ALL-220 Azacitidine in Combination With Venetoclax Maintenance Post Allogeneic Hematopoietic Cell Transplantation in T-Cell Acute Lymphoblastic Leukemia

Abstract

Relapsed and/or refractory (R/R) T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease with few available salvage options and usually carries a dismal outcome with only 10% of patients surviving at 5 years. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) efficacy in R/R T-ALL remains problematic, as up to half of patients will relapse post allo-HSCT. Post-transplant maintenance in acute myeloid leukemia (AML) has long been debated, with recent implementation by transplant centers, especially the use of hypomethylating agents (HMAs) and targeted agents such as FLT3 inhibitors. In T-ALL, this concept has not been explored yet with very little data. The aim of this case series is to present a novel approach for post-transplant maintenance in patients diagnosed with R/R T-ALL. This is a case series including 4 patients with R/R T-ALL who underwent allo-HSCT at the American University of Beirut Medical Center and received post-transplant maintenance with low-dose 5-azacitidine and venetoclax. We identified four adult patients diagnosed with high-risk T-ALL (three patients with mature T-ALL and one with early T-precursor [ETP] ALL) with a median age of 35 years (range, 31-45 years). All received post-allo-HSCT maintenance with 5 days of low dose 5-azacitidine at 32 mg/m2 daily with venetoclax 100 mg orally daily for 5 days with voriconazole every 28 days. The median duration of maintenance treatment was 12.75 months (range, 9.5-23.5 months). All patients remain in continuous complete remission with undetectable measurable residual disease after a median follow-up of 15 months from the date of allo-HSCT (range, 12-25 months). Both HMAs and venetoclax possess significant antitumor activity effects against AML/myelodysplastic syndrome, and their efficacy in R/R T-ALL has been demonstrated in multiple case series. These encouraging results along with our case series of successful maintenance treatment with azacitidine with venetoclax in T-ALL are worth exploring in larger prospective trials.