Clinical Outcomes of BCMA CAR-T Cells in a Multiple Myeloma Patient With Central Nervous System Invasion

Abstract

Background: Multiple myeloma (MM) is the second most common hematological malignancy that still lacks effective clinical treatments. In particular, MM with central nervous system (CNS) invasion occurs rarely. Although B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor-T (CAR-T) cell therapy has shown great promise for the treatment of relapsed/refractory MM, few studies have reported whether BCMA CAR-T could inhibit MM with CNS invasion.

Case presentation: In this study, we report a special case of a 63-year-old male patient who suffered MM with CNS invasion and presented rapid extramedullary disease (EMD) progression into multiple organs. Before CAR-T cell infusion, this patient received five cycles of bortezomib, Adriamycin, and dexamethasone (PAD) and an autologous transplant as the front-line treatment, followed by two cycles of bortezomib, lenalidomide, and dexamethasone (VRD) as the second-line regimen, and daratumumab, bortezomib, dexamethasone (DVD) as the third-line regimen. Since the patient still showed rapid progressive disease (PD), BCMA CAR-T cells were infused, and 1 month later, a stringent complete response (sCR) was achieved, and the response lasted for 4 months. Meanwhile, only grade 1 cytokine release syndrome (CRS) was observed.

Conclusion: This case report demonstrated that BCMA CAR-T could effectively eradicate CNS-involved MM with low adverse events, suggesting that CAR-T cell therapy could be a feasible therapeutic option for this kind of refractory disease.

Clinical trial registration: https://ClinicalTrials.gov, identifier: NCT04537442.a.

Keywords: BCMA; CAR-T; case report; central nervous system; multiple myeloma.

Conflict of interest statement

TH, YD, YS, FQ, FW, and XL are employed by the Immunochina Pharmaceuticals Co. Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Wang, He, Ma, Yang, Feng, Ding, Shan, Bu, Qi, Wu, Lu and Liu.

Figures

Figure 1

Schematic illustration of the CAR construct and treatment timeline. (A) Composition of CAR molecule. (B) Clinical study design.

Figure 2

Evaluation of CAR ratio, the number of CAR-T cells and cytokines in the peripheral blood. (A) The ratio of BCMA CAR-T cells in total lymphocytes (CAR%) and the absolute number of BCMA CAR-T cells (CAR#) in the peripheral blood of the patient were detected using flow cytometry at the indicated days after CAR-T infusion. (B) The expression levels of cytokines (IL-6, IL-10, and IFN-γ) in the peripheral blood were evaluated using cytometric bead array after CAR-T infusion at the indicated time points.

Figure 3

The concentrations of IgA and M spike before and after BCMA CAR-T cell infusion.

Figure 4

Improvement of abnormal signals in right parietal lobe region (sagittal plane and transverse plane) before and after CAR-T infusion.