Long-term Follow-up of Third-generation Anti-CD30 CAR T-cell Therapy in Relapsed/Refractory CD30+ Lymphomas: A...

This report presents long-term outcomes of third-generation anti-CD30 chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed/refractory (r/r) CD30+ lymphoma.

In this single-arm, multicenter, phase I/II trial, patients received a lymphodepletion regimen comprising fludarabine and cyclophosphamide, followed by infusion of anti-CD30 CAR T cells. Primary endpoints included safety and overall response rate (ORR), whereas secondary endpoints were progression-free survival (PFS) and overall survival (OS).

Forty-four patients were enrolled, including 33 cases of Hodgkin lymphoma. Of 44 patients, 23 achieved complete response (CR) to CAR T, and 19 achieved PR, resulting in a CR rate of 52.3% and an ORR of 95.5%. The most frequent toxicities were hematologic adverse events of grade 3 or higher (68.2% of neutropenia). Cytokine release syndrome occurred in 18 (40.9%) patients, with 2 (4.5%) cases being ≥ grade 3. In the follow-up period, 24 patients underwent autologous hematopoietic stem cell transplantation (auto-HSCT) after CAR T within a median of 3 months. The best ORR was 95.5%, with 27 (61.4%) patients achieving CR. The best CR rate was higher in patients receiving CAR T followed by auto-HSCT compared with those receiving CAR T alone (75% vs. 45%). Three-year OS and PFS rates for all patients were 79% [95% confidence interval (CI), 66.1%-91.9%] and 74.2% (95% CI, 60.3% -88.1%), respectively. Patients receiving consolidated auto-HSCT following CAR T exhibited significantly longer OS and PFS compared with those treated with CAR T alone.

Third-generation anti-CD30 CAR T demonstrates high efficacy and a favorable safety profile in patients with r/r CD30+ lymphoma. Addition of auto-HSCT following CAR T-cell therapy improves depth of remission and potentially enhances OS and PFS.