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Prophylactic maintenance with venetoclax/azacitidine after reduced intensity conditioning allo-transplant for high risk MDS and AML
Garcia, J. S., Kim, H. T., Murdock, H. M., Ansuinelli, M., Brock, J., Cutler, C. S., Gooptu, M., Ho, V. T., Koreth, J., Nikiforow, S., et al
Blood advances. 2024
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Abstract
We conducted a phase 1 trial assessing safety and efficacy of prophylactic maintenance therapy with venetoclax and azacitidine (Ven/Aza) in patients with high risk myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML) undergoing reduced intensity allogeneic hematopoietic stem cell transplantation following venetoclax and FluBu2-conditioning (Ven/FluBu2 allo-SCT) with tacrolimus and methotrexate as graft-versus-host disease (GVHD) prophylaxis. Among 27 patients who underwent Ven/FluBu2 allo-SCT (55.6% prior venetoclax exposure and 96% molecular measurable residual disease (MRD)-positive), 22 received maintenance therapy with azacitidine 36 mg/m2 intravenously on days 1-5 and venetoclax 400 mg by mouth on days 1-14 on one of two schedules (42-day cycles x 8 or 28-day cycles x 12). During maintenance, the most common grade 3/4 adverse events were leukopenia, neutropenia and thrombocytopenia, which were transient and manageable. Infections were uncommon (n=4, all grade 1-2). The 1-year and 2-year moderate/severe chronic GVHD rates were 4% (95% CI, 0.3-18%) and 22% (95% CI, 9-40%). After a median follow-up of 25-months among survivors, median overall survival (OS) was not reached. In the 22 patients who received Ven/Aza maintenance, the 2-year OS, progression-free survival, non-relapse mortality, and cumulative incidence of relapse rates were 67% (95% CI, 43-83%), 59% (95% CI, 36-76%), 0%, and 41% (95% CI, 20-61%), respectively. Immune monitoring demonstrated no significant impact on T cell expansion, but identified reduced B cell expansion compared to controls. This study demonstrates prophylactic Ven/Aza maintenance can be safely administered in high risk MDS/AML patients, but a randomized study is required to properly assess any potential benefit. (NCT03613532).