Immune reconstitution after CD7 CAR‐T cell therapy for refractory/relapsed acute T‐lymphoblastic leukaemia/lymphoblastic lymphoma (R/R T‐ALL/LBL)

Summary CD7 Chimeric Antigen Receptor‐T cell (CAR‐T) therapy demonstrates efficacy in relapsed/refractory (R/R) acute T‐lymphoblastic leukaemia (ALL)T‐ALL/lymphoblastic lymphoma (LBL), but concerns about T‐cell depletion and severe immunodeficiency persist. We compared infection rates and immune cell subsets in 60 R/R T‐ALL/LBL patients receiving naturally selected CD7 CAR‐T (NS7CAR‐T) with 60 R/R B‐ALL patients undergoing CD19 CAR‐T. Infections were monitored from infusion until allogeneic haematopoietic stem cell transplantation (HSCT) or up to 3 months. Overall infection rates did not significantly differ between groups (36.67% vs. 24.56%, p = 0.24), although the incidence of early immune effector cell‐associated haematotoxicity (ICAHT) grade III–IV was higher in the CD7 CAR‐T group than in the CD19 CAR‐T group (33.9% vs. 16.7%, p = 0.03). Post‐CD7 CAR‐T infusion analysis showed a significant decline in CD7(+) T cells and an increase in non‐CAR‐T‐derived CD7(−) T cells, particularly non‐CAR‐T cells, which rose to a median proportion of 84.4% (range: 22.1%–99.9%) by day 28; meanwhile, CD7(−) natural killer (NK) cells approached nearly 100% following the depletion of CD7(+) NK cells. This study indicates that while CD7 CAR‐T therapy significantly reduces CD7(+) T cells, it does not lead to increased short‐term infection rates. The notable expansion of non‐CAR‐T‐derived CD7(−) T and NK cells helps preserve immune function, highlighting distinct therapeutic mechanisms between CD7 CAR‐T and CD19 CAR‐T due to their different lineage restrictions.