CNS bridging radiotherapy achieves rapid cytoreduction before CAR T-cell therapy for aggressive B-cell lymphomas.

Autor:	Cederquist GY; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY., Schefflein J; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY., Devlin SM; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY., Shah GL; Department of Medicine, Adult Bone Marrow Transplant Service, Cellular Therapy Service, Memorial Sloan Kettering Cancer Center, New York, NY.; Department of Medicine, Weill Cornell Medical College, New York, NY., Shouval R; Department of Medicine, Adult Bone Marrow Transplant Service, Cellular Therapy Service, Memorial Sloan Kettering Cancer Center, New York, NY.; Department of Medicine, Weill Cornell Medical College, New York, NY.; Department of Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel., Hubbeling H; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.; Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA., Tringale K; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.; Department of Radiation Medicine and Applied Sciences, UC San Diego, La Jolla, CA., Alarcon Tomas A; Department of Medicine, Adult Bone Marrow Transplant Service, Cellular Therapy Service, Memorial Sloan Kettering Cancer Center, New York, NY.; Hematology and Hemotherapy Service, Hospital Universitario Gregorio Marañón, Madrid, Spain., Fregonese B; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY., Hajj C; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY., Boardman A; Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY., Luna De Abia A; Department of Medicine, Adult Bone Marrow Transplant Service, Cellular Therapy Service, Memorial Sloan Kettering Cancer Center, New York, NY.; Adult Bone Marrow Transplantation Unit, Hospital Universitario Ramón y Cajal, Madrid, Spain., Corona M; Department of Medicine, Adult Bone Marrow Transplant Service, Cellular Therapy Service, Memorial Sloan Kettering Cancer Center, New York, NY., Cassanello G; Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy., Dahi PB; Department of Medicine, Adult Bone Marrow Transplant Service, Cellular Therapy Service, Memorial Sloan Kettering Cancer Center, New York, NY.; Department of Medicine, Weill Cornell Medical College, New York, NY., Lin RJ; Department of Medicine, Adult Bone Marrow Transplant Service, Cellular Therapy Service, Memorial Sloan Kettering Cancer Center, New York, NY., Ghione P; Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY., Salles G; Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY., Perales MA; Department of Medicine, Adult Bone Marrow Transplant Service, Cellular Therapy Service, Memorial Sloan Kettering Cancer Center, New York, NY.; Department of Medicine, Weill Cornell Medical College, New York, NY., Palomba ML; Department of Medicine, Weill Cornell Medical College, New York, NY.; Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY., Falchi L; Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY., Scordo M; Department of Medicine, Adult Bone Marrow Transplant Service, Cellular Therapy Service, Memorial Sloan Kettering Cancer Center, New York, NY., Grommes C; Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY., Yahalom J; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY., Imber BS; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.; Department of Medicine, Early Drug Development Service, Memorial Sloan Kettering Cancer Center, New York, NY.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2024 Oct 08; Vol. 8 (19), pp. 5192-5199.
DOI:	10.1182/bloodadvances.2024013393
Abstrakt:	Abstract: Chimeric antigen receptor (CAR) T-cell therapy (CART) for central nervous system lymphoma (CNSL) is a promising strategy, yet responses are frequently not durable. Bridging radiotherapy (BRT) is used for extracranial lymphoma in which it can improve CART outcomes through cytoreduction of high-risk lesions. We hypothesized that BRT would achieve similar, significant cytoreduction before CART for CNSL (CNS-BRT). We identified patients with CNSL with non-Hodgkin B-cell lymphoma who received CNS-BRT before commercial CART. Cytoreduction from CNS-BRT was calculated as change in lesion size before CART. Twelve patients received CNS-BRT, and the median follow-up among survivors is 11.8 months (interquartile range, 8.5-21.9). Ten patients had CNSL (9 secondary, 1 primary) and 2 patients had epidural disease (evaluable for toxicity). All 10 patients with CNSL had progressive disease at the time of CNS-BRT. Of 12 patients, 1 experienced grade ≥3 cytokine release syndrome, and 3 of 12 patients experienced grade ≥3 immune effector cell-associated neurotoxicity syndrome. CNS-BRT achieved a 74.0% (95% confidence interval, 62.0-86.0) mean reduction in lesion size from baseline (P = .014) at a median of 12 days from BRT completion and before CART infusion. Best CNS response included 8 complete responses, 1 partial response, and 1 progressive disease. Three patients experienced CNS relapse outside the BRT field. Preliminary data suggest CNS-BRT achieves rapid cytoreduction and is associated with a favorable CNS response and safety profile. These data support further study of BRT as a bridging modality for CNSL CART. (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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