HMA/Venetoclax Showed Promise as Salvage Therapy for Relapsed AML and MDS After Allogeneic Stem Cell Transplant

The combination of hypomethylating agents (HMAs) and venetoclax demonstrated encouraging response rates and manageable safety outcomes for patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) who experience relapse after allogeneic hematopoietic stem cell transplant (alloHSCT), even among those with prior HMA/venetoclax exposure, in a retrospective analysis.

Outcomes for patients with AML and MDS who experience relapse after alloHSCT are poor.¹ The retrospective study presented by Diana T. Samuels, PharmD, BCOP, City of Hope National Medical Center, South Pasadena, California, was designed to investigate the efficacy and safety of HMA/venetoclax for these patients.²

The study included 84 participants treated between March 2017 and December 2023, with a median age of 64 years, who had received a median of two HMA/venetoclax cycles; nearly 55% had prior exposure to this regimen.

Complete response (CR) or CR with incomplete hematologic recovery (CRi) was achieved in 47% of participants with AML, with more than half achieving measurable residual disease (MRD) negativity. In participants with MDS, 57% achieved CR or CRi, with the majority achieving MRD negativity. Prior HMA/venetoclax exposure did not significantly affect response rates. Overall survival rates at six and nine months were 53% and 43% in the overall population, 50% and 40% in participants with AML, and 73% and 63% in participants with MDS. Median overall survival was 5.6 months for participants with AML and 9.6 months for those with MDS.

Neutropenia was reported in nearly all participants (99%), and grade 3/4 neutropenia was common but manageable. The mortality rate within 30 days of therapy initiation was 5%, with bacterial infections as the primary cause.

Dr. Samuels concluded: “For patients with AML and MDS who relapse after alloHCT, HMA/venetoclax seems an effective and well-tolerated salvage regimen, and HMA/venetoclax exposure before transplant does not affect efficacy.” Further research is needed to identify optimal post-treatment strategies and predictors of response to improve outcomes in this high-risk population.

1. Webster JA, Luznik, and Gojo I. Front Oncol. 2021;11:812207. doi: 3389/fonc.2021.812207
2. Samuels DT, Ball, BJ, Tsai N, et al. Outcomes of hypomethylating agents/venetoclax (HMA/VEN) treatment for relapse of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) after allogeneic hematopoietic cell transplant (alloHCT). Abstract #4935. Presented as the American Society of Hematology Annual Meeting; December 7-10, 2024; San Diego, California.