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Cited by 89CAR-T cell therapy researchMultiple Myeloma Research and TreatmentsImmunotherapy and Immune Responses

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High efficacy and safety of CD38 and BCMA bispecific CAR-T in relapsed or refractory multiple myeloma

Open access
Tang, Yuanyan, Yin, Haisen, Zhao, Xinying, Jin, Dan, Liang, Yan, Xiong, Tao, Li, Lu, Tang, Wen, Zhang, Jiangzhao, Liu, Min, Yu, Zhuojun, Liu, Huimin, Zang, Sibin, Huang, Zhiping·2022·Journal of Experimental & Clinical Cancer Research
DOI 10.1186/s13046-021-02214-zPMC PMC8722124
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Abstract

Background: B-cell maturation antigen (BCMA) chimeric antigen receptor T (CAR-T) cell therapy has obtained promising results in relapsed or refractory multiple myeloma (R/R MM), while some patients do not response, or relapse in short term after treatment. Combining with anti-CD38 might solve the problem of targeting BCMA alone. We aimed to assess the efficacy and safety of BCMA and CD38 (BCMA-CD38) bispecific CAR-T cells in R/R MM patients. Methods: We did a single-center, single-arm clinical study at the Second Affiliated Hospital of Yangtze University in China. Patients meeting with the inclusion criteria were administered with fludarabine and cyclophosphamide before CAR-T cells infusion. Response and adverse events were assessed after infusion. This study was registered with the Chinese Clinical Trial Registration Center (ChiCTR1900026286). Results: First, we found BCMA-CD38 CAR-T cells exhibited enhanced killing effect on BCMA+CD38+ cells in vitro, compared to BCMA CAR-T and CD38 CAR-T cells. We further demonstrated its anti-tumor activity in vivo. Then, we enrolled 16 R/R MM patients for safety and efficacy analyses. Of the 16 evaluable patients, 14 (87.5%) respond to the treatment, including 13 stringent complete response (sCR) and one partial response (PR), while two patients did not respond. At a median follow-up of 11.5 months, of the 13 patients who achieved sCR, 76.9% (10/13) did not relapse or progress during follow-up. Relapse occurred in 3 patients (Patient 2, 3 and 4) after achieving sCR. In sum, four patients died, of which one died of hemophagocytic lymphohistiocytosis syndrome secondary to severe cytokine release syndrome (CRS) and three died of disease progression or relapse. The 1-year progression-free survival rates was 68.8%. The 1-year overall survival rate was 75.0%. Extramedullary lesions were eliminated in 62.5% (5/8) patients. The most common symptoms after CAR-T infusion were cytopenia (16, 100%), fever (10, 62.5%), fatigue (8, 50.0%) and myalgias (8, 50.0%). Twelve patients (75.0%) were observed with various grades of CRS, of which five patients (31.3%) got serious CRS (Grade ≥ 3). The CAR+ cell expansion levels were associated with the severity of CRS. Transient clonal isotype switch was observed after CAR-T infusion. Conclusion: Our results confirm that BCMA-CD38 CAR-T cells therapy is feasible in treating R/R MM patients, with high response rate, low recurrence rate and manageable CRS, which will be a promising treatment option for R/R MM. Trial registration: ChiCTR1900026286, registered on September 29, 2019, retrospectively registered, URL: https://www.chictr.org.cn/showproj.aspx?proj=43805

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  • CAR-T cells targeting GPRC5D, CD19, CD38, CD138, CS1, and NKG2D are under exploration for MM treatment.

    “Several CAR-T cells targeting antigens, such an GPRC5D [229–231], CD19 [232, 233], CD38 [234–236], CD138 [237], CS1 [238–240] and NKG2D [241, 242] are also under exploration for their efficacy in MM treatment.”

    From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [235]

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Metadata

Authors
Tang, Y., Yin, H., Zhao, X., Jin, D., Liang, Y., Xiong, T., Li, L., Tang, W., Zhang, J., Liu, M., Yu, Z., Liu, H., Zang, S., & Huang, Z.
Affiliations
  • Renmin Hospital of Wuhan University (CN)
  • Yangtze University (CN)
Corresponding author
Huang, Zhiping
ORCID
Venue
Journal of Experimental & Clinical Cancer Research
Publisher
Springer Science and Business Media LLC
Published
2022-01-03
Volume
41
Issue
1
Pages
2-2
ISSN
  • 0392-9078 (ISSN-L)
  • 1756-9966
DOI
10.1186/s13046-021-02214-z
PMC
PMC8722124
OpenAlex
W4206835598
Cited by
89
References
1
Citations by year
2026: 11 · 2025: 23 · 2024: 28 · 2023: 18 · 2022: 9
FWCI
8.89
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Experimental & Clinical Cancer Research (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Health Commission of Hubei Province
Topics
  • Health Sciences › Medicine › Oncology › CAR-T cell therapy research
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
relapsed/refractory multiple myeloma, BCMA, CD38, bispecific CAR T cells, CAR T-cell therapy, cytokine release syndrome, hemophagocytic lymphohistiocytosis, progression-free survival, overall survival, extramedullary lesions, CAR T cell manufacturing, fludarabine and cyclophosphamide
MeSH terms
Receptors, Chimeric Antigen, Humans, Male, Multiple Myeloma, Survival Analysis, ADP-ribosyl Cyclase 1, B-Cell Maturation Antigen

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