Venetoclax/Azacitidine, Intensive Chemotherapy Before HSCT Have Comparable Post-Transplant Outcomes For AML

Patients with acute myeloid leukemia (AML) who received a venetoclax/azacitidine combination prior to allogeneic hematopoietic stem cell transplantation (HSCT) had post-transplant outcomes comparable to patients treated with intensive chemotherapy before transplant.

The results of the study, led by Amanda Winters, MD, PhD, of the Center for Cancer and Blood Disorders at the University of Colorado, were published in Transplantation and Cellular Therapy.

Investigators retrospectively analyzed data from 169 patients at a single center who received allogeneic HSCT in their first remission after intensive chemotherapy or a venetoclax/azacitidine combination.

The study evaluated the depth of remission before allogeneic HSCT and outcomes after allogeneic HSCT in patients with non-relapse/refractory AML receiving pre-allogeneic-HSCT therapy with venetoclax/azacitidine or intensive chemotherapy.

Relapse-free survival and overall survival were similar between patients treated with venetoclax/azacitidine or intensive chemotherapy before transplant. The cumulative incidences of transplant-related mortality, relapse, and acute and chronic graft-versus-host disease were also comparable between treatment groups.

There was no difference in survival in younger (<65 years) and older (≥65 years) patients between the treatment groups.

Pre-allogeneic-HSCT measurable residual disease (MRD) as measured by clinical flow cytometry was significantly predictive of post-allogeneic HSCT relapse and survival in patients who received intensive chemotherapy before transplant. It was not significantly predictive of relapse or survival in patients who received venetoclax/azacitidine.

However, cytogenetics/fluorescence in situ hybridization MRD positivity before transplant was predictive of poor post-transplant outcomes for all patients.

The results of the analysis have clinical implications, as venetoclax-based regimens are the standard of care for patients with newly diagnosed AML who are “unfit” for intensive chemotherapy, and if these patients achieve remission, “they may also be considered for potentially curative consolidation” with allogeneic HSCT, the authors wrote.

“While these findings require prospective validation in a larger cohort of patients, they suggest that [venetoclax/azacitidine] followed by [allogeneic HSCT] is a reasonable management strategy for transplant candidates at any age,” the researchers concluded.

Winters AC, Bosma G, Abbott D, et al. Outcomes are similar following allogeneic hematopoietic stem cell transplant for newly diagnosed acute myeloid leukemia patients who received venetoclax + azacitidine versus intensive chemotherapy. Transplant Cell Ther. 2022. doi:10.1016/j.jtct.2022.07.022