Efficacy and safety of VENCLEXTA in acute myeloid leukemia (AML) were evaluated in combination with azacitidine (AZA), decitabine (DEC), or low-dose cytarabine (LDAC) 1

STUDY M14-358: OPEN-LABEL, NON-RANDOMIZED, PHASE 1B STUDY OF VENCLEXTA IN COMBINATION WITH AZA OR DEC 1

Diagram showing M14-358 study results: 80 patients with newly diagnosed AML ineligible for intensive chemotherapy participated in an open-label, non-randomized study of VENCLEXTA in combination with azacitidine or decitabine. Patients were age 75 or older or had at least one of the following criteria: baseline ECOG performance status or 2-3, moderate hepatic impairment, severe cardiac or pulmonary comorbidity or CLcr <45 mL/min or other comorbidity. 84 patients received VENCLEXTA with a daily ramp-up starting from 100 mg to 200 mg, and then to a final dose of 400 mg/day and azacitidine 75/mg/m2 IV or SC days 1-2 of each 28-day cycle beginning cycle 1, day 1. 31 patients received VENCLEXTA with a daily ramp-up starting from 100 mg to 200 mg and then to a final dose of 400/mg per day or decitabine 20 mg/m2 IV days 1-5 of each 28-day cycle beginning cycle 1, day 1. Treatment for both the 84 patient group and 31 patient group was continued until disease progression or unacceptable toxicity. Endpoints included: complete remission, complete remission with partial hematological recovery, time to first complete remission or complete remission with partial hematological recovery, median observed time in remission for those who achieved complete remission, or stem cell transplantation.

STUDY M14-387: OPEN-LABEL, NON-RANDOMIZED, PHASE 1/2 STUDY OF VENCLEXTA IN COMBINATION WITH LDAC 1

Diagram showing M14-387 study results: 61 patients with newly diagnosed AML ineligible for intensive chemotherapy participated. Patients were age 75 or older or had at least one of the following criteria: baseline ECOG performance status of 2-3, severe cardiac or pulmonary comorbidity, moderate hepatic impairment or CLcr <45 mL/min or other comorbidity. All patients received VENCLEXTA with a daily ramp-up starting from 100 mg to 200 mg to 400 mg and then to a final dose of 600 mg per day in addition to low-dose cytarabine 20 mg/m2 subcutaneously, QD Days 1-10 of each 28 day cycle, beginning cycle 1, day 1. Treatment was continued until disease progression or unacceptable toxicity. Endpoints included: complete remission, complete remission with partial hematological recovery, time to first complete remission or complete remission with partial hematological recovery, median observed time in remission for those who achieved complete remission, or stem cell transplantation.

Efficacy was established based on the rate of CR and the duration of CR.

AML=acute myeloid leukemia; CLcr=creatinine clearance; ECOG=Eastern Cooperative Oncology Group; IV=intravenous; QD=once a day.

*All patients received TLS prophylaxis and were hospitalized for monitoring during the ramp-up.

CR was defined as absolute neutrophil count (ANC) >1,000/microliter, platelets >100,000/microliter, red blood cell transfusion independence, and bone marrow with <5% blasts. Absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease.

CRh was defined as <5% of blasts in the bone marrow, no evidence of disease, and partial recovery of peripheral blood counts (platelets >50,000/microliter and ANC >500/microliter).

See baseline characteristics

See remission rates

See analysis in mutational and cytogenetic risk subgroups