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

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

doi:10.1186/s40164-022-00323-9

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

Exp Hematol Oncol. 2022 Oct 17;11(1):72. doi: 10.1186/s40164-022-00323-9.

Authors

Peiling Zhang^#^{1

2}, Xiuxiu Yang^#^{1

2}, Yang Cao^#^{1

2}, Jue Wang^{1

2}, Mi Zhou^{1

2}, Liting Chen^{1

2}, Jia Wei^{1

2}, Zekai Mao^{1

2}, Di Wang^{1

2}, Yi Xiao^{1

2}, Haichuan Zhu^{3

4}, Shangkun Zhang^{3

4}, Tongcun Zhang^{3

4}, Yicheng Zhang^{5

6}, Jianfeng Zhou^{7

8}, Liang Huang^{9

10}

Affiliations

¹ Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China.
² Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, 430030, Hubei, China.
³ College of Life Science and Health, Wuhan University of Science and Technology, Wuhan, 430065, Hubei, China.
⁴ Wuhan Bio-Raid Biotechnology CO., LTD, Wuhan, 430078, Hubei, China.
⁵ Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China. yczhang@tjh.tjmu.edu.cn.
⁶ Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, 430030, Hubei, China. yczhang@tjh.tjmu.edu.cn.
⁷ Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China. jfzhou@tjh.tjmu.edu.cn.
⁸ Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, 430030, Hubei, China. jfzhou@tjh.tjmu.edu.cn.
⁹ Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China. lhuang@tjh.tjmu.edu.cn.
¹⁰ Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, 430030, Hubei, China. lhuang@tjh.tjmu.edu.cn.

^# Contributed equally.

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).

Keywords: Anaplastic large cell lymphoma; Autologous hematopoietic stem cell transplantation; CD30; Chimeric antigen receptor T cell therapy; Hodgkin lymphoma; Refractory or relapsed lymphoma.

Abstract

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