CELL INTELLIGENCE · 肿瘤细胞治疗研究

INTRODUCTION: Although CD30-directed chimeric antigen receptor (CAR)-T cell therapy has demonstrated antitumor activity in CD30+ lymphomas, its therapeutic efficacy remains suboptimal. We therefore conducted a prospective, phase II, single-arm, multicenter clinical trial (ChiCTR-2100046763) to evaluate the efficacy and safety of CD30 CAR-T cell therapy in combination with camrelizumab, an immune checkpoint inhibitor, in patients with relapsed/refractory (r/r) CD30+ lymphomas. METHODS: All participants received a lymphodepleting regimen followed by infusion of CD30 CAR-T cells at a dose of 1 107 cells/kg. Camrelizumab was subsequently administered on a scheduled basis starting 15 days after CAR-T infusion and continued until unacceptable toxicity or disease progression. RESULTS: A total of 18 patients were enrolled, of whom 12 (66.7%) completed the CD30 CAR-T infusion, including eight with classical Hodgkin lymphoma (cHL) and four with T-cell lymphomas. Among 11 efficacy-evaluable patients, the best objective response rate (ORR) was 63.6%, including four complete responses (CR, 36.3%). After a median follow-up of 30.8 months, the median overall survival (OS) was not reached, and the median progression-free survival (PFS) was 11.1 months (95% CI, 0 26.2). In the subset of seven cHL patients, the ORR and CR rates were 100.0% and 57.1%, with 2-year PFS and OS of 57.1% and 100.0%, respectively. Remarkably, five cHL patients who had previously failed PD-1 blockade still achieved an ORR of 100.0% and a CR rate of 40.0%; median OS was not reached, and median PFS was 15.0 months. In contrast, none of the four T-cell lymphoma patients achieved an objective response. Cytokine release syndrome occurred in eight patients (66.7%), all grade 1 2. The most frequent grade 3 4 toxicities were lymphopenia (58.3%) and neutropenia (41.7%). CONCLUSIONS: The combination of CD30 CAR T-cell therapy with camrelizumab demonstrated a favorable safety profile and elicited durable, clinically meaningful responses in patients with r/r cHL, including those who had failed prior PD-1 blockade. In contrast, although this regimen remained therapeutically well tolerated, its antitumor activity was limited in T-cell lymphomas, underscoring the need for alternative approaches or more effective combinatorial strategies in this disease context.