Hematopoietic Cell Transplantation after CD19 Chimeric Antigen Receptor T Cell-Induced Acute Lymphoblastic Leukemia Remission Confers a Leukemia-Free Survival Advantage

Consolidative hematopoietic cell transplantation (HCT) after CD19 chimeric antigen receptor (CAR) T cell therapy is frequently performed for patients with refractory/ relapsed B cell acute lymphoblastic leukemia (B-ALL). However, there is controversy regarding the role of HCT following remission attainment. We evaluated the effect of consolidative HCT on leukemia-free survival (LFS) in pediatric and young adult subjects following CD19 CAR T cell induced remission. We evaluated the effect of consolidative HCT on LFS in pediatric and young adult subjects treated with a 41BB-CD19 CAR T cell product on a phase 1/2 trial, Pediatric and Young Adult Leukemia Adoptive Therapy (PLAT)-02 (ClinicalTrials.gov identifier NCT02028455), using a time-dependent Cox proportional hazards statistical model. Fifty of 64 subjects enrolled in PLAT-02 phase 1 and early phase 2 were evaluated, excluding 14 subjects who did not achieve remission, relapsed, or died before day 63 post-CAR T cell therapy. An improved LFS (P = .01) was observed in subjects who underwent consolidative HCT after CAR T cell therapy versus watchful waiting. Consolidative HCT improved LFS specifically in subjects who had no prior history of HCT, with a trend toward significance (P = .09). This benefit was not evident when restricted to the cohort of 34 subjects with a history of prior HCT (P = .45). However, for subjects who had CAR T cell functional persistence of 63 days or less, inclusive of those with a history of prior HCT, HCT significantly improved LFS outcomes (P = .01). These data support the use of consolidative HCT following CD19 CAR T cell-induced remission for patients with no prior history of HCT and those with short functional CAR T cell persistence.