单位:[1]Huazhong Univ Sci & Technol,Tongji Hosp,Tongji Med Coll,Dept Hematol,1095 Jiefang Ave,Wuhan 430030,Hubei,Peoples R China[2]Immunothera Py Res Ctr Hematol Dis Hubei Prov,Wuhan 430030,Hubei,Peoples R China[3]Wuhan Univ Sci & Technol,Coll Life Sci & Hlth,Wuhan 430065,Hubei,Peoples R China[4]Wuhan Bioraid Biotechnol CO LTD,Wuhan 430078,Hubei,Peoples R China
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 x 10(6)/kg and 7.6 x 10(6)/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).
基金:
Key Program of the National Natural Science Foundation of China [81830008]; National Natural Science Foundation of China [82070211, 81670152]; National High Technology Research and Development Program of China (863 program) [2014AA020532]; Milstein Medical Asian American Partnership Foundation (2018 MMAAP Foundation Hematology Fellowship Award); Young Top-notch Talent Cultivation Program of Hubei Province
第一作者单位:[1]Huazhong Univ Sci & Technol,Tongji Hosp,Tongji Med Coll,Dept Hematol,1095 Jiefang Ave,Wuhan 430030,Hubei,Peoples R China[2]Immunothera Py Res Ctr Hematol Dis Hubei Prov,Wuhan 430030,Hubei,Peoples R China
通讯机构:[1]Huazhong Univ Sci & Technol,Tongji Hosp,Tongji Med Coll,Dept Hematol,1095 Jiefang Ave,Wuhan 430030,Hubei,Peoples R China[*1]Huazhong Univ Sci & Technol,Tongji Hosp,Tongji Med Coll,Dept Hematol,1095 Jiefang Ave,Wuhan 430030,Hubei,Peoples R China[2]Immunothera Py Res Ctr Hematol Dis Hubei Prov,Wuhan 430030,Hubei,Peoples R China[*2]Immunothera Py Res Ctr Hematol Dis Hubei Prov,Wuhan 430030,Hubei,Peoples R China
推荐引用方式(GB/T 7714):
Zhang Peiling,Yang Xiuxiu,Cao Yang,et al.Autologous stem cell transplantation in tandem with Anti-CD30 CAR T-cell infusion in relapsed/refractory CD30(+) lymphoma[J].EXPERIMENTAL HEMATOLOGY & ONCOLOGY.2022,11(1):72.doi:10.1186/s40164-022-00323-9.
APA:
Zhang, Peiling,Yang, Xiuxiu,Cao, Yang,Wang, Jue,Zhou, Mi...&Huang, Liang.(2022).Autologous stem cell transplantation in tandem with Anti-CD30 CAR T-cell infusion in relapsed/refractory CD30(+) lymphoma.EXPERIMENTAL HEMATOLOGY & ONCOLOGY,11,(1)
MLA:
Zhang, Peiling,et al."Autologous stem cell transplantation in tandem with Anti-CD30 CAR T-cell infusion in relapsed/refractory CD30(+) lymphoma".EXPERIMENTAL HEMATOLOGY & ONCOLOGY 11..1(2022)