Bridging Radiation Therapy Before Commercial Chimeric Antigen Receptor T-Cell Therapy for Relapsed or Refractory Aggressive B-Cell Lymphoma

Christopher M. Wright, Michael J. LaRiviere, Jonathan A. Baron, Chibueze Uche, Ying Xiao, W. Tristram Arscott, Emily J. Anstadt, Andrew R. Barsky, David Miller, Meredith I. LaRose, Daniel J. Landsburg, Jakub Svoboda, Sunita D. Nasta, James N. Gerson, Stefan K. Barta, Elise A. Chong, Stephen J. Schuster, Ima Paydar, Amit Maity, John P. Plastaras

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)178-188
Number of pages11
JournalInternational Journal of Radiation Oncology Biology Physics
Volume108
Issue number1
DOIs
StatePublished - Sep 1 2020

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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