Information in the abstract differs from that presented at the meeting.

VIENNA – Patients with chronic-phase chronic myeloid leukemia treated with first-line dasatinib achieved significantly more molecular responses at 2 years than those treated with imatinib in the SPIRIT 2 trial.

So far there is no difference, however, in disease progression or overall survival in the ongoing phase III trial, Dr. Stephen O’Brien reported at the annual congress of the European Hematology Association.

With 814 patients, SPIRIT 2 is the largest randomized trial of dasatinib (Sprycel) vs. imatinib (Gleevec).

Patrice Wendling/Frontline Medical News

Its design is similar to the ongoing 519-patient DASISION trial, which reported higher response rates with dasatinib than imatinib in the same setting, but similar progression-free and overall survival rates at 3-year follow-up.

The primary endpoint of SPIRIT 2 is event-free survival at 5 years and will be available in March 2018, he said. Patients at 172 hospitals in the United Kingdom were evenly randomized to imatinib 400 mg daily or dasatinib 100 mg daily. One patient in each group was excluded due to protocol violation or withdrawal of consent. Median follow-up is 42.4 months.

At 24 months, 60.6% of imatinib patients (246/406) and 71.4% of dasatinib patients (290/406) remained on treatment.

Significantly more patients treated with dasatinib than imatinib achieved a complete cytogenetic response at 12 months (53.3% vs. 42%; P = .003), but the difference was diminished at 24 months (33.7% vs. 27.5%; P = .189). These results should be interpreted with caution, however, because the data were incomplete, Dr. O’Brien, of Newcastle University Medical School, Newcastle upon Tyne, England, said.

He noted that the molecular data are more reliable and were calculated based on samples drawn within a 6-week window on either side of the 24-month time point. Values had to be imputed for 22 patients who had no 24-month sample taken, although this imputation should not impact survival outcomes, he said. Major molecular response was defined as a 3-log reduction in the BCR-ABL/ABL ratio, relative to baseline, with data also captured for patients achieving a 4-log reduction.

Significantly more patients on dasatinib than imatinib achieved an MR3 response (57.5% vs. 46%; P < .001) and MR^4.5 response (20.2% vs. 14.3%; P = .026).

More patients stopped imatinib than dasatinib due to investigator and/or patient concerns about inadequate response (10.8% vs. 1.3%), whereas nonhematologic toxicities drove more patients to abandon dasatinib (22% vs. 12%), according to Dr. O’Brien.

Pleural effusion, a known toxicity with dasatinib, occurred in 24.1% of patients given the drug vs. 1.2% given imatinib, requiring drainage in 22 cases vs. 1 case, respectively. There was also a “difficult-to-explain” signal for breathlessness with no obvious cause (15.5% vs. 8%). Hypertension was confirmed in only one of these cases and symptoms resolved in others when the drug was withdrawn, he said.

Serious cardiac adverse events were reported in 2.2% of patients in the imatinib arm and 4.2% in the dasatinib arm. Again, the results should be interpreted with caution because trials set up at the time of SPIRIT2 in 2008 were not designed to look carefully at this outcome, Dr. O’Brien observed.

In all, 38 patients have died; 19 in each group.

pwendling@frontlinemedcom.com

On Twitter@pwendl

*Correction 6/18/2015: The headline for an earlier version of this article misstated the type of cancer treated in this study.

VIENNA – Patients with chronic-phase chronic myeloid leukemia treated with first-line dasatinib achieved significantly more molecular responses at 2 years than those treated with imatinib in the SPIRIT 2 trial.

So far there is no difference, however, in disease progression or overall survival in the ongoing phase III trial, Dr. Stephen O’Brien reported at the annual congress of the European Hematology Association.

With 814 patients, SPIRIT 2 is the largest randomized trial of dasatinib (Sprycel) vs. imatinib (Gleevec).

Patrice Wendling/Frontline Medical News

Its design is similar to the ongoing 519-patient DASISION trial, which reported higher response rates with dasatinib than imatinib in the same setting, but similar progression-free and overall survival rates at 3-year follow-up.

The primary endpoint of SPIRIT 2 is event-free survival at 5 years and will be available in March 2018, he said. Patients at 172 hospitals in the United Kingdom were evenly randomized to imatinib 400 mg daily or dasatinib 100 mg daily. One patient in each group was excluded due to protocol violation or withdrawal of consent. Median follow-up is 42.4 months.

At 24 months, 60.6% of imatinib patients (246/406) and 71.4% of dasatinib patients (290/406) remained on treatment.

Significantly more patients treated with dasatinib than imatinib achieved a complete cytogenetic response at 12 months (53.3% vs. 42%; P = .003), but the difference was diminished at 24 months (33.7% vs. 27.5%; P = .189). These results should be interpreted with caution, however, because the data were incomplete, Dr. O’Brien, of Newcastle University Medical School, Newcastle upon Tyne, England, said.

