Donor-derived CD7 CAR T cells for pediatric and adult relapsed/refractory T-ALL/LBL: a phase 2 trial Available to Purchase

• Donor-derived CD7 CAR T appears effective in inducing complete remission in r/r T-ALL/LBL.

• Late-onset adverse events after CD7 CAR T can be serious, although consolidatory transplantation may lower the risks of some fatal events.

This phase II trial assessed CD7 CAR T-cells derived from previous transplant or newly HLA-matched donors for relapsed/refractory T-cell acute lymphoblastic leukemia/lymphoma. It was designed to enroll 70 patients but terminated early, with 55 ultimately treated, due to discontinuation of departmental operations. Within three months, 89% (n=49) achieved best overall response of partial remission or better. 19 received stem-cell transplantation (SCT) at a median 1.3 months (range 1.0-10.6). After a 26.3-month median follow-up, median event-free survival was 5.0-months (95% CI: 4.1-8.4) with median 8.5-month overall survival (95% CI: 6.1-15.6). No deaths occurred in first 30 days; adverse events (AEs) included cytokine release syndrome in 87% (n=48) at grades 1-2 and 11% (n=6) at grade 3, neurotoxicity in 9% (n=5) at grade 1. Graft-versus-host disease (GVHD) was in 38% (n=21) at grades 1-2 and 2% (n=1) at grade 3. Grade 1-2 infections occurred in 29% (n=16). Cytopenias in 4% (n=2) at grades 1-2 and 96% (n=53) at grades 3-4. After 30 days, grade 3-5 AEs included cytopenias (grade 3 in 24%, grade 4 in 67%), infections (grade 3 in 9%, grade 4 in 5%, grade 5 in 9%), GVHD (grade 3 in 4%, grade 5 in 4%), thrombotic microangiopathy (grade 5 in 4%), and hepatic failure (grade 5 in 2%). 20% (n=11) encountered non-relapse mortality after 30 days, accounting for 35% of responders without consolidatory SCT. While effective at inducing remission, death in remission beyond 30 days is a concern. NCT04689659