TY - JOUR
T1 - Bridging Radiation Therapy Before Commercial Chimeric Antigen Receptor T-Cell Therapy for Relapsed or Refractory Aggressive B-Cell Lymphoma
AU - Wright, Christopher M.
AU - LaRiviere, Michael J.
AU - Baron, Jonathan A.
AU - Uche, Chibueze
AU - Xiao, Ying
AU - Arscott, W. Tristram
AU - Anstadt, Emily J.
AU - Barsky, Andrew R.
AU - Miller, David
AU - LaRose, Meredith I.
AU - Landsburg, Daniel J.
AU - Svoboda, Jakub
AU - Nasta, Sunita D.
AU - Gerson, James N.
AU - Barta, Stefan K.
AU - Chong, Elise A.
AU - Schuster, Stephen J.
AU - Paydar, Ima
AU - Maity, Amit
AU - Plastaras, John P.
N1 - Funding Information:
Disclosures: S.K.B. reports grants from Takeda, Merck, Bayer, Celgene, and Seattle Genetics and personal fees from Seattle Genetics, Mundipharma, and Monsanto. E.A.C. reports personal fees and other from Novartis, personal fees and other from Tessa, outside of this study, and has a patent considered by Novartis for combination of RT and CART pending. S.J.S. reports grants, personal fees, and other from Novartis, during the conduct of a study; personal fees from Pfizer, Nordic, Nanovector, Celgene, Gilead, Merck, Novartis, Pharmacyclics, Loxo Oncology, Acerta, and AstraZeneca; grants from Acerta, Celgene, Genentech, Gilead, Merck, Novartis, and Pharmacyclics, outside the submitted work; and has a patent considered by Novartis for combination of RT and CART pending. A.M. reports funding support from Merck for a clinical trial outside the scope of this study. J.P.P. has a patent considered by Novartis for combination of RT and CART pending. All other authors: No conflicts of interest.
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/9/1
Y1 - 2020/9/1
N2 - Purpose: CD19-targeting chimeric antigen receptor T-cell (CART) therapy has emerged as a promising treatment for relapsed/refractory aggressive B-cell lymphoma (r/rABL), culminating in 2 US Food and Drug Administration–approved therapies: tisagenlecleucel (tisa-cel) and axicabtagene ciloleucel (axi-cel). Following leukapheresis and in preparation for CART infusion, contemporary bridging and lymphodepletion regimens rely mostly on cytotoxic chemotherapy. Here, in a cohort of patients treated with commercial tisa-cel and axi-cel, we show that bridging-RT may offer a supplemental approach. Methods and Materials: Thirty-one patients receiving commercial tisa-cel (n = 13) or axi-cel (n = 18) between August 2018 and February 2019 for r/rABL were retrospectively reviewed. Patients were categorized into 2 groups: (1) bridging-RT within 30 days of CART infusion or (2) nonbridging-RT (NBRT), in which patients received either remote RT greater than 30 days before CART infusion or no prior RT. Results: Five patients received bridging-RT within 30 days of CART infusion. Median bridging-RT dose was 37.5 Gy and was completed a median of 13 days before infusion. No grade 3 (G3) or higher RT-toxicities occurred. No patients in the bridging-RT group experienced G3 or higher CART-related toxicities (CRS or neurotoxicity), and 23% (n = 6) and 15% (n = 4) experienced G3-5 CRS and G3-5 neurotoxicity in the NBRT group, respectively. Overall treatment response in the bridging-RT and NBRT groups was 80% and 64%, respectively. The axi-cel CART product was associated with CRS (odds ratio [OR] = 26.67, P =.001) and CRS correlated with neurotoxicity (OR = 12.22, P =.028). There was a trend toward an association for CRS with metabolic tumor volume (OR = 1.06/mL, P =.141) and TLG (OR = 1.01/mL x standard uptake value, P =.099). Conclusions: Bridging-RT before commercial CART does not appear to increase the risk for CART-related toxicities or negatively affect outcomes in r/rABL patients. No G3 or higher RT-toxicities occurred in this series. Pretreatment metabolic tumor burden may be associated with CART-associated CRS; however, larger patient numbers are required to elucidate significant associations. Future work to prospectively assess the value of bridging-RT is warranted.
AB - Purpose: CD19-targeting chimeric antigen receptor T-cell (CART) therapy has emerged as a promising treatment for relapsed/refractory aggressive B-cell lymphoma (r/rABL), culminating in 2 US Food and Drug Administration–approved therapies: tisagenlecleucel (tisa-cel) and axicabtagene ciloleucel (axi-cel). Following leukapheresis and in preparation for CART infusion, contemporary bridging and lymphodepletion regimens rely mostly on cytotoxic chemotherapy. Here, in a cohort of patients treated with commercial tisa-cel and axi-cel, we show that bridging-RT may offer a supplemental approach. Methods and Materials: Thirty-one patients receiving commercial tisa-cel (n = 13) or axi-cel (n = 18) between August 2018 and February 2019 for r/rABL were retrospectively reviewed. Patients were categorized into 2 groups: (1) bridging-RT within 30 days of CART infusion or (2) nonbridging-RT (NBRT), in which patients received either remote RT greater than 30 days before CART infusion or no prior RT. Results: Five patients received bridging-RT within 30 days of CART infusion. Median bridging-RT dose was 37.5 Gy and was completed a median of 13 days before infusion. No grade 3 (G3) or higher RT-toxicities occurred. No patients in the bridging-RT group experienced G3 or higher CART-related toxicities (CRS or neurotoxicity), and 23% (n = 6) and 15% (n = 4) experienced G3-5 CRS and G3-5 neurotoxicity in the NBRT group, respectively. Overall treatment response in the bridging-RT and NBRT groups was 80% and 64%, respectively. The axi-cel CART product was associated with CRS (odds ratio [OR] = 26.67, P =.001) and CRS correlated with neurotoxicity (OR = 12.22, P =.028). There was a trend toward an association for CRS with metabolic tumor volume (OR = 1.06/mL, P =.141) and TLG (OR = 1.01/mL x standard uptake value, P =.099). Conclusions: Bridging-RT before commercial CART does not appear to increase the risk for CART-related toxicities or negatively affect outcomes in r/rABL patients. No G3 or higher RT-toxicities occurred in this series. Pretreatment metabolic tumor burden may be associated with CART-associated CRS; however, larger patient numbers are required to elucidate significant associations. Future work to prospectively assess the value of bridging-RT is warranted.
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U2 - 10.1016/j.ijrobp.2020.05.014
DO - 10.1016/j.ijrobp.2020.05.014
M3 - Article
C2 - 32446950
AN - SCOPUS:85088090876
SN - 0360-3016
VL - 108
SP - 178
EP - 188
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 1
ER -