He noted that the molecular data are more reliable and were calculated based on samples drawn within a 6-week window on either side of the 24-month time point. Values had to be imputed for 22 patients who had no 24-month sample taken, although this imputation should not impact survival outcomes, he said. Major molecular response was defined as a 3-log reduction in the BCR-ABL/ABL ratio, relative to baseline, with data also captured for patients achieving a 4-log reduction.

Significantly more patients on dasatinib than imatinib achieved an MR3 response (57.5% vs. 46%; P < .001) and MR^4.5 response (20.2% vs. 14.3%; P = .026).

More patients stopped imatinib than dasatinib due to investigator and/or patient concerns about inadequate response (10.8% vs. 1.3%), whereas nonhematologic toxicities drove more patients to abandon dasatinib (22% vs. 12%), according to Dr. O’Brien.

Pleural effusion, a known toxicity with dasatinib, occurred in 24.1% of patients given the drug vs. 1.2% given imatinib, requiring drainage in 22 cases vs. 1 case, respectively. There was also a “difficult-to-explain” signal for breathlessness with no obvious cause (15.5% vs. 8%). Hypertension was confirmed in only one of these cases and symptoms resolved in others when the drug was withdrawn, he said.

Serious cardiac adverse events were reported in 2.2% of patients in the imatinib arm and 4.2% in the dasatinib arm. Again, the results should be interpreted with caution because trials set up at the time of SPIRIT2 in 2008 were not designed to look carefully at this outcome, Dr. O’Brien observed.

In all, 38 patients have died; 19 in each group.

pwendling@frontlinemedcom.com

On Twitter@pwendl

*Correction 6/18/2015: The headline for an earlier version of this article misstated the type of cancer treated in this study.

VIENNA – Patients with chronic-phase chronic myeloid leukemia treated with first-line dasatinib achieved significantly more molecular responses at 2 years than those treated with imatinib in the SPIRIT 2 trial.

So far there is no difference, however, in disease progression or overall survival in the ongoing phase III trial, Dr. Stephen O’Brien reported at the annual congress of the European Hematology Association.

With 814 patients, SPIRIT 2 is the largest randomized trial of dasatinib (Sprycel) vs. imatinib (Gleevec).

Patrice Wendling/Frontline Medical News

Its design is similar to the ongoing 519-patient DASISION trial, which reported higher response rates with dasatinib than imatinib in the same setting, but similar progression-free and overall survival rates at 3-year follow-up.

The primary endpoint of SPIRIT 2 is event-free survival at 5 years and will be available in March 2018, he said. Patients at 172 hospitals in the United Kingdom were evenly randomized to imatinib 400 mg daily or dasatinib 100 mg daily. One patient in each group was excluded due to protocol violation or withdrawal of consent. Median follow-up is 42.4 months.

At 24 months, 60.6% of imatinib patients (246/406) and 71.4% of dasatinib patients (290/406) remained on treatment.

Significantly more patients treated with dasatinib than imatinib achieved a complete cytogenetic response at 12 months (53.3% vs. 42%; P = .003), but the difference was diminished at 24 months (33.7% vs. 27.5%; P = .189). These results should be interpreted with caution, however, because the data were incomplete, Dr. O’Brien, of Newcastle University Medical School, Newcastle upon Tyne, England, said.

He noted that the molecular data are more reliable and were calculated based on samples drawn within a 6-week window on either side of the 24-month time point. Values had to be imputed for 22 patients who had no 24-month sample taken, although this imputation should not impact survival outcomes, he said. Major molecular response was defined as a 3-log reduction in the BCR-ABL/ABL ratio, relative to baseline, with data also captured for patients achieving a 4-log reduction.

Significantly more patients on dasatinib than imatinib achieved an MR3 response (57.5% vs. 46%; P < .001) and MR^4.5 response (20.2% vs. 14.3%; P = .026).

More patients stopped imatinib than dasatinib due to investigator and/or patient concerns about inadequate response (10.8% vs. 1.3%), whereas nonhematologic toxicities drove more patients to abandon dasatinib (22% vs. 12%), according to Dr. O’Brien.

Pleural effusion, a known toxicity with dasatinib, occurred in 24.1% of patients given the drug vs. 1.2% given imatinib, requiring drainage in 22 cases vs. 1 case, respectively. There was also a “difficult-to-explain” signal for breathlessness with no obvious cause (15.5% vs. 8%). Hypertension was confirmed in only one of these cases and symptoms resolved in others when the drug was withdrawn, he said.

