Venetoclax and azacitidine compared with intensive chemotherapy for adverse-risk acute myeloid leukemia patients receiving allogeneic hematopoietic stem cell transplantation in first complete remission: A multicenter study of TROPHY group.

Objective: Adverse-risk acute myeloid leukemia (AML) patients should receive allogeneic hematopoietic stem cell transplantation (allo-HSCT) at first complete remission (CR1). However, the influence of prior therapies [i.e., venetoclax plus azacitidine (VEN-AZA) or intensive chemotherapy (IC)] on post-transplant outcomes remains inconclusive. This multicenter, retrospective study compared the post-transplant outcomes between patients receiving VEN-AZA and those receiving IC before allo-HSCT.

Methods: This study was based on the transplant database of TROPHY group. Consecutive adverse-risk AML patients receiving allo-HSCT from January 2021 to June 2023 were screened in five Chinese transplant centers. Patients were categorized into VEN-AZA group if they received venetoclax combined with azacitidine as first-line therapy followed by allo-HSCT. Patients who received first-line therapy consisting of a mainstay treatment of cytarabine and anthracycline followed by allo-HSCT were categorized into IC group.

Results: In the total cohort, the 3-year probabilities of overall survival, leukemia-free survival, and event-free survival were better in the IC group than VEN-AZA group, particularly for patients with ASXL1 mutations or SF3B1 mutations. However, the survival of the VEN-AZA group was not superior to that of IC group in patients aged ≥55 years or those with the hematopoietic cell transplantation-comorbidity index scores ≥1 before allo-HSCT. After propensity score matching (median age: VEN-AZA group: 57 years; IC group: 55 years), only the probability of overall survival for the IC group was better than that of VEN-AZA group (93.6% vs. 78.0%, P=0.034) at the 1-year follow-up; however, all of the other clinical outcomes were comparable between the VEN-AZA and IC groups. The TP53 mutation was independently associated with post-transplant relapse and survival.

Conclusions: Our results suggest that IC remains the cornerstone of therapy, whereas VEN-AZA may also be used in younger patients and medically fit patients with adverse-risk AML who are receiving allo-HSCT in CR1.