Anti–G Protein–Coupled Receptor, Class C Group 5 Member D Chimeric Antigen Receptor T Cells in Patients With Relapsed or Refractory Multiple Myeloma: A Single-Arm, Phase Ⅱ Trial
Open accessAbstract
PURPOSE: G protein–coupled receptor, class C group 5 member D (GPRC5D) is considered to be a promising surface target for multiple myeloma (MM) immunotherapy. Here, we report the efficacy and safety of anti-GPRC5D chimeric antigen receptor (CAR) T cells in patients with relapsed or refractory (R/R) MM. METHODS: This phase Ⅱ, single-arm study enrolled patients (18-70 years) with R/R MM. Lymphodepletion was performed before patients received 2 × 10 6/kg anti-GPRC5D CAR T cells. The primary end point was the proportion of patients who achieved an overall response. Safety was also evaluated in eligible patients. RESULTS: From September 1, 2021, to March 23, 2022, 33 patients were infused with anti-GPRC5D CAR T cells. At a median follow-up of 5.2 months (range, 3.2‐8.9), the overall response rate was 91% (95% CI, 76 to 98; 30 of 33 patients), including 11 (33%) stringent complete responses, 10 (30%) complete responses, four (12%) very good partial responses, and five (15%) partial responses. Partial responses or better were observed in nine (100%) of nine patients with previous anti–B-cell maturation antigen (BCMA) CAR T-cell therapy, including two patients who had received repeated anti-BCMA CAR T-cell infusions with no responses at the last time. Grade 3 or higher hematologic toxicities were neutropenia (33 [100%]), anemia (17 [52%]), and thrombocytopenia (15 [45%]). Cytokine release syndrome occurred in 25 (76%) of 33 patients (all were grade 1 or 2), and neurotoxicities in three patients (one grade 2 and one grade 3 ICANSs and one grade 3 headache). CONCLUSION: Anti-GPRC5D CAR T-cell therapy showed an encouraging clinical efficacy and manageable safety profile in patients with R/R MM. For patients with MM that progressed after anti-BCMA CAR T-cell therapy or that is refractory to anti-BCMA CAR T cell, anti-GPRC5D CAR T-cell therapy might be a potential alternative option.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
79% (26/33) achieved bone marrow MRD negativity.
“Results showed that the median follow-up was 5.2 months, the ORR was 91% (30/33), 33% (11/33) sCR, 30% (10/33) CR, 12% (4/33) VGPR, 15% (5/33) PR, and 79% (26/33) achieved bone marrow MRD negativity.”
From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [257]
In the phase II single-arm study of anti-GPRC5D CAR-T (ChiCTR2100048888), the ORR was 91% (30/33), with 33% (11/33) sCR, 30% (10/33) CR, 12% (4/33) VGPR, and 15% (5/33) PR.
“Results showed that the median follow-up was 5.2 months, the ORR was 91% (30/33), 33% (11/33) sCR, 30% (10/33) CR, 12% (4/33) VGPR, 15% (5/33) PR, and 79% (26/33) achieved bone marrow MRD negativity.”
From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [257]
The therapy showed efficacy even in patients who had progressed after anti-BCMA CAR-T cell therapy, with 100% (9/9) of these patients having partial responses or better.
“The therapy showed efficacy even in patients who had progressed after anti-BCMA CAR-T cell therapy, with 100% (9/9) of these patients having partial responses or better.”
From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [257]
CRS occurred in 76% (25/33) of patients, with all events being grade 1 or 2.
“CRS occurred in 76% (25/33) of patients, with all events being grade 1 or 2, indicating manageable toxicity [257].”
From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [257]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma.
