The use of venetoclax‐based salvage therapy for post‐hematopoietic cell transplantation relapse of acute myeloid leukemia
Michael Byrne, Nathalie Danielson, Salyka Sengsayadeth, Adrianne Rasche, Katie Culos, Katie S. Gatwood, Houston Wyatt, Wichai Chinratanalab, Bhagirathbhai Dholaria, P. Brent Ferrell, Kristin Fogo, Stacey Goodman, Madan Jagasia, Reena Jayani, Adetola A. Kassim, Sanjay Mohan, Bipin N. Savani, Stephen A. Strickland, Brian G. Engelhardt, Michael R. Savona
Abstract
For patients with high risk myeloid disease, allogeneic hematopoietic cell transplantation (HCT) is the only potentially curative therapy. Unfortunately, many of these patients relapse after HCT and have a limited survival. The recent approval of venetoclax, an orally bioavailable BCL-2 inhibitor, resulted in significant responses in treatment naïve acute myeloid leukemia (AML), and off-label use in the relapsed/refractory setting is increasing. We report the outcomes of 21 patients who underwent allogeneic HCT for myeloid disease, relapsed with AML, and were treated with venetoclax. Several patients had poor risk features including antecedent hematologic malignancy (6/21), complex karyotype (6/21), and TP53 mutations (5/21). The median age was 64.5 years and time from HCT to relapse was 5.7 months (range: 0.9 to 44.9 months). Of the 19 patients who were assessed for response, there were meaningful treatment responses seen in eight patients: five CR, three CRi, zero PR, for an ORR of 42.1%. Treatment effect was seen in six additional patients, including four in the morphologic leukemia-free state. Nine patients maintained their response for ≥3 months and eight were receiving therapy at data cut. Post-HCT AML relapse has an exceedingly poor outcome, and venetoclax-based therapy is a potent therapy option that should be studied prospectively in this setting.