High efficacy and safety of anti-CD30 CAR-T cell therapy in refractory or relapsed CD30+ lymphoma patients

CAR-T cells therapy has good tolerability and effects in patients with Hodgkin lymphoma (HL) and anaplastic large cell lymphomas (ALCL). However, the second-generation CARs with either CD28 or 4-1BB costimulatory domains did not have an ideal rate of complete response.In this study, we developed a novel third-generation CAR against CD30 and investigated the efficacy and safety in patients with CD30 positive relapsed or refractory(r/r) lymphoma. We found that the anti-CD30 CAR-T cells specifically homing to the tumor with powerful anti-tumor activity in the tumor xenografts. Subsequently, we conducted a pilot study to evaluate the safety and feasibility of anti-CD30 CAR-T cells in 14 patients with r/r HL or anaplastic lymphoma kinase (ALK)-negative (ALK-) ALCL. The third-generation anti-CD30 CAR-T cells had superior expansion and longer persistence , and the CAR copies could be detected after CAR-T infusion for half a year. Of Thirteen patients (92.9%) were successes responded and ten patients (71.4%) achieved complete remission (CR) for 10 months and four patients remained in CR longer than two years in 5 patients who followed over two years. Our results showed that cytokine release syndrome (CRS) occurred in eleven patients but was mild, only one patient developed grade 3 CRS, and the other 10 patients developed grade 1 or 2 CRS who did not require anti-IL6 therapy. And no patient experienced neurotoxicity after infusion. Thus, anti-CD30 CAR-T cells are safety and effective way for treating relapsed/ refractory HL and ALCL patients.