Hypomethylating Agents Plus Venetoclax Regimen Post-Allogeneic Hematopoietic Cell Transplant Relapse for Patients With AML

The combination of hypomethylating agents plus venetoclax post-allogeneic hematopoietic cell transplant (alloHCT) relapse demonstrated efficacy among patients with acute myeloid leukemia (AML), with possibly better outcomes among patients with nucleophosmin 1 (NPM1) and isocitrate dehydrogenase (IDH) 1/2-mutated cases.

According to Filip Ionescu, MD, University of South Florida, Tampa, Florida, and coauthors, hypomethylating agent plus venetoclax is commonly known as a frontline combination for treating AML, “but its efficacy and safety in post-allogeneic hematopoietic cell transplant (alloHCT) relapse remain underexplored.” They added, “Outcomes have been poor for this population, with no standard treatment.” 

In order to expand the research on this combination, the study authors aimed to evaluate end points including rates of complete remission with or without hematologic recovery (CR/CRi) and minimal residual disease (MRD) negativity, duration of CR/CRi, and overall survival. A total of 72 patients with AML who were venetoclax-naive and received hypomethylating agents plus venetoclax at relapse post-alloHCT were retrospectively analyzed in this trial. Because of the larger sample size, the study authors also assessed the effect of cytogenetic/molecular features on the odds of CR/CRi. 

Study results indicated that among eligible patients, 48% (n = 32) achieved CR/CRi. MRD negativity was recorded in 10 of 12 patients. The study authors noted that NPM1 and IDH 1/2 mutations, as well as increasing the time from alloHCT to relapse, were associated with an increased chance of CR/CRi. Donor lymphocyte infusions or a second alloHCT were subsequently administered to 14 patients. Responses lasted for a median of 17.8 months. Patients who responded had a greater median overall survival of 19.7 months compared to 2.9 months among patients who did not respond. 

In terms of safety, treatment was well-tolerated. However, prolonged cytopenias commonly occurred and most patients needed reduction in the number of venetoclax days per cycle. 

Ionescu et al concluded, “These data support the efficacy of this combination in the alloHCT relapse setting where we report responses among nearly half of patients, with possibly greater benefit for NPM1 and IDH 1/2-mutated cases.”

“These responses can be durable and profound as evidenced by conversion to MRD negativity,” they added. 

Source: 

Ionescu F, David JC, Ravichandran A, et al. Hypomethylating agents and venetoclax for acute myeloid leukemia relapsed after hematopoietic stem cell transplant. Clin Lymph, Leuk & Myelom. Published online: February 12, 2024. doi: 10.1016/j.clml.2024.02.005