Safety and Efficacy of Venetoclax Combined with Hypomethylating Agents or Low-Dose Cytarabine for Acute Myeloid Leukemia before and after Allogeneic Hematopoietic Cell Transplantation

Introduction Venetoclax combined with hypomethylating agents (HMA) or low-dose cytarabine (LDC) has emerged as a promising therapy for acute myeloid leukemia (AML). However, there are scarce data on the use of this drug in the context of allogeneic hematopoietic cell transplantation (allo-HCT). We thus report a case series of patients using venetoclax-based therapy for AML prior to or after allo-HCT. Methods Adult patients with active AML receiving venetoclax + HMA/LDC before allo-HCT as bridge therapy or following HCT as salvage therapy were included in this report. Cases were treated at five different Brazilian centers from Jun’18 to Jul’19. Patients rescued with venetoclax-containing regimens as bridge therapy to allo-HCT were included regardless of whether they managed to undergo the procedure or not. Results We retrieved 16 patients meeting the inclusion criteria. Median age was 45 years old (range 23-83). Eight (50%) patients were male. Median follow-up time was 4 months (1.1-9.1). Ten patients had de novo AML, four secondary AML, and two therapy-related AML. Three patients were treatment-naive and thirteen had relapsed/refractory disease, including five cases of post-allo-HCT relapse. Relapsed/refractory AML patients had a median of two previous lines of treatment (1-4). Venetoclax was given with azacitidine (n=4), decitabine (n=7) or LDC (n=5). Patients received a median of two cycles of venetoclax-based therapy (1-6), and the most common toxicity was neutropenia. Fourteen evaluable patients achieved complete response (CR) or complete response with incomplete count recovery (CRi) after a median time of 38 days (23-158). Of those receiving venetoclax-based bridge therapy to allo-HCT, 9/11 patients underwent allo-HCT after achieving CR/CRi, including 7 AML patients bearing chemorefractory disease or high-risk cytogenetics. Two patients died after allo-HCT, one from AML relapse and the other from infectious complications; all the other seven patients had full engraftment and were alive with no active GVHD at last follow-up. Two did not receive the allo-HCT, one because of relapsed AML prior to transplant and the other because of death by septic shock. Five cases of post-allo-HCT AML relapse received venetoclax-based therapy. Three of them also received donor lymphocyte infusions (DLI). Four evaluable patients achieved CR/CRi. There were two deaths: one from disseminated herpes simplex virus and one from septic shock. There were two cases of grade 3-4 acute GVHD, yet both of them responded to steroids and were possibly related to concomitant DLI. Conclusion Despite the limited number of patients and short follow-up time, therapy including venetoclax seems to be safe and yield encouraging results before and after allo-HCT, even in heavily treated AML patients. These data support future clinical trials incorporating venetoclax-based therapy into the allo-HCT setting.