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Case Reports
. 2018 Oct 22;11(1):128.
doi: 10.1186/s13045-018-0672-7.

Anti-BCMA CAR-T cells for treatment of plasma cell dyscrasia: case report on POEMS syndrome and multiple myeloma

Jinhuan Xu  1   2 , Qiuxiang Wang  1   2 , Hao Xu  1   2 , Chaojiang Gu  3 , Lijun Jiang  1   2 , Jue Wang  1   2 , Di Wang  1   2 , Bin Xu  1   2 , Xia Mao  1   2 , Jin Wang  1   2 , Zhiqiong Wang  1   2 , Yi Xiao  1   2 , Yicheng Zhang  1   2 , Chunrui Li  4   5 , Jianfeng Zhou  6   7
Affiliations
Case Reports

Anti-BCMA CAR-T cells for treatment of plasma cell dyscrasia: case report on POEMS syndrome and multiple myeloma

Jinhuan Xu et al. J Hematol Oncol. .

Abstract

Background: POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome still has no standard treatment. On the basis that both POEMS syndrome and myeloma have an underlying plasma cell dyscrasia, anti-myeloma therapy can be expected to be useful for POEMS syndrome. Chimeric antigen receptor T (CAR-T) cells targeting B cell maturation antigen (BCMA) has been used in the treatment of relapsed and refractory multiple myeloma (RRMM). No POEMS syndrome cases treated with anti-BCMA CAR-T cells have been reported.

Case presentation: Here, we, for the first time, report a POEMS syndrome case treated with anti-BCMA CAR-T cells. A 49-year-old female with incapacitating POEMS syndrome that progressed on lenalidomide treatment was enrolled in a phase I study involving anti-BCMA CAR-T cells (ChiCTR-OPC-16009113). Another patient with RRMM who had undergone six prior lines treatments was also enrolled in the study. They received infusions of anti-BCMA CAR-T cells. Both patients achieved a stringent complete response. Complete remission persisted in the patient with POEMS syndrome and lasted for 7.6 months before a relapse in RRMM patient. Both patients had toxicity consistent with the grade 1 cytokine release syndrome.

Conclusions: This is the first report of treatment by anti-BCMA CAR-T cells in POEMS syndrome. Our findings demonstrate the anti-BCMA CAR-T cell treatment may be a feasible therapeutic option for patients with POEMS syndrome and RRMM who do not respond well to traditional therapies.

Trial registration: ChiCTR-OPC, ChiCTR-OPC-16009113 . Registered 29 August 2016.

Keywords: B cell maturation antigen; Chimeric antigen receptor T cells; Multiple myeloma; POEMS syndrome; Remissions.

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Conflict of interest statement

Ethics approval and consent to participate

This study was approved by the Medical Ethics Committee of the Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (TJ-IRB20160315). The patient and donor gave their written informed consent in accordance with the Declaration of Helsinki. This study is registered at http://www.chictr.org.cn as ChiCTR-OPC-16009113.

Consent for publication

The authors have obtained consent to publish from the participants to report individual patient data.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Bone marrow core biopsy and cell samples obtained before and after anti-BCMA CAR-T cells infusion a Hematoxylin and eosin staining, Immunohistochemical (IHC) staining for CD138 and BCMA. Bone marrow cells were 3% plasma cells as shown by CD138 staining at 7 days before the anti-BCMA CAR-T cells infusion. BCMA expression was uniform on the CD138 positive plasma cells (original magnification, × 400). b No plasma cells on hematoxylin and eosin staining, CD138, and BCMA immunostaining on day 60 after anti-BCMA CAR-T cells infusion (original magnification, × 400). c Flow cytometry showed uniform BCMA expression on CD38-positive malignant plasma cells before the anti-BCMA CAR-T cells infusion. d No plasma cells in the bone marrow cells on day 60 after anti-BCMA CAR-T cells infusion
Fig. 2
Fig. 2
Measures of POEMS syndrome burden and clinical responses to infusions of anti-BCMA CAR-T cells. a The trend in IgG and M spike concentrations on the course of the all treatment, with PDN combined HGG, with LEN combined DXM and anti-BCMA CAR-T cells infusion. b Serum soluble BCMA and VEGF of the patients was measured by ELISA before, and after anti-BCMA CAR-T cells infusion, they both decreased post-treatment obviously. c Twenty-four hours after anti-BCMA CAR-T cells infusion, the patient became febrile. She was febrile for 7 days. The plot shows the maximum temperature for each day. Serum levels of cytokines were measured at the indicated time points. Levels of IL-6 and ferritin elevated markedly on day 3 and then dropped quickly. d Changes in the white blood cell and platelet count, hemoglobin level. e Anti-BCMA CAR-T cells engraftment, measured by means of flow cytometry as the number of cells per cubic millimeter, and the corresponding B cell frequencies, measured as the number of cells per cubic millimeter (in peripheral blood)
Fig. 3
Fig. 3
Construction of BCMA-specific CAR and protocol of anti-BCMA CAR-T cell infusions following chemotherapy. a Schematic diagram of anti-BCMA CAR vector. SP signal peptide, VH variable H chain, L linker, VL variable L chain. A protocol of CAR-T infusion in combination with chemotherapy. Chemotherapy included fludarabine and cyclophosphamide. CAR-T cells were infused at a total dose of 1 × 107/kg for 3 days (b a patient of POEMS syndrome) and 5.6 × 106/kg for 2 days (c a patient of multiple myeloma)
Fig. 4
Fig. 4
Measures of multiple myeloma burden and clinical responses to infusions of anti-BCMA CAR-T cells. a Before protocol treatment, the patient had a hypercellular bone marrow (hematoxylin and eosin). Bone marrow cells were 25% plasma cells as shown by CD138 staining. BCMA expression was obvious (original magnification, × 400). b Three months after CAR-T cell infusion, bone marrow plasma cells were completely absent as shown by the negative CD138 and BCMA staining (original magnification, × 400). c The trend in the patient’s serum M spike, free light chains, and BCMA concentrations after anti-BCMA CAR-T cells infusion, all of which decreased obviously. In the eighth month, these indicators began to rise. d Anti-BCMA CAR-T cells engraftment, measured by means of flow cytometry as the number of cells per cubic millimeter, and the corresponding B cell frequencies, measured as the number of cells per cubic millimeter (in peripheral blood). e 72 h after CAR-BCMA infusion, the patient became febrile. She was febrile for 7 days. The plot shows the maximum temperature for each day. The levels of IL-6 and ferritin was elevated
See this image and copyright information in PMC

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