Anti-PD-1 Therapy Enhances the Efficacy of CD30-Directed Chimeric Antigen Receptor T Cell Therapy in Patients With Relapsed/Refractory CD30+ Lymphoma.

ABSTRACT

Anti-CD30 CAR-T is a potent candidate therapy for relapsed/refractory (r/r) CD30+ lymphomas with therapy limitations, and the efficacy needed to be further improved. Herein a multi-center phase II clinical trial (NCT03196830) of anti-CD30 CAR-T treatment combined with PD-1 inhibitor in r/r CD30+ lymphoma was conducted. After a lymphocyte-depleting chemotherapy with fludarabine and cyclophosphamide, 4 patients in cohort 1 and 3 patients in cohort 2 received 106/kg and 107/kg CAR-T cells, respectively, and 5 patients in cohort 3 received 107/kg CAR-T cells combined with anti-PD-1 antibody. The safety and the efficacy of CAR-T cell therapy were analyzed. Cytokine release syndrome (CRS) was observed in 4 of 12 patients, and only 1 patient (patient 9) experienced grade 3 CRS and was treated with glucocorticoid and tocilizumab. No CAR-T-related encephalopathy syndrome was observed. Only two patients in cohorts 2 and 3 experienced obviously high plasma levels of IL-6 and ferritin after CD30 CAR-T cell infusion. The overall response rate (ORR) was 91.7% (11/12), with 6 patients achieving complete remission (CR) (50%). In cohorts 1 and 2, 6 patients got a response (85.7%), with 2 patients achieving CR (28.6%). In cohort 3, 100% ORR and 80% CR were obtained in 5 patients without ≥3 grade CRS. With a median follow-up of 21.5 months (range 3-50 months), the progression-free survival and the overall survival rates were 45 and 70%, respectively. Of the 11 patients who got a response after CAR-T therapy, 7 patients (63.6%) maintained their response until the end of follow-up. Three patients died last because of disease progression. Taken together, the combination of anti-PD-1 antibody showed an enhancement effect on CD30 CAR-T therapy in r/r CD30+ lymphoma patients with minimal toxicities.