BCMA CAR-T therapy combined with pomalidomide is a safe and effective treatment for relapsed/refractory multiple myeloma
Abstract Background B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor T-cell (CAR T-cell) therapy has exhibited remarkable efficacy in refractory or relapsed multiple myeloma (R/R MM), but recurrence and rapid progression of disease are still observed within a short time after trea...
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BMC
2024-11-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-024-05772-w |
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| author | Yuhan Yan Yixuan Tu Qian Cheng Jian Zhang Erhua Wang Zuqun Deng Yan Yu Liwen Wang Rui Liu Ling Chu Liqing Kang Jing Liu Xin Li |
| author_facet | Yuhan Yan Yixuan Tu Qian Cheng Jian Zhang Erhua Wang Zuqun Deng Yan Yu Liwen Wang Rui Liu Ling Chu Liqing Kang Jing Liu Xin Li |
| author_sort | Yuhan Yan |
| collection | DOAJ |
| description | Abstract Background B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor T-cell (CAR T-cell) therapy has exhibited remarkable efficacy in refractory or relapsed multiple myeloma (R/R MM), but recurrence and rapid progression of disease are still observed within a short time after treatment. Long-term pomalidomide therapy, which potentiates T-cell functionality, might enhance the efficacy of BCMA CAR T-cell therapy. Methods We performed a single-center retrospective clinical study. Patients with relapsed or refractory multiple myeloma who received BCMA CAR T-cell infusion were enrolled in our study, and were followed by long-term pomalidomide treatment (4 mg/day) or not one month after infusion. The response and adverse events were assessed after infusion. The effect of pomalidomide on BCMA CAR T-cells was assessed in vitro. Results The objective response rate (ORR) of BCMA-CART was 100%. Three months following CAR T-cell infusion, of the 8 patients receiving pomalidomide, except for 2 patients who stopped maintenance therapy and were lost to follow-up, all patients (6/6) achieved VGPR (very good partial response) or CR (complete response), while only 5 patients (5/8) who did not receive pomalidomide treatment achieved VGPR or better. At a median follow-up of 27 months, for the 8 patients who did not receive pomalidomide administration, the median TTP (time to progression) was 5.85 (1–14) months, while the OS (overall survival) was 10.7 (1.2–16) months. Of the 8 patients who received pomalidomide therapy after CAR T-cell infusion, the median TTP was 13 (7–13) months, while the OS was not reached. Moreover, neither long-term hematological toxicity nor drug-induced liver damage was observed during the follow-up period. Mechanistically, pomalidomide promotes antimyeloma efficacy of BCMA CAR T-cells by inhibiting cell apoptosis and enhancing cytoxicity. Conclusions Our results confirmed that BCMA CAR T-cell therapy combined with long-term pomalidomide had a low recurrence rate and manageable therapy-related side effects, providing a promising option for treating R/R MM. Graphical Abstract |
| format | Article |
| id | doaj-art-a60950bfb0a443be87c9a362b63aaf60 |
| institution | DOAJ |
| issn | 1479-5876 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-a60950bfb0a443be87c9a362b63aaf602025-08-20T02:49:09ZengBMCJournal of Translational Medicine1479-58762024-11-0122111310.1186/s12967-024-05772-wBCMA CAR-T therapy combined with pomalidomide is a safe and effective treatment for relapsed/refractory multiple myelomaYuhan Yan0Yixuan Tu1Qian Cheng2Jian Zhang3Erhua Wang4Zuqun Deng5Yan Yu6Liwen Wang7Rui Liu8Ling Chu9Liqing Kang10Jing Liu11Xin Li12Department of Hematology, The Third Xiangya Hospital, Central South UniversityDepartment of Hematology, The Third Xiangya Hospital, Central South UniversityDepartment of Hematology, The Third Xiangya Hospital, Central South UniversityDepartment of Hematology, The Third Xiangya Hospital, Central South UniversityDepartment of Hematology, The Third Xiangya Hospital, Central South UniversityDepartment of Hematology, The Third Xiangya Hospital, Central South UniversityDepartment of Hematology, The Third Xiangya Hospital, Central South