Venetoclax-Based Therapy as a Bridge to Hematopoietic Stem Cell Transplantation in Relapsed or Refractory Pediatric Acute Leukemia.

Abstract

Relapsed and/or refractory (R/R) pediatric acute leukemia carries a dismal prognosis, largely driven by chemoresistance to conventional salvage therapy. The BH3-mimetic venetoclax, combined with chemotherapy or hypomethylating agents, has demonstrated efficacy in small clinical trials. However, data on its role as a bridge to hematopoietic stem cell transplantation (HSCT) and on re-challenge in previously exposed patients remain limited. We report outcomes from 21 children treated with 26 episodes of venetoclax-based regimens as a bridge to HSCT, including five after prior venetoclax exposure. Overall response rate was 75% (15/20) after initial treatment and 100% (5/5) after re-treatment. Overall, 62% (16/26) of all patient-episodes facilitated immediate HSCT, and for another 12% (3/26), venetoclax-based therapy eradicated disease, and the patient transitioned to surveillance rather than HSCT. As such, venetoclax may represent an effective bridging strategy in R/R pediatric leukemia.