Munshi, N. C., Anderson, L. D., Shah, N., Madduri, D., Berdeja, J., Lonial, S., Raje, N., Lin, Y., Siegel, D., Oriol, A., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2024850 · Cited by 2,560 · see citing works
Berdeja, J. G., Madduri, D., Usmani, S. Z., Jakubowiak, A., Agha, M., Cohen, A. D., Stewart, A. K., Hari, P., Htut, M., Lesokhin, A., et al. (2021) · The Lancet · doi:10.1016/s0140-6736(21)00933-8 · Cited by 1,756 · see citing works
GPRC5D is a target for the immunotherapy of multiple myeloma with rationally designed CAR T cells
Smith, E. L., Harrington, K., Staehr, M., Masakayan, R., Jones, J., Long, T. J., Ng, K. Y., Ghoddusi, M., Purdon, T. J., Wang, X., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aau7746 · Cited by 391 · see citing works
Self-citationAnti-GPRC5D/CD3 Bispecific T-Cell–Redirecting Antibody for the Treatment of Multiple Myeloma
Kodama, T., Kochi, Y., Nakai, W., Mizuno, H., Baba, T., Habu, K., Sawada, N., Tsunoda, H., Shima, T., Miyawaki, K., et al. (2019) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-18-1216 · Cited by 80 · see citing works
Flagged first, then by citations
Research works printed but not linked: 22
- [1]Carpenter RO Evbuomwan MO Pittaluga S: B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma. Clin Cancer Res 19: 2048- 2060, 2013 23344265 PMC3630268
- [2]Ali SA Shi V Maric I: T cells expressing an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma. Blood 128: 1688- 1700, 2016 27412889 PMC5043125
- [3]Novak AJ Darce JR Arendt BK: Expression of BCMA, TACI, and BAFF-R in multiple myeloma: A mechanism for growth and survival. Blood 103: 689- 694, 2004 14512299
- [4]Madry C Laabi Y Callebaut I: The characterization of murine BCMA gene defines it as a new member of the tumor necrosis factor receptor superfamily. Int Immunol 10: 1693- 1702, 1998 9846698
- [5]Sanchez E Li M Kitto A: Serum B-cell maturation antigen is elevated in multiple myeloma and correlates with disease status and survival. Br J Haematol 158: 727- 738, 2012 22804669
- [6]Brudno JN Maric I Hartman SD: T cells genetically modified to express an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of poor-prognosis relapsed multiple myeloma. J Clin Oncol 36: 2267- 2280, 2018 29812997 PMC6067798
- [7]Raje N Berdeja J Lin Y: Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma. N Engl J Med 380: 1726- 1737, 2019 31042825 PMC8202968
- [9]Yan Z Cao J Cheng H: A combination of humanised anti-CD19 and anti-BCMA CAR T cells in patients with relapsed or refractory multiple myeloma: A single-arm, phase 2 trial. Lancet Haematol 6: e521- e529, 2019 31378662
- [10]Cohen AD Garfall AL Stadtmauer EA: B cell maturation antigen-specific CAR T cells are clinically active in multiple myeloma. J Clin Invest 129: 2210- 2221, 2019 30896447 PMC6546468
- [13]Atamaniuk J Gleiss A Porpaczy E: Overexpression of G protein-coupled receptor 5D in the bone marrow is associated with poor prognosis in patients with multiple myeloma. Eur J Clin Invest 42: 953- 960, 2012 22591013
- [15]Rajkumar SV Dimopoulos MA Palumbo A: International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 15: e538- e548, 2014 25439696
- [16]Palumbo A Rajkumar SV San Miguel JF: International Myeloma Working Group consensus statement for the management, treatment, and supportive care of patients with myeloma not eligible for standard autologous stem-cell transplantation. J Clin Oncol 32: 587- 600, 2014 24419113 PMC3918540
