New Efficacy, Safety Data Presented on BCL-2 Inhibitor Plus Azacitidine in AML

A recent phase Ib/II study evaluated lisaftoclax plus azacitidine in patients with acute myeloid leukemia (AML). Study authors presented their findings at the 2024 American Society of Clinical Oncology Annual Meeting.

“Our data support an emerging role for this new [B-cell lymphoma 2] inhibitor lisaftoclax combined with azacitidine for the treatment of elderly or unfit [treatment-naive] and relapsed or refractory AML patients, especially with low early mortality and promising median [progression-free survival (PFS)],” wrote the study authors.

The enrolled population of 76 patients with AML had a median age of 66 years and was 61.8% male. Thirty-nine patients were treatment-naive and aged 75 years or older or unfit, and 37 patients were adults with relapsed or refractory disease.

The patients received oral lisaftoclax in 400 mg, 600 mg, or 800 mg doses once daily in 28-day cycles, combined with azacitidine administered at 75 mg/m²/day for the first seven days.

Regarding the efficacy of the combination, patients with treatment-naive AML achieved an overall response rate (ORR) of 64.1% and a composite complete remission (CRc) rate of 51.3%.

In patients who received 600 mg lisaftoclax, the median duration of treatment achieved was 3.3 months and the median time to CRc was 1.9 months, though median PFS was not reached.

Patients with relapsed or refractory AML on the regimen achieved an ORR of 72.7% and a CRc rate of 45.5%. In patients who received 600 mg lisaftoclax, an ORR of 76.7% and a CRc rate of 50.0% was achieved, as well as a median duration of treatment of 3.8 months, median time to CRc of 2.5 months, median PFS of 10.2 months, and median overall survival of 14.7 months.

All patients who received the regimen reported experiencing treatment-emergent adverse events (AEs). Neutropenia occurred in 60.5% of patients, thrombocytopenia in 60.5%, diarrhea in 42.1%, hypokalemia in 40.8%, pyrexia in 35.5%, and vomiting in 30.3%. 89.5% of patients reported having grade 3 or 4 AEs and 43.4% reported having serious AEs. There were no occurrences of tumor lysis syndrome. The calculated 30-day mortality rate was 1.3% and the 60-day mortality rate was 3.9%.

The investigators determined 600 mg as the recommended phase II dose for lisaftoclax. They mentioned that “[a] phase III, randomized, double-blind clinical study is in progress to determine whether lisaftoclax plus azacitidine improves overall survival in elderly or unfit pts with AML.”

Reference

Wang H, Wei X, Liang Y, et al. Safety and efficacy of lisaftoclax, a novel BCL-2 inhibitor, in combination with azacitidine in patients with treatment-naïve or relapsed or refractory acute myeloid leukemia. Abstract #6541. Presented at the 2024 ASCO® Annual Meeting; May 31-June 4, 2024; Chicago, Illinois.