A Successful Bridge Therapy Combining Hypomethylating Agents with Venetoclax for Adult Patients with Newly Diagnosed or Relapsed/Refractory Acute Myeloid Leukemia

SIMPLE SUMMARY: The introduction of venetoclax (VEN) to combination regimens has dramatically changed the paradigm of treatment for acute myeloid leukemia (AML) patients deemed unfit for intensive chemotherapy. Several researchers have reported that this regimen was successfully used as a bridge to potentially curative allogeneic hematopoietic stem cell transplantation (allo-HCT) in AML patients; however, data about clinical outcomes after allo-HCT are still lacking. In this study, we evaluated the post-transplant outcomes of 50 patients who received VEN-hypomethylating agents (HMA) treatment, either as initial therapy for newly diagnosed AML (n = 10) or as a salvage regimen for relapsed/refractory (R/R) AML (n = 40). The probabilities of overall survival, relapse-free survival, cumulative incidence of relapse, and nonrelapse mortality at 1 year were 63.7%, 59.3%, 28.5%, and 12.2%, respectively. Even though 30% of our data were from a second allo-HCT, our results suggest that allo-HCT following VEN-HMA therapy is a safe and effective treatment option. ABSTRACT: Recently, the combination of VEN-HMA has been shown to achieve durable responses in patients with both newly diagnosed (ND) and R/R-AML. We retrospectively evaluated the post-allo-HCT outcomes of 50 patients who received VEN-HMA therapy. In total, 10 were ND and 40 were R/R and, at the time of HCT, the median age was 53 years. In the ND- and R/R-AML groups, the percentage of patients who achieved CR/CRi or MLFS was 90% and 92.5%, respectively. In all, after a median follow-up of 13.7 months, the probabilities of overall survival (OS), relapse-free survival (RFS), cumulative incidence of relapse (CIR), and nonrelapse mortality (NRM) at 1 year were 63.7%, 59.3%, 28.5%, and 12.2%, respectively. In addition, the cumulative incidences of grade II–IV acute graft-versus-host disease (GVHD) and moderate–severe chronic GVHD at 1 year were 28.4% and 37.4%, respectively. In multivariate analysis, the factors associated with a statistically significant impact on OS were VEN-HMA cycle (p = 0.021), ELN risk group (p = 0.041), and the response to VEN-HMA therapy before allo-HCT (p = 0.003). Although 80% of our patients had R/R-AML and 30% underwent a second allo-HCT, our data still suggest that allo-HCT following VEN-HMA therapy is a safe and effective treatment option.