Tisa-cel for post-HSCT relapse in children and young adults with B-ALL: A real-world study

Results from a retrospective, multicenter, real-world study evaluating tisagenlecleucel (tisa-cel) for post-hematopoietic stem cell transplantation (HSCT) relapse in 220 pediatric and young adult (≤25 years) patients with B-cell acute lymphoblastic leukemia (B-ALL) were published in Leukemia by Moser et al. Endpoints included overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS). 

Key data: At a median follow-up of 30.0 months, 2-year EFS was 43.6% and 2-year OS was 67.2%. Among patients who achieved complete remission (CR) at Day 28, 2-year RFS was 45.8%, and the 2-year cumulative incidence (CI) of CAR T-cell therapy failure was 57.1%. The 2-year CI of CAR T-cell therapy failure was higher among patients who had received a prior HSCT from a matched sibling donor (MSD) compared with those who had received a mismatched donor (MMD) or matched family/matched unrelated donor (MFD/MUD) (73.8% vs 52.2% vs 49.7%; p = 0.006). Early post-HSCT relapse (<6 months) was associated with a higher 2-year incidence of CAR T-cell therapy failure compared with late relapse (≥6 months; 69.3% vs 53.4%; p = 0.050). By disease status at lymphodepletion, the 2-year CI of CAR T-cell therapy failure was 43.9% among patients who were measurable residual disease (MRD)-negative, 52.2% among those who were MRD-positive, and 69.2% among those in non-remission (p = 0.003). 

Key learning: In this real-world study, prior HSCT from an MSD, early post-HSCT relapse, and higher disease burden at lymphodepletion were associated with a higher incidence of CAR T-cell therapy failure in pediatric and young adult patients with B-ALL who received tisa-cel for post-HSCT relapse. These findings support individualized treatment decisions for this patient population.