- [18]Lee DW Santomasso BD Locke FL: ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant 25: 625- 638, 2019 30592986 PMC12180426
- [19]van Dongen JJM Lhermitte L Bottcher S: EuroFlow antibody panels for standardized n-dimensional flow cytometric immunophenotyping of normal, reactive and malignant leukocytes. Leukemia 26: 1908- 1975, 2012 22552007 PMC3437410
- [20]Mailankody S Devlin SM Landa J: GPRC5D-targeted CAR T cells for myeloma. N Engl J Med 387: 1196- 1206, 2022 36170501 PMC10309537
- [21]Roex G Timmers M Wouters K: Safety and clinical efficacy of BCMA CAR-T-cell therapy in multiple myeloma. J Hematol Oncol 13: 164, 2020 33272302 PMC7713173
- [22]Laurent SA Hoffmann FS Kuhn PH: γ-Secretase directly sheds the survival receptor BCMA from plasma cells. Nat Commun 6: 7333, 2015 26065893 PMC4490565
- [25]Fernández de Larrea C Staehr M Lopez AV: Defining an optimal dual-targeted CAR T-cell therapy approach simultaneously targeting BCMA and GPRC5D to prevent BCMA escape-driven relapse in multiple myeloma. Blood Cancer Discov 1: 146- 154, 2020 33089218 PMC7575057
- [26]Inoue S Nambu T Shimomura T: The RAIG family member, GPRC5D, is associated with hard-keratinized structures. J Invest Dermatol 122: 565- 573, 2004 15086536
- [27]Bräuner-Osborne H Jensen AA Sheppard PO: Cloning and characterization of a human orphan family C G-protein coupled receptor GPRC5D. Biochim Biophys Acta (BBA) 1518: 237- 248, 2001 11311935
- [28]Wang Y Cao J Gu W: Long-term follow-up of combination of B-cell maturation antigen and CD19 chimeric antigen receptor T cells in multiple myeloma. J Clin Oncol 40: 2246- 2256, 2022 35333600
- [29]Wang Y Li C Xia J: Humoral immune reconstitution after anti-BCMA CAR T-cell therapy in relapsed/refractory multiple myeloma. Blood Adv 5: 5290- 5299, 2021 34587230 PMC9153033
Cited by
Sorted by citations
Multiple myeloma: signaling pathways and targeted therapy
Lu, Q., Yang, D., Li, H., Niu, T., & Tong, A. (2024) · Molecular biomedicine · doi:10.1186/s43556-024-00188-w · Cited by 90 · see citing works
Self-citation
- Authors
- Xia, J., Li, H., Yan, Z., Zhou, D., Wang, Y., Qi, Y., Cao, J., Li, D., Cheng, H., Sang, W., Zhu, F., Sun, H., Chen, W., Qi, K., Yan, D., Qiu, T., Qiao, J., Yao, R., Liu, Y., Wang, X., Zhang, Y., Peng, S., Huang, C.-H., Zheng, J., Li, Z., Chang, A. H., & Xu, K.
- Affiliations
- Xuzhou Medical College (CN)
- Shanghai YaKe Biotechnology Ltd, Shanghai, China
- Tongji University (CN)
- Corresponding author
- Xu, Kailin
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2023-05-10
- Volume
- 41
- Issue
- 14
- Pages
- 2583-2593
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- PMC
- PMC10414745
- OpenAlex
- W4323351721
- Cited by
- 94
- References
- 4
- Citations by year
- 2026: 12 · 2025: 32 · 2024: 33 · 2023: 15 · 2013: 1
- FWCI
- 11.22
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Journal of Clinical Oncology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81930005, 81871263)
- 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
- GPRC5D, chimeric antigen receptor T cells, multiple myeloma, relapsed/refractory multiple myeloma, CAR T-cell therapy, overall response rate, cytokine release syndrome, neurotoxicity, hematologic toxicity, immunotherapy
- MeSH terms
- Receptors, Chimeric Antigen, Adolescent, Adult, Aged, Anemia, Antibodies, Humans, Middle Aged, Multiple Myeloma, T-Lymphocytes, Immunotherapy, Adoptive, Treatment Outcome, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