UniversityDepartment of Hematology, The Third Xiangya Hospital, Central South UniversityDepartment of Hematology, The Third Xiangya Hospital, Central South UniversityDepartment of Pathology, The Third Xiangya Hospital, Central South UniversityShanghai Unicar-Therapy Bio-Medicine Technology CoDepartment of Hematology, The Third Xiangya Hospital, Central South UniversityDepartment of Hematology, The Third Xiangya Hospital, Central South UniversityAbstract Background B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor T-cell (CAR T-cell) therapy has exhibited remarkable efficacy in refractory or relapsed multiple myeloma (R/R MM), but recurrence and rapid progression of disease are still observed within a short time after treatment. Long-term pomalidomide therapy, which potentiates T-cell functionality, might enhance the efficacy of BCMA CAR T-cell therapy. Methods We performed a single-center retrospective clinical study. Patients with relapsed or refractory multiple myeloma who received BCMA CAR T-cell infusion were enrolled in our study, and were followed by long-term pomalidomide treatment (4 mg/day) or not one month after infusion. The response and adverse events were assessed after infusion. The effect of pomalidomide on BCMA CAR T-cells was assessed in vitro. Results The objective response rate (ORR) of BCMA-CART was 100%. Three months following CAR T-cell infusion, of the 8 patients receiving pomalidomide, except for 2 patients who stopped maintenance therapy and were lost to follow-up, all patients (6/6) achieved VGPR (very good partial response) or CR (complete response), while only 5 patients (5/8) who did not receive pomalidomide treatment achieved VGPR or better. At a median follow-up of 27 months, for the 8 patients who did not receive pomalidomide administration, the median TTP (time to progression) was 5.85 (1–14) months, while the OS (overall survival) was 10.7 (1.2–16) months. Of the 8 patients who received pomalidomide therapy after CAR T-cell infusion, the median TTP was 13 (7–13) months, while the OS was not reached. Moreover, neither long-term hematological toxicity nor drug-induced liver damage was observed during the follow-up period. Mechanistically, pomalidomide promotes antimyeloma efficacy of BCMA CAR T-cells by inhibiting cell apoptosis and enhancing cytoxicity. Conclusions Our results confirmed that BCMA CAR T-cell therapy combined with long-term pomalidomide had a low recurrence rate and manageable therapy-related side effects, providing a promising option for treating R/R MM. Graphical Abstracthttps://doi.org/10.1186/s12967-024-05772-wRelapsed/Refractory multiple myeloma (R/R MM)BCMA CAR T-cell therapyPomalidomideCombination therapy |
| spellingShingle | Yuhan Yan Yixuan Tu Qian Cheng Jian Zhang Erhua Wang Zuqun Deng Yan Yu Liwen Wang Rui Liu Ling Chu Liqing Kang Jing Liu Xin Li BCMA CAR-T therapy combined with pomalidomide is a safe and effective treatment for relapsed/refractory multiple myeloma Journal of Translational Medicine Relapsed/Refractory multiple myeloma (R/R MM) BCMA CAR T-cell therapy Pomalidomide Combination therapy |
| title | BCMA CAR-T therapy combined with pomalidomide is a safe and effective treatment for relapsed/refractory multiple myeloma |
| title_full | BCMA CAR-T therapy combined with pomalidomide is a safe and effective treatment for relapsed/refractory multiple myeloma |
| title_fullStr | BCMA CAR-T therapy combined with pomalidomide is a safe and effective treatment for relapsed/refractory multiple myeloma |
| title_full_unstemmed | BCMA CAR-T therapy combined with pomalidomide is a safe and effective treatment for relapsed/refractory multiple myeloma |
| title_short | BCMA CAR-T therapy combined with pomalidomide is a safe and effective treatment for relapsed/refractory multiple myeloma |
| title_sort | bcma car t therapy combined with pomalidomide is a safe and effective treatment for relapsed refractory multiple myeloma |
| topic | Relapsed/Refractory multiple myeloma (R/R MM) BCMA CAR T-cell therapy Pomalidomide Combination therapy |
| url | https://doi.org/10.1186/s12967-024-05772-w |
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