Successful BCMA CAR-T Therapy for Multiple Myeloma With Central Nervous System Involvement Manifesting as Cauda Equina Syndrome-A Wandering Road to Remission.

Yiyun Wang,Guoqing Wei,Ruimin Hong,Houli Zhao,Linqin Wang,Yifan Zeng,Yongxian Hu,Cheng Zu,Li Yang,Aiyun Jin,He Huang,Elaine Tan Su Yin

doi:10.3389/fonc.2021.755584

Abstract

Multiple myeloma (MM) with central nervous system (CNS) involvement is rare with only 1% incidence. So far, there is no standard or effective treatment for CNS MM, and the expected survival time is fewer than 6 months. Here, we report a case of MM with CNS involvement presented with cauda equina syndrome (CES) who achieved complete remission after anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T (CAR-T) cell therapy (Chictr.org.cn, ChiCTR1800017404). The expansion of BCMA CAR-T cells was observed in both peripheral blood (PB) and cerebrospinal fluid (CSF). The CAR-T cells peaked at 2.4 × 106/l in CSF at day 8 and 4.1 × 109/l in PB at day 13. The peak concentration of interleukin (IL)-6 in CSF was detected 3 days earlier, and almost five times higher than that in PB. Next, morphological analysis confirmed the elimination of nucleated cells in CSF 1 month after CAR-T cell treatment from 300 cells/μl, and the patient achieved functional recovery with regressed lesion shown in PET-CT. The case demonstrated that BCMA CAR-T cells are effective and safe in this patient population.

Highlights

Multiple myeloma (MM) is a clonal plasma cell malignancy which accounted for 10% of hematologic malignancies
We report a case of refractory/relapsed MM with central nervous system (CNS) involvement, manifesting as cauda equina syndrome (CES), and demonstrate the safety and effectiveness of B-cell maturation antigen (BCMA) chimeric antigen receptor T (CAR-T) therapy in this patient population
He was enrolled in BCMA CAR-T therapy trial (Chictr.org.cn, ChiCTR1800017404, details regarding the design of this trial are accessible at https://www.chictr.org.cn/showproj.aspx? proj=28864) after the approval by the ethics committee of the First Affiliated Hospital of Zhejiang University

Summary

INTRODUCTION

Multiple myeloma (MM) is a clonal plasma cell malignancy which accounted for 10% of hematologic malignancies. We report a case of refractory/relapsed MM with CNS involvement, manifesting as cauda equina syndrome (CES), and demonstrate the safety and effectiveness of BCMA CAR-T therapy in this patient population. In addition to the scFv, a 4-1BB co-stimulatory domain and a CDz3-signaling domain were inserted into a lentiviral vector as well The blood cells were transduced with BCMA CAR using lentivirus He received a fludarabine- (30 mg/m2, day -4 to -2) and cyclophosphamide- (500 mg/m2, day -3 to -2) based lymphodepletion regimen before CAR-T cell infusion. The expansions of in vivo CAR-T cells in the peripheral blood and CSF were continuously detected by flow cytometry. The methods to assess the treatment response included morphological analysis, flow cytometry, and MRI

METHODS

RESULTS AND DISCUSSION

ETHICS STATEMENT