Autologous stem cell transplantation in tandem with Anti-CD30 CAR T-cell infusion in relapsed/refractory CD30+ lymphoma

• DOI: 10.1186/s40164-022-00323-9
• Publication Date: 2022-10-17T12:08:16Z
• Authors: Peiling Zhang; Xiuxiu Yang; Yang Cao; Jue Wang; Mi Zhou; Liting Chen; Jia Wei; Zekai Mao; Di Wang; Yi Xiao; Haichuan Zhu; Shangkun Zhang; Tongcun Zhang; Yicheng Zhang; Jianfeng Zhou; Liang Huang
• Keywords: 0301 basic medicine; Anaplastic large cell lymphoma; Research; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; 3. Good health; 03 medical and health sciences; Chimeric antigen receptor T cell therapy; CD30; Refractory or relapsed lymphoma; Diseases of the blood and blood-forming organs; RC633-647.5; Autologous hematopoietic stem cell transplantation; Hodgkin lymphoma; RC254-282

Abstract Background Long-term outcome is unfavourable for relapsed/refractory (r/r) lymphoma patients who are resistant to salvage chemotherapy, even after subsequent autologous stem-cell transplantation (ASCT). Although anti-CD30 chimeric antigen receptor (CAR30) T-cell therapy induces high response rates in these patients, the duration of response is relatively limited.

Methods This open-label, single-center and single-arm pilot study investigated the safety and efficacy of ASCT in tandem with CAR30 T-cell infusion in r/r CD30+ lymphoma. The primary endpoint was safety and key secondary endpoint was overall response rate, overall survival, progression-free survival, and duration of response.

Results Five classical Hodgkin lymphoma (cHL) patients and 1 anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL) patient were enrolled. The median age was 24 years. No patient had prior ASCT. Three patients (50.0%) relapsed for ≥ 2 times and 3 patients (50.0%) had primary refractory diseases. All had a Deauville score of 4 or 5, and 5 patients (83.3%) had a stable or progressive disease (SD/PD) at enrollment. All patients received myeloablative chemotherapy and infused CD34-positive hematopoietic stem cells (HSCs) and CAR30 T cells in tandem, with a median dose of 3.9 × 106/kg and 7.6 × 106/kg, respectively. Five paitents presented with cytokine release syndrome (CRS), all of which were grade 1. No neurotoxicity was observed. All patients had successful HSCs engraftment and reached an objective response, including 5 (4 cHL and 1 ALCL, 83.3%) with a complete response (CR) and 1 with a partial response (PR). With a median follow-up of 20.4 (range, 12.1–34.4) months, all remained alive and maintained their responses.

Conclusion Our work demonstrates the combined administration of ASCT and CAR30 T-cell therapy is well-tolerate and highly effective in r/r cHL and ALCL, even in PET-positive or chemorefractory patients who are expected to have inferior outcome after ASCT, although further large-scaled validation in prospective clinical trial is warranted. Trial registration The trial was registered with the Chinese Clinical Trial Registry (ChiCTR, number ChiCTR2100053662).