Low-dose CD7 chimeric antigen receptor T cells for relapsed/refractory T-cell lymphomas: single-arm, open-label, phase I study

CD7-directed chimeric antigen receptor (CAR)-T cell therapy has shown early efficacy in patients with refractory or relapsed T cell acute lymphoblastic leukemia (r/r T-ALL). However, manufacturing difficulties remain key challenges. We conducted a phase I study (ChiCTR2200058969) with 3 + 3 low dose-escalation followed by cohort expansion was designed in r/r T-cell lymphoma patients. CD7 CAR-T cells were isolated from patients or from previous stem-cell transplantation donors. The phase Ia study is being conducted with the following dose levels (DL): 1×10 ⁴ , 5×10 ⁴ , and 1×10 ⁵ (± 30%) CAR-T cells/kg. Of 40 patients enrolled, 31 received the recommended phase Ib dose of 1×10 ⁵ (± 30%) CAR-T cells/kg.The most common treatment-related adverse event (AE) within 30 days included cytokine release syndrome (CRS) (92.5%;5% grade 3–4), neutropenia (100%; 97.5% grade 3–4), thrombocytopenia (100%; 85% grade 3–4).In the Ib phase (n = 31), the ORR was 93.5% (29/31) and the CR rate was 80.6% (25/31). For responders in phase Ib (n = 29), patients who received allo-HSCT consolidation (n = 16) had superior 2-year OS compared to patients without allo-HSCT consolidation (n = 13) [54.1% (95% CI: 26.7–75.2) vs. 23.1% (95% CI:5.6–47.5) (P = 0.038)].low-dose CD7 CAR-T cell therapy is effective against r/r T-NHL, and allo-HSCT after achieving remission with CD7 CAR-T therapy can significantly prolong survival.