Serious cardiac adverse events were reported in 2.2% of patients in the imatinib arm and 4.2% in the dasatinib arm. Again, the results should be interpreted with caution because trials set up at the time of SPIRIT2 in 2008 were not designed to look carefully at this outcome, Dr. O’Brien observed.

In all, 38 patients have died; 19 in each group.

pwendling@frontlinemedcom.com

On Twitter@pwendl

*Correction 6/18/2015: The headline for an earlier version of this article misstated the type of cancer treated in this study.

VIENNA – A daily dose of the investigational BCL-2 inhibitor venetoclax plus rituximab induced responses in 84% of patients with relapsed or refractory chronic lymphocytic leukemia in a phase Ib study.

Of the 49 patients, 20 (41%) achieved a complete response by standard assessment and 13 (27%) achieved a complete response with no evidence of residual disease on flow cytometry.

Moreover, six patients elected to stop venetoclax after achieving a complete response and, to date, only one has had recurrence of disease after 24 months without therapy, lead investigator Dr. Andrew W. Roberts reported at the annual congress of the European Hematology Association.

Patrice Wendling/Frontline Medical News

Not only were patients able to come off treatment and continue to remain in complete response, but responses were seen at the same frequencies across all classes of cytogenetic and molecular abnormalities, he noted.

“The greatest advance that this drug brings is for those patients who currently have a terrible prognosis with all other drugs that we now have,” Dr. Roberts of Royal Melbourne Hospital said in a press briefing.

“This is an important step forward in finding chemotherapy-free regimens in these vulnerable, elderly patients,” said press briefing moderator Dr. Anton Hagenbeek of the University Medical Center, Utrecht, the Netherlands.

Patients in the open-label, dose-escalation study had received a median of two prior lines of therapy (range, one to five) for chronic lymphocytic leukemia (CLL); their median age was 68 years (50-88 years). They began treatment with 20 mg or 50 mg venetoclax daily, increasing weekly to final cohort doses of 200 mg to 600 mg. Six cycles of monthly standard rituximab were added after the weekly lead-in phase.

CLL depends on high levels of B-cell lymphoma-2 (BCL-2) to stay alive. Venetoclax binds to and switches off the BCL-2 protein function, triggering the death of the CLL cell.

Grade 3 or 4 adverse events occurring in more than 10% of patients were neutropenia (51%), thrombocytopenia (16%), and anemia (14%). There was one treatment-emergent case of tumor lysis syndrome leading to death early in the trial. This phenomenon can occur when the CLL breaks down very quickly and, as a consequence, the study was redesigned and a lower starting dose is now used, Dr. Roberts said.

“That problem has been eliminated, but we still see a very large improvement in patients in a few weeks,” he said. “Other than that, there is a little bit of neutropenia, but that is very manageable.”

“So do you think you are curing patients with this approach?” Dr. Hagenbeek asked, to which Dr. Roberts replied, “Too early to say.”

Venetoclax is currently being evaluated in less heavily pretreated patients and a phase III trial is comparing the combination of venetoclax and rituximab with standard bendamustine chemotherapy plus rituximab, he said.

In May, the Food and Drug Administration granted venetoclax breakthrough therapy designation for use in relapsed or refractory chronic lymphocytic leukemia with a 17p deletion mutation.

AbbVie, which is developing venetoclax in partnership with Roche and Genentech, plans to submit regulatory applications for venetoclax to the FDA and the European Medicines Agency before the end of 2015.

pwendling@frontlinemedcom.com

On Twitter @pwendl

VIENNA – A daily dose of the investigational BCL-2 inhibitor venetoclax plus rituximab induced responses in 84% of patients with relapsed or refractory chronic lymphocytic leukemia in a phase Ib study.

Of the 49 patients, 20 (41%) achieved a complete response by standard assessment and 13 (27%) achieved a complete response with no evidence of residual disease on flow cytometry.

Moreover, six patients elected to stop venetoclax after achieving a complete response and, to date, only one has had recurrence of disease after 24 months without therapy, lead investigator Dr. Andrew W. Roberts reported at the annual congress of the European Hematology Association.

Patrice Wendling/Frontline Medical News

Not only were patients able to come off treatment and continue to remain in complete response, but responses were seen at the same frequencies across all classes of cytogenetic and molecular abnormalities, he noted.

“The greatest advance that this drug brings is for those patients who currently have a terrible prognosis with all other drugs that we now have,” Dr. Roberts of Royal Melbourne Hospital said in a press briefing.

“This is an important step forward in finding chemotherapy-free regimens in these vulnerable, elderly patients,” said press briefing moderator Dr. Anton Hagenbeek of the University Medical Center, Utrecht, the Netherlands.

