Low-dose azacitidine plus venetoclax demonstrates tolerability and feasibility as maintenance therapy in acute myeloid leukemia (AML), according to findings from a phase 2 trial presented at the 2022 American Society of Hematology (ASH) Annual Meeting & Exposition.

These findings were presented by lead author, Alexandre Bazinet, MD, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston., who explained that “the combination of azacitidine and venetoclax is synergistic and highly effective in AML.”

This phase 2 study aimed to assess the combination of low-dose azacitidine plus venetoclax as a maintenance regimen in this setting. Patients were eligible for enrollment if they had a diagnosis of AML not immediately eligible for stem cell transplant and had achieved a first complete remission (CR) or CR with incomplete hematologic recovery (CRi) following ≥2 cycles of intensive chemotherapy (cohort 1) or low-intensity therapy (cohort 2).

The primary end point of the study was relapse-free survival (RFS), defined as enrollment to relapse or death, whichever occurred first. Secondary end points included (OS), minimal residual disease (MRD) clearance rates, and safety/toxicity.

A total of 34 patients were enrolled: 25 in cohort 1 and 9 in cohort 2. Patients were treated with azacitidine at 50 mg/m² intravenously or subcutaneously on days 1 to 5 plus venetoclax 400 mg orally on days 1 to 14, every 28 days, for up to 24 cycles. Venetoclax duration could be reduced to 7 days in patients at high risk for cytopenias.

The median follow-up was 13.3 months. Overall, 19 (76%) patients had been previously exposed to venetoclax as part of their induction regimen. During cycle 1, 21 (62%) patients received 7 days of venetoclax and 13 (38%) received 14 days of venetoclax. The median number of cycles given was 9.5 (range 1-24).

Median RFS was not reached (NR) in cohort 1 (70% at 12 months) and NR in cohort 2 (58% at 12 months). In addition, median OS was NR in cohort 1 (95% at 12 months) and NR in cohort 2 (63% at 12 months).

At enrollment, 7 patients were MRD-positive. Of these patients, 2 (29%) converted to MRD-negative while on maintenance therapy. The MRD-positive patients had a high incidence of adverse prognostic factors. Overall, 3 MRD-positive went off study to receive SCT and remain in remission. The 4 remaining MRD-positive patients have relapsed after 1.9, 2.5, 4, and 6 months, respectively.

The most common grade 3/4 adverse events were thrombocytopenia (21%), infections (21%), neutropenia (18%), and neutropenic fever (6%). A total of 4 patients (12%) required venetoclax dose reductions at cycle 2 for cytopenias and 7 (21%) patients died after relapse of AML or from SCT complications.

With over 13 months of follow-up, this was the first experience demonstrating the tolerability and feasibility of low-dose azacitidine plus venetoclax as maintenance therapy in AML. In conclusion, “RFS and OS are encouraging, especially in the non-adverse risk ELN categories (favorable or intermediate),” Dr Bazinet and coauthors concluded, “Further studies are needed to improve maintenance strategies in patients with ELN adverse or MRD-positive disease.”

Source:

Bazinet A, Kantarjian H, Borthakur G, et al. A Phase II Study of Azacitidine Plus Venetoclax As Maintenance Therapy in Acute Myeloid Leukemia: Durable Responses with Longer Term Follow-up. Presented at the ASH Annual Meeting & Exposition; December 10-13, 2022; New Orleans, LA, and virtual. Abstract 4059.