Bridging radiation rapidly and effectively cytoreduces high-risk relapsed/refractory aggressive B cell lymphomas prior to chimeric antigen receptor T cell therapy Journal Article
| Authors: | Hubbeling, H.; Silverman, E. A.; Michaud, L.; Tomas, A. A.; Shouval, R.; Flynn, J.; Devlin, S.; Wijetunga, N. A.; Tringale, K. R.; Batlevi, C.; Dahi, P.; Giralt, S.; Lin, R.; Park, J.; Scordo, M.; Sauter, C.; Shah, G.; Hajj, C.; Salles, G.; Schoder, H.; Palomba, M. L.; Perales, M. A.; Yahalom, J.; Imber, B. S. |
| Article Title: | Bridging radiation rapidly and effectively cytoreduces high-risk relapsed/refractory aggressive B cell lymphomas prior to chimeric antigen receptor T cell therapy |
| Abstract: | Greater tumor burden before CD19-targeted chimeric antigen receptor T cell (CAR-T) therapy predicts lower complete response rate and shorter overall survival (OS) in patients with aggressive non-Hodgkin lymphoma (NHL). Recent patterns of failure studies have identified lesion characteristics, including size, standard uptake value (SUV), and extranodal location, as associated with post-CAR-T therapy failure. Here we analyzed the effect of bridging radiation-containing treatment (BRT) on pre-CAR-T therapy lesion- and patient-level characteristics and post-CAR-T therapy outcomes, including patterns of failure. Consecutive NHL patients who received radiation therapy from 30 days before leukapheresis until CAR T cell infusion were reviewed. Metabolic tumor volume (MTV) was contoured with a threshold SUV of 4. The first post-CAR-T therapy failures were categorized as preexisting/new/mixed with respect to pre-CAR-T therapy disease and in-field/marginal/distant with respect to BRT. Forty-one patients with diffuse large B cell lymphoma (DLBCL; n = 33), mantle cell lymphoma (n = 7), or Burkitt lymphoma (n = 1) were identified. BRT significantly improved established high-risk parameters of post-CAR-T therapy progression, including in-field median MTV (45.5 cc to.2 cc; P <.001), maximum SUV (18.1 to 4.4; P <.001), diameter (5.5 cm to 3.2 cm; P <.001), and lactate dehydrogenase (LDH; 312 to 232; P =.025). DLBCL patients with lower LDH levels post-BRT had improved progression-free survival (PFS; P =.001). In DLBCL, first failures were new in 7 of 19 patients, preexisting in 5 of 19, and mixed in 7 of 19; with respect to BRT, 4 of 19 were in-field and 4 of 19 were marginal. Post-CAR-T therapy survival was similar in patients with initially low MTV and those with newly low MTV post-BRT using a statistically determined threshold of 16 cc (PFS, 26 months versus 31 months; OS unreached for both). BRT produced significant cytoreductions in diameter, SUV, MTV, and LDH, all predictors of poor post-CAR-T therapy outcomes. Similar PFS and OS in patients with initially low MTV and those who achieved newly low MTV after BRT suggest that BRT may “convert” poor-risk patients to better risk. In the future, the response to BRT may allow for risk stratification and individualization of bridging strategies. © 2022 The American Society for Transplantation and Cellular Therapy |
| Keywords: | adult; cancer survival; controlled study; aged; treatment failure; human cell; major clinical study; overall survival; lenalidomide; prednisone; fatigue; cancer recurrence; doxorubicin; gemcitabine; cancer patient; cancer radiotherapy; cytarabine; methotrexate; rituximab; outcome assessment; progression free survival; bortezomib; mantle cell lymphoma; anemia; radiation; mucosa inflammation; thrombocytopenia; cyclophosphamide; dexamethasone; risk assessment; b cell lymphoma; nonhodgkin lymphoma; lymphoma, non-hodgkin; folinic acid; lymphoma; xerostomia; lactate dehydrogenase; dermatitis; lymphoma, large b-cell, diffuse; biological therapy; drug therapy; oxaliplatin; trismus; adoptive immunotherapy; immunotherapy, adoptive; burkitt lymphoma; individualization; adverse event; leukapheresis; diffuse large b cell lymphoma; metabolic tumor volume; maximum standardized uptake value; ibrutinib; humans; human; male; female; article; cell- and tissue-based therapy; venetoclax; chimeric antigen receptor t-cell immunotherapy; zanubrutinib; bridging; receptors, chimeric antigen; chimeric antigen receptor t cell |
| Journal Title: | Transplantation and Cellular Therapy |
| Volume: | 29 |
| Issue: | 4 |
| ISSN: | 2666-6375 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2023-04-01 |
| Start Page: | 259.e1 |
| End Page: | 259.e10 |
| Language: | English |
| DOI: | 10.1016/j.jtct.2022.12.021 |
| PUBMED: | 36587744 |
| PROVIDER: | scopus |
| PMCID: | PMC10089652 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding author is MSK author Brandon S. Imber -- Source: Scopus |
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