Patients in the open-label, dose-escalation study had received a median of two prior lines of therapy (range, one to five) for chronic lymphocytic leukemia (CLL); their median age was 68 years (50-88 years). They began treatment with 20 mg or 50 mg venetoclax daily, increasing weekly to final cohort doses of 200 mg to 600 mg. Six cycles of monthly standard rituximab were added after the weekly lead-in phase.

CLL depends on high levels of B-cell lymphoma-2 (BCL-2) to stay alive. Venetoclax binds to and switches off the BCL-2 protein function, triggering the death of the CLL cell.

Grade 3 or 4 adverse events occurring in more than 10% of patients were neutropenia (51%), thrombocytopenia (16%), and anemia (14%). There was one treatment-emergent case of tumor lysis syndrome leading to death early in the trial. This phenomenon can occur when the CLL breaks down very quickly and, as a consequence, the study was redesigned and a lower starting dose is now used, Dr. Roberts said.

“That problem has been eliminated, but we still see a very large improvement in patients in a few weeks,” he said. “Other than that, there is a little bit of neutropenia, but that is very manageable.”

“So do you think you are curing patients with this approach?” Dr. Hagenbeek asked, to which Dr. Roberts replied, “Too early to say.”

Venetoclax is currently being evaluated in less heavily pretreated patients and a phase III trial is comparing the combination of venetoclax and rituximab with standard bendamustine chemotherapy plus rituximab, he said.

In May, the Food and Drug Administration granted venetoclax breakthrough therapy designation for use in relapsed or refractory chronic lymphocytic leukemia with a 17p deletion mutation.

AbbVie, which is developing venetoclax in partnership with Roche and Genentech, plans to submit regulatory applications for venetoclax to the FDA and the European Medicines Agency before the end of 2015.

pwendling@frontlinemedcom.com

On Twitter @pwendl

VIENNA – A daily dose of the investigational BCL-2 inhibitor venetoclax plus rituximab induced responses in 84% of patients with relapsed or refractory chronic lymphocytic leukemia in a phase Ib study.

Of the 49 patients, 20 (41%) achieved a complete response by standard assessment and 13 (27%) achieved a complete response with no evidence of residual disease on flow cytometry.

Moreover, six patients elected to stop venetoclax after achieving a complete response and, to date, only one has had recurrence of disease after 24 months without therapy, lead investigator Dr. Andrew W. Roberts reported at the annual congress of the European Hematology Association.

Patrice Wendling/Frontline Medical News

Not only were patients able to come off treatment and continue to remain in complete response, but responses were seen at the same frequencies across all classes of cytogenetic and molecular abnormalities, he noted.

“The greatest advance that this drug brings is for those patients who currently have a terrible prognosis with all other drugs that we now have,” Dr. Roberts of Royal Melbourne Hospital said in a press briefing.

“This is an important step forward in finding chemotherapy-free regimens in these vulnerable, elderly patients,” said press briefing moderator Dr. Anton Hagenbeek of the University Medical Center, Utrecht, the Netherlands.

Patients in the open-label, dose-escalation study had received a median of two prior lines of therapy (range, one to five) for chronic lymphocytic leukemia (CLL); their median age was 68 years (50-88 years). They began treatment with 20 mg or 50 mg venetoclax daily, increasing weekly to final cohort doses of 200 mg to 600 mg. Six cycles of monthly standard rituximab were added after the weekly lead-in phase.

CLL depends on high levels of B-cell lymphoma-2 (BCL-2) to stay alive. Venetoclax binds to and switches off the BCL-2 protein function, triggering the death of the CLL cell.

Grade 3 or 4 adverse events occurring in more than 10% of patients were neutropenia (51%), thrombocytopenia (16%), and anemia (14%). There was one treatment-emergent case of tumor lysis syndrome leading to death early in the trial. This phenomenon can occur when the CLL breaks down very quickly and, as a consequence, the study was redesigned and a lower starting dose is now used, Dr. Roberts said.

“That problem has been eliminated, but we still see a very large improvement in patients in a few weeks,” he said. “Other than that, there is a little bit of neutropenia, but that is very manageable.”

“So do you think you are curing patients with this approach?” Dr. Hagenbeek asked, to which Dr. Roberts replied, “Too early to say.”

Venetoclax is currently being evaluated in less heavily pretreated patients and a phase III trial is comparing the combination of venetoclax and rituximab with standard bendamustine chemotherapy plus rituximab, he said.

In May, the Food and Drug Administration granted venetoclax breakthrough therapy designation for use in relapsed or refractory chronic lymphocytic leukemia with a 17p deletion mutation.

AbbVie, which is developing venetoclax in partnership with Roche and Genentech, plans to submit regulatory applications for venetoclax to the FDA and the European Medicines Agency before the end of 2015.

pwendling@frontlinemedcom.com

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