CNS bridging radiotherapy achieves rapid cytoreduction before CAR T-cell therapy for aggressive B-cell lymphomas Journal Article
| Authors: | Cederquist, G. Y.; Schefflein, J.; Devlin, S. M.; Shah, G. L.; Shouval, R.; Hubbeling, H.; Tringale, K.; Tomas, A. A.; Fregonese, B.; Hajj, C.; Boardman, A.; Luna De Abia, A.; Corona, M.; Cassanello, G.; Dahi, P. B.; Lin, R. J.; Ghione, P.; Salles, G.; Perales, M. A.; Palomba, M. L.; Falchi, L.; Scordo, M.; Grommes, C.; Yahalom, J.; Imber, B. S. |
| Article Title: | CNS bridging radiotherapy achieves rapid cytoreduction before CAR T-cell therapy for aggressive B-cell lymphomas |
| 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. |
| Keywords: | adult; clinical article; aged; middle aged; fatigue; systemic therapy; cancer radiotherapy; cytarabine; methotrexate; rituximab; nuclear magnetic resonance imaging; outcome assessment; cytoreductive surgery; mantle cell lymphoma; cohort analysis; bendamustine; cyclophosphamide; hematopoietic stem cell transplantation; central nervous system tumor; b cell lymphoma; cerebrospinal fluid; cognitive defect; dermatitis; headache; burkitt lymphoma; non-hodgkin lymphoma; clinical target volume; leukapheresis; cervical spinal cord; cytokine release syndrome; tocilizumab; ibrutinib; human; male; female; article; pembrolizumab; venetoclax; tisagenlecleucel t; chimeric antigen receptor t-cell immunotherapy; lisocabtagene maraleucel; immune effector cell associated neurotoxicity syndrome; toxicity and intoxication; central nervous system bridging radiotherapy |
| Journal Title: | Blood Advances |
| Volume: | 8 |
| Issue: | 19 |
| ISSN: | 2473-9529 |
| Publisher: | American Society of Hematology |
| Date Published: | 2024-10-09 |
| Start Page: | 5192 |
| End Page: | 5199 |
| Language: | English |
| DOI: | 10.1182/bloodadvances.2024013393 |
| PUBMED: | 38861344 |
| PROVIDER: | scopus |
| PMCID: | PMC11530392 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Group (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Brandon Imber -- Source: Scopus |
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