Bridging Radiation Rapidly and Effectively Cytoreduces High-Risk Relapsed/Refractory Aggressive B Cell Lymphomas Prior to Chimeric Antigen Receptor T Cell Therapy

Harper Hubbeling, Emily A. Silverman, Laure Michaud, Ana Alarcon Tomas, Roni Shouval, Jessica Flynn, Sean Devlin, N. Ari Wijetunga, Kathryn R. Tringale, Connie Batlevi, Parastoo Dahi, Sergio Giralt, Richard Lin, Jae Park, Michael Scordo, Craig Sauter, Gunjan Shah, Carla Hajj, Gilles Salles, Heiko SchoderM. Lