Encouraging Efficacy Seen with Post-Transplant Venetoclax, Azacitidine Maintenance for Acute Leukemia

Maintenance therapy with venetoclax plus azacitidine may be a good option after hematopoietic stem cell transplantation (HSCT) in patients with high-risk acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL), according to data presented at the 2022 American Society of Hematology Annual Meeting.

Betul Oran, MD, of the University of Texas MD Anderson Cancer Center, and colleagues explained that transplant is the only potentially curative option in patients with acute leukemia; however, patients with high-risk disease often have inferior outcomes. Existing data on maintenance therapies are conflicting.

This single-center study was designed to test maintenance venetoclax plus azacitidine after transplant. The study enrolled 30 patients with high risk AML, B-cell ALL, T-cell ALL, or mixed phenotype leukemia. Patients were treated with up to 12 cycles of the combination. Venetoclax dosing could be adjusted.

Of the 30 included patients, 27 had AML and 3 had ALL. About half (48%) were in complete remission at HSCT, and the majority (63%) had received a myeloablative intensity conditioning regimen using intravenous busulfan.

With a median follow-up of 8.67 months, the median recurrence-free and overall survival were not yet reached. Estimated one-year recurrence-free survival was 69.2%, with an estimated one-year overall survival of 90.2%. These survival estimates were “highly encouraging compared to the historical outcomes for this high-risk group of patients”, the researchers wrote.

The researchers also attempted to estimate the mean number of grade ≥3 treatment-related adverse events per patients These estimates were 1.87 for decreased white blood cell count, 1.68 for decreased absolute neutrophil count, 1.06 for decrease platelet count, 0.55 for anemia, 0.13 for pneumonia, and 0.06 for each event of febrile neutropenia, maculopapular rash, respiratory failure and secondary graft failure.

Thirty percent of patients required venetoclax dose reduction due to frequent and prolonged myelosuppression. This combined with treatment delays between cycles highlighted “the importance of monitoring these patients very closely,” the researchers wrote.

Reference

Oran B, Champlin RE, Thall PF, et al. Phase II trial of venetoclax (ven) in combination with azacitidine (AZA) as maintenance therapy for high-risk acute leukemia following allogeneic stem cell transplantation (SCT). Abstract #4738. Presented at the 64th American Society of Hematology Annual Meeting, December 10-13, 2022; New Orleans, Louisiana.