Azacitidine plus venetoclax effective, safe for certain patients with AML
Click Here to Manage Email Alerts
The addition of azacitidine to venetoclax significantly improved response rates and OS among certain patients with acute myeloid leukemia, according to study results presented at the virtual European Hematology Association Annual Congress.
The regimen also exhibited a manageable safety profile among these patients, who were ineligible for intensive therapy due to comorbidities or older age, researchers noted.
The addition of azacitidine to venetoclax significantly improved response rates and OS among certain patients with acute myeloid leukemia.
“Current therapy options for AML include standard induction therapy, which is typically intensive chemotherapy,” Courtney D. DiNardo, MD, MSCE, associate professor in the department of leukemia of the division of cancer medicine at The University of Texas MD Anderson Cancer Center, told Healio. “However, not all patients are able to tolerate the standard intensive chemotherapy, often because of age, abnormal organ function or comorbidities. There is such a need for effective therapies for patients who cannot withstand chemotherapy. Even with current therapies, the 5-year survival rate for patients with AML remains at approximately 29%.”
The FDA approved venetoclax (Venclexta; AbbVie, Genentech), an oral BCL-2 protein inhibitor, in combination with azacitidine, decitabine or cytarabine as a front-line treatment for older patients with AML who are unfit for induction chemotherapy.
In the randomized, phase 3, double-blind, multicenter trial, DiNardo and colleagues randomly assigned 431 patients with AML (median age, 76 years; range, 49-91) to azacitidine in combination with venetoclax (n = 286) or with placebo (n = 145).
Patients received subcutaneous or IV azacitidine dosed at 75 mg/m2 on days 1 to 7 of each 28-day cycle. Those in the venetoclax group received oral venetoclax dosed at 400 mg daily on days 1 to 28 with a 3-day ramp up to cycle one.
OS served as the primary endpoint. Secondary endpoints included rates of composite complete remission — defined as complete remission plus complete remission with incomplete count recovery — and EFS.
Patients received a median seven cycles (range, 1-30) of azacitidine in the venetoclax group and a median 4.5 cycles (range, 1-26) in the placebo group.
Median follow-up was 20.5 months.
Results, analyzed using the Kaplan-Meier method and compared between groups using the log-rank test stratified by age and cytogenetic risk, showed median OS of 14.7 months in the venetoclax group and 9.6 months in the placebo group (HR = 0.66; 95% CI, 0.52-0.85).
Rates of composite complete remission were 66.4% in the venetoclax group and 28.3% in the placebo group (P < .001).
Patients in the venetoclax group had a shorter median time to first complete response with or without incomplete count recovery (1.3 months vs. 2.8 months) and longer duration of composite complete remission (17.5 months vs. 13.4 months) than those in the placebo group.
Researchers observed higher response rates with the venetoclax combination among patients with poor cytogenetic risk (53% vs. 23%), intermediate cytogenetic risk (74% vs. 32%), de novo AML (66% vs. 30%) and secondary AML (67% vs. 23%).
Researchers also reported longer EFS in the venetoclax group (9.8 months; 95% CI, 8.4-11.8) compared with the placebo group (7 months; 95% CI, 5.6-9.5; P < .001).
Rates of 30-day mortality were 7% in the venetoclax group and 6% in the placebo group.
Grade 3 or greater hematological adverse events included thrombocytopenia (venetoclax, 45% vs. placebo, 38%), neutropenia (42% vs. 29%), febrile neutropenia (42% vs. 19%), anemia (26% vs. 20%) and leukopenia (21% vs. 12%).
Other common gastrointestinal adverse events included nausea (44% vs. 35%), constipation (43% vs. 39%), diarrhea (41% vs. 33%) and vomiting (30% vs. 23%).
“Venetoclax was granted accelerated approval in November 2018 by the FDA in combination with azacitidine, decitabine or low-dose cytarabine for the treatment of newly diagnosed AML in adults who are aged 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy,” DiNardo told Healio. “Positive results from [this trial] provide additional support for the clinical benefit of venetoclax in combination with azacitidine in patients with previously untreated AML.”
Collapse
DiNardo C, et al. Abstract LB2601. Presented at: European Hematology Association Annual Congress (virtual meeting); June 11-21, 2020.
Click Here to Manage Email Alerts