Five-year remission without disease progression in a patient with relapsed/refractory multiple myeloma with extramedullary disease treated with LCAR-B38M chimeric antigen receptor T cells in the LEGEND-2 study: a case report
Abstract Background Multiple myeloma remains incurable despite treatment advancements over the last 20 years. LCAR-B38M Cells in Treating Relapsed/Refractory Multiple Myeloma was a phase 1, first-in-human, investigator-initiated study in relapsed/refractory multiple myeloma conducted at four sites i...
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | Journal of Medical Case Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13256-022-03636-9 |
| _version_ | 1828278227793084416 |
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| author | Bai-Yan Wang Wan-Hong Zhao Yin-Xia Chen Xing-Mei Cao Yun Yang Yi-Lin Zhang Fang-Xia Wang Peng-Yu Zhang Bo Lei Liu-Fang Gu Jian-Li Wang Ju Bai Yan Xu Xu-Geng Wang Rui-Li Zhang Li-Li Wei Qiu-Chuan Zhuang Frank Fan Wang-Gang Zhang Ai-Li He Jie Liu |
| author_facet | Bai-Yan Wang Wan-Hong Zhao Yin-Xia Chen Xing-Mei Cao Yun Yang Yi-Lin Zhang Fang-Xia Wang Peng-Yu Zhang Bo Lei Liu-Fang Gu Jian-Li Wang Ju Bai Yan Xu Xu-Geng Wang Rui-Li Zhang Li-Li Wei Qiu-Chuan Zhuang Frank Fan Wang-Gang Zhang Ai-Li He Jie Liu |
| author_sort | Bai-Yan Wang |
| collection | DOAJ |
| description | Abstract Background Multiple myeloma remains incurable despite treatment advancements over the last 20 years. LCAR-B38M Cells in Treating Relapsed/Refractory Multiple Myeloma was a phase 1, first-in-human, investigator-initiated study in relapsed/refractory multiple myeloma conducted at four sites in China. The study used LCAR-B38M chimeric antigen receptor-T cells expressing two B-cell maturation antigen-targeting single-domain antibodies designed to confer avidity, and a CD3ζ signaling domain with a 4-1BB costimulatory domain to optimize T-cell activation and proliferation. This chimeric antigen receptor construct is identical to ciltacabtagene autoleucel. In the LEGEND-2 study (n = 57, Xi’an site), overall response rate was 88%; median (95% CI) progression-free survival and overall survival were 19.9 (9.6–31.0) and 36.1 (26.4–not evaluable) months, respectively; and median follow-up was 25 months. This case study reports on a patient with relapsed/refractory multiple myeloma (λ light chain type) who was treated with LCAR-B38M chimeric antigen receptor T cells in the LEGEND-2 study (Xi’an site); he had received five prior lines of treatment and had extensive extramedullary lesions. Case presentation The patient, a 56-year-old Asian male, received cyclophosphamide (500 mg daily × 3 days) as lymphodepletion therapy and a total dose of 0.5 × 106 chimeric antigen receptor + T cells/kg split into three infusions (days 1, 24, and 84 from June to August 2016). He experienced grade 2 cytokine release syndrome after the first infusion; all symptoms resolved with treatment. No cytokine release syndrome occurred following the second and third infusions. His λ light chain levels decreased and normalized 20 days after the first infusion, and extramedullary lesions were healed as of January 2018. He has sustained remission for 5 years and received no other multiple myeloma treatments after LCAR-B38M chimeric antigen receptor T cell infusion. As of 30 October 2020, the patient is still progression-free and has maintained minimal residual disease-negative (10–4) complete response status for 52 months. Conclusions This case provides support that treatment with LCAR-B38M chimeric antigen receptor T cells can result in long-term disease remission of 5 or more years without disease progression in a heavily pretreated patient with extensive extramedullary disease and no other treatment options. |
| first_indexed | 2024-04-13T07:27:22Z |
| format | Article |
| id | doaj.art-c9b293fef2f645698bfc3549329d7fc0 |
| institution | Directory Open Access Journal |
| issn | 1752-1947 |
| language | English |
| last_indexed | 2024-04-13T07:27:22Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Medical Case Reports |
| spelling | doaj.art-c9b293fef2f645698bfc3549329d7fc02022-12-22T02:56:27ZengBMCJournal of Medical Case Reports1752-19472022-12-011611810.1186/s13256-022-03636-9Five-year remission without disease progression in a patient with relapsed/refractory multiple myeloma with extramedullary disease treated with LCAR-B38M chimeric antigen receptor T cells in the LEGEND-2 study: a case reportBai-Yan Wang0Wan-Hong Zhao1Yin-Xia Chen2Xing-Mei Cao3Yun Yang4Yi-Lin Zhang5Fang-Xia Wang6Peng-Yu Zhang7Bo Lei8Liu-Fang Gu9Jian-Li Wang10Ju Bai11Yan Xu12Xu-Geng Wang13Rui-Li Zhang14Li-Li Wei15Qiu-Chuan Zhuang16Frank Fan17Wang-Gang Zhang18Ai-Li He19Jie Liu20Department of Hematology, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Hematology, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Hematology, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Hematology, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Hematology, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Hematology, The Second Affiliated Hospital of Xi’an Jiaotong