BCMA-directed CAR T-cell therapy in patients with multiple myeloma and CNS involvement
Abstract: We investigated B-cell maturation antigen-directed chimeric antigen receptor T-cell (CAR-T) therapy in patients with relapsed or refractory multiple myeloma (MM) and central nervous system (CNS) involvement. Ten patients received either idecabtagene vicleucel (n = 6) or ciltacabtagene auto...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-03-01
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| Series: | Blood Advances |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2473952924007493 |
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| author | Mahmoud R. Gaballa Omar Castaneda Puglianini Adam Cohen Dan Vogl Alfred Chung Christopher J. Ferreri Peter Voorhees Doris K. Hansen Krina K. Patel |
| author_facet | Mahmoud R. Gaballa Omar Castaneda Puglianini Adam Cohen Dan Vogl Alfred Chung Christopher J. Ferreri Peter Voorhees Doris K. Hansen Krina K. Patel |
| author_sort | Mahmoud R. Gaballa |
| collection | DOAJ |
| description | Abstract: We investigated B-cell maturation antigen-directed chimeric antigen receptor T-cell (CAR-T) therapy in patients with relapsed or refractory multiple myeloma (MM) and central nervous system (CNS) involvement. Ten patients received either idecabtagene vicleucel (n = 6) or ciltacabtagene autoleucel (n = 4), where brain/cranial nerve and/or spinal cord involvement/leptomeningeal disease were evident on either magnetic resonance imaging (100%) and/or cerebrospinal fluid (40%). Eight patients had their CNS diagnosis before CAR-T therapy, and two were diagnosed within 14 days post-infusion. Seven received CNS-directed therapy during bridging before CAR-T therapy. There were no excess toxicities: no cytokine release syndrome grade ≥3; 10% immune effector cell-associated neurotoxicity syndrome (ICANS) grade 3; and no ICANS grade 4. Two patients experienced delayed but treatable neurotoxicity, with no reported parkinsonian side effects. The best overall response rate was 80% (≥70% very good partial response) and a 100% CNS response. With a median follow-up of 381 days, patients with CNS myeloma diagnosed before CAR-T therapy (n = 8) had a median overall survival and progression-free survival (PFS) of 13.3 and 6.3 months, respectively. Best outcomes were observed in 4 patients who had a response to bridging therapy, suggesting that optimizing pre-CAR-T therapy may be key for improved outcomes. Our study suggests that CAR-T therapy in patients with CNS MM is safe and feasible, and screening for CNS involvement before CAR-T therapy could be warranted in high-risk patients. The excellent initial response but relatively short PFS suggests consideration for post-CAR-T maintenance. Larger studies are needed to confirm these findings. |
| format | Article |
| id | doaj-art-9ee2fb8cfee149c0b781acbfa8cbf411 |
| institution | DOAJ |
| issn | 2473-9529 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Blood Advances |
| spelling | doaj-art-9ee2fb8cfee149c0b781acbfa8cbf4112025-08-20T02:47:21ZengElsevierBlood Advances2473-95292025-03-01951171118010.1182/bloodadvances.2024014345BCMA-directed CAR T-cell therapy in patients with multiple myeloma and CNS involvementMahmoud R. Gaballa0Omar Castaneda Puglianini1Adam Cohen2Dan Vogl3Alfred Chung4Christopher J. Ferreri5Peter Voorhees6Doris K. Hansen7Krina K. Patel8Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TXDepartment of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FLDivision of Hematology-Oncology, Department of Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PADivision of Hematology-Oncology, Department of Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PADivision of Hematology/Oncology, University of CA San Francisco Cancer Center, University of California, San Francisco, CAAtrium Health Wake Forest Baptist Comprehensive Cancer Center, Levine Cancer Institute, Charlotte, NCAtrium Health Wake Forest Baptist Comprehensive Cancer Center, Levine Cancer Institute, Charlotte, NCDepartment of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FLDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX; Correspondence: Krina K. Patel, The University of Texas MD Anderson Cancer Center, Department of Lymphoma and Myeloma, 1515 Holcombe Blvd, Houston, TX 77030;Abstract: We investigated B-cell maturation antigen-directed chimeric antigen receptor T-cell (CAR-T) therapy in patients with relapsed or refractory multiple myeloma (MM) and central nervous system (CNS) involvement. Ten patients received either idecabtagene vicleucel (n = 6) or ciltacabtagene autoleucel (n = 4), where brain/cranial nerve and/or spinal cord involvement/leptomeningeal disease were evident on either magnetic resonance imaging (100%) and/or cerebrospinal fluid (40%). Eight patients had their CNS diagnosis before CAR-T therapy, and two were diagnosed within 14 days post-infusion. Seven received CNS-directed therapy during bridging before CAR-T therapy. There were no excess toxicities: no cytokine release syndrome grade ≥3; 10% immune effector cell-associated neurotoxicity syndrome (ICANS) grade 3; and no ICANS grade 4. Two patients experienced delayed but treatable neurotoxicity, with no reported parkinsonian side effects. The best overall response rate was 80% (≥70% very good partial response) and a 100% CNS response. With a median follow-up of 381 days, patients with CNS myeloma diagnosed before CAR-T therapy (n = 8) had a median overall survival and progression-free survival (PFS) of 13.3 and 6.3 months, respectively. Best outcomes were observed in 4 patients who had a response to bridging therapy, suggesting that optimizing pre-CAR-T therapy may be key for improved outcomes. Our study suggests that CAR-T therapy in patients with CNS MM is safe and feasible, and screening for CNS involvement before CAR-T therapy could be warranted in high-risk patients. The excellent initial response but relatively short PFS suggests consideration for post-CAR-T maintenance. Larger studies are needed to confirm these findings.http://www.sciencedirect.com/science/article/pii/S2473952924007493 |
| spellingShingle | Mahmoud R. Gaballa Omar Castaneda Puglianini Adam Cohen Dan Vogl Alfred Chung Christopher J. Ferreri Peter Voorhees Doris K. Hansen Krina K. Patel BCMA-directed CAR T-cell therapy in patients with multiple myeloma and CNS involvement Blood Advances |
| title | BCMA-directed CAR T-cell therapy in patients with multiple myeloma and CNS involvement |
| title_full | BCMA-directed CAR T-cell therapy in patients with multiple myeloma and CNS involvement |
| title_fullStr | BCMA-directed CAR T-cell therapy in patients with multiple myeloma and CNS involvement |
| title_full_unstemmed | BCMA-directed CAR T-cell therapy in patients with multiple myeloma and CNS involvement |
| title_short | BCMA-directed CAR T-cell therapy in patients with multiple myeloma and CNS involvement |
| title_sort | bcma directed car t cell therapy in patients with multiple myeloma and cns involvement |
| url | http://www.sciencedirect.com/science/article/pii/S2473952924007493 |
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