Third-Generation Anti-CD30 CAR T-Cell Therapy Shows Durable Responses in Relapsed or Refractory CD30-Positive Lymphoma

Clinical Summary:

• Design/Population: This single-arm, multicenter, phase 1/2 trial evaluated third-generation anti-CD30 CAR T-cell therapy following fludarabine/cyclophosphamide lymphodepletion in patients with relapsed or refractory CD30-positive lymphoma, including patients with Hodgkin lymphoma.
• Key Outcomes: Anti-CD30 CAR T-cell therapy achieved a 95.5% overall response rate, with 3-year progression-free and overall survival rates of 74.2% and 79.0%, respectively. Consolidative autologous stem cell transplant was associated with deeper remissions and significantly longer survival.
• Clinical Relevance: Third-generation anti-CD30 CAR T-cell therapy produced depp and durable responses in heavily treated relapsed or refractory CD30-positive lymphoma, while consolidation with autologous stem cell transplant was associated with deeper remissions and significantly longer survival, suggesting a potential strategy for extending disease control after CAR T-cell therapy that warrants prospective confirmation.

Results from a phase 1/2 trial showed that third-generation anti-CD30 CAR T-cell therapy achieved a 95.5% objective response rate (ORR) and durable long-term disease control in patients with relapsed or refractory CD30-positive lymphoma, with improved outcomes observed among patients who subsequently underwent consolidative autologous stem cell transplant. 

This single-arm trial enrolled 44 patients with relapsed or refractory CD30-positive lymphoma, including 33 patients with Hodgkin lymphoma. Patients received lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by an infusion of third-generation anti-CD30 CAR T cells. The primary end points were safety and ORR. Key secondary end points included progression-free survival (PFS) and overall survival (OS).

Following CAR T-cell therapy, 23 patients achieved a complete response and 19 achieved a partial response, corresponding to a complete response rate of 52.3% and an ORR of 95.5%. During follow-up, the best ORR remained 95.5%, while 27 patients ultimately achieved a complete response, increasing the complete response rate to 61.4%. 

At a median of 3 months following CAR T-cell therapy, 24 patients underwent autologous hematopoietic stem cell transplant. The best complete response rate as 75% among patients who received CAR T-cell therapy followed by autologous hematopoietic stem cell transplant compared 45% with those who received CAR T-cell therapy alone. Patients who underwent consolidative autologous hematopoietic stem cell transplant also had significantly longer OS and PFS, although the provided data do not report hazard ratios or other effect estimates for these comparisons.

At 3 years, the OS rate for all patients was 79%, and the PFS rate was 74.2%. 

Hematologic toxicity was the predominant safety concern with grade ≥3 neutropenia occurring in 68.2% of patients. Cytokine release syndrome occurred in 40.9% of patients, including grade ≥3 events occurring in 4.5% of patients. 

“Third-generation anti-CD30 CAR-T demonstrates high efficacy and a favorable safety profile,” concluded study authors. “[The] addition of [autologous hematopoietic stem cell transplant] following CAR T-cell therapy improves depth of remission and potentially enhances OS and PFS.”

Source:

Wang X, Zhang Q, Yan D, et al. Long-term follow-up of third generation anti-CD30 CAR T-cell therapy in relapsed/refractory CD30+ lymphomas: A single-arm, multicentre, phase 1-2 trial. Clin Cancer Res. Published online: July 22, 2026. doi: 10.1158/1078-0432.ccr-26-1292