UniversityThe Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Hematology, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Hematology, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Hematology, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Hematology, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Hematology, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Hematology, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Hematology, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Hematology, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Hematology, The Second Affiliated Hospital of Xi’an Jiaotong UniversityNanjing Legend BiotechNanjing Legend BiotechDepartment of Hematology, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Hematology and National-Local Joint Engineering Research Center of Biodiagnostics & Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Hematology, The Second Affiliated Hospital of Xi’an Jiaotong UniversityAbstract Background Multiple myeloma remains incurable despite treatment advancements over the last 20 years. LCAR-B38M Cells in Treating Relapsed/Refractory Multiple Myeloma was a phase 1, first-in-human, investigator-initiated study in relapsed/refractory multiple myeloma conducted at four sites in China. The study used LCAR-B38M chimeric antigen receptor-T cells expressing two B-cell maturation antigen-targeting single-domain antibodies designed to confer avidity, and a CD3ζ signaling domain with a 4-1BB costimulatory domain to optimize T-cell activation and proliferation. This chimeric antigen receptor construct is identical to ciltacabtagene autoleucel. In the LEGEND-2 study (n = 57, Xi’an site), overall response rate was 88%; median (95% CI) progression-free survival and overall survival were 19.9 (9.6–31.0) and 36.1 (26.4–not evaluable) months, respectively; and median follow-up was 25 months. This case study reports on a patient with relapsed/refractory multiple myeloma (λ light chain type) who was treated with LCAR-B38M chimeric antigen receptor T cells in the LEGEND-2 study (Xi’an site); he had received five prior lines of treatment and had extensive extramedullary lesions. Case presentation The patient, a 56-year-old Asian male, received cyclophosphamide (500 mg daily × 3 days) as lymphodepletion therapy and a total dose of 0.5 × 106 chimeric antigen receptor + T cells/kg split into three infusions (days 1, 24, and 84 from June to August 2016). He experienced grade 2 cytokine release syndrome after the first infusion; all symptoms resolved with treatment. No cytokine release syndrome occurred following the second and third infusions. His λ light chain levels decreased and normalized 20 days after the first infusion, and extramedullary lesions were healed as of January 2018. He has sustained remission for 5 years and received no other multiple myeloma treatments after LCAR-B38M chimeric antigen receptor T cell infusion. As of 30 October 2020, the patient is still progression-free and has maintained minimal residual disease-negative (10–4) complete response status for 52 months. Conclusions This case provides support that treatment with LCAR-B38M chimeric antigen receptor T cells can result in long-term disease remission of 5 or more years without disease progression in a heavily pretreated patient with extensive extramedullary disease and no other treatment options.https://doi.org/10.1186/s13256-022-03636-9Multiple myelomaCAR-TBCMACase studyExtramedullary disease |
| spellingShingle | Bai-Yan Wang Wan-Hong Zhao Yin-Xia Chen Xing-Mei Cao Yun Yang Yi-Lin Zhang Fang-Xia Wang Peng-Yu Zhang Bo Lei Liu-Fang Gu Jian-Li Wang Ju Bai Yan Xu Xu-Geng Wang Rui-Li Zhang Li-Li Wei Qiu-Chuan Zhuang Frank Fan Wang-Gang Zhang Ai-Li He Jie Liu Five-year remission without disease progression in a patient with relapsed/refractory multiple myeloma with extramedullary disease treated with LCAR-B38M chimeric antigen receptor T cells in the LEGEND-2 study: a case report Journal of Medical Case Reports Multiple myeloma CAR-T BCMA Case study Extramedullary disease |
| title | Five-year remission without disease progression in a patient with relapsed/refractory multiple myeloma with extramedullary disease treated with LCAR-B38M chimeric antigen receptor T cells in the LEGEND-2 study: a case report |
| title_full | Five-year remission without disease progression in a patient with relapsed/refractory multiple myeloma with extramedullary disease treated with LCAR-B38M chimeric antigen receptor T cells in the LEGEND-2 study: a case report |
| title_fullStr | Five-year remission without disease progression in a patient with relapsed/refractory multiple myeloma with extramedullary disease treated with LCAR-B38M chimeric antigen receptor T cells in the LEGEND-2 study: a case report |
| title_full_unstemmed | Five-year remission without disease progression in a patient with relapsed/refractory multiple myeloma with extramedullary disease treated with LCAR-B38M chimeric antigen receptor T cells in the LEGEND-2 study: a case report |
| title_short | Five-year remission without disease progression in a patient with relapsed/refractory multiple myeloma with extramedullary disease treated with LCAR-B38M chimeric antigen receptor T cells in the LEGEND-2 study: a case report |
| title_sort | five year remission without disease progression in a patient with relapsed refractory multiple myeloma with extramedullary disease treated with lcar b38m chimeric antigen receptor t cells in the legend 2 study a case report |
| topic | Multiple myeloma CAR-T BCMA Case study Extramedullary disease |
| url | https://doi.org/10.1186/s13256-022-03636-9 |
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