Sequential CD19/22 CAR T-cell immunotherapy following autologous stem cell transplantation for central nervous system lymphoma

Jiaying Wu,Na Wang,Lifang Huang,Yi Xiao,Jue Wang,Jianfeng Zhou,Xiaojian Zhu,Yicheng Zhang,Fankai Meng,Yang Cao

doi:10.1038/s41408-021-00523-2

Abstract

Chimeric antigen receptor (CAR) T-cell immunotherapy following autologous stem cell transplantation (ASCT) is a promising method for refractory or relapsed multiple myeloma, but explicit data for central nervous system lymphoma (CNSL) are lacking. Here, we treated 13 CNSL patients with ASCT sequential CD19/22 CAR T-cell infusion and simultaneously evaluated the clinical efficacy and toxicity. The 13 CNSL patients analyzed included four primary CNSL and nine secondary CNSL patients. Patients 1 and 10, who had complete remission status before enrollment, maintained clinical efficacy without recurrence. Nine of the remaining 11 patients responded to our protocol with a median durable time of 14.03 months, and the overall response and complete remission rate were 81.81% and 54.55%, respectively. No patient suffered grades 3–4 cytokine-release syndrome (CRS), and only patient 10 experienced severe immune effector cell-associated neurotoxicity syndrome (ICANS). In addition, increases in serum ferritin and interleukin-6 levels were often accompanied by CRS and ICANS. After a median follow-up time of 14.20 months, the estimated 1-year progression-free survival and overall survival rates were 74.59% and 82.50%, respectively. Sequential CD19/22 CAR T-cell immunotherapy following ASCT as a novel method for CNSL appears to have encouraging long-term efficacy with relatively manageable side effects.

Highlights

1, Na Wang1, Jue Wang1, Lifang Huang1, Chimeric antigen receptor (CAR) T-cell immunotherapy following autologous stem cell transplantation (ASCT) is a promising method for refractory or relapsed multiple myeloma, but explicit data for central nervous system lymphoma (CNSL) are lacking
Another study conducted by our department showed an objective response in CNSL patients who received CD19/ 22 CAR T-cell infusion, but only one complete remission (CR) case enrolled in another clinical trial of ASCT sequential CD19/22 CAR T-cell infusion achieved long-term progression/relapse-free survival; this finding demonstrated that separate CAR T-cell immunotherapy was effective but not long-lasting for CNSL, and the new model of CAR T-cell immunotherapy following ASCT provided a promising direction and option for the treatment of CNSL [16]
Among the nine Secondary CNSL (SCNSL) patients, two had CNS involvement at the initial diagnosis, three systemic non-Hodgkin lymphoma (NHL) patients were refractory to chemotherapy and experienced CNS involvement in the course of treatment, and the remaining four systemic NHL patients previous with CR status developed CNS recurrence

Summary

Introduction

1, Na Wang1, Jue Wang1, Lifang Huang1, Chimeric antigen receptor (CAR) T-cell immunotherapy following autologous stem cell transplantation (ASCT) is a promising method for refractory or relapsed multiple myeloma, but explicit data for central nervous system lymphoma (CNSL) are lacking. Our results indicate that sequential CD19/22 CAR T-cell immunotherapy following ASCT is a novel and promising method for CNSL patients to achieve long-term remission with manageable side effects.

Results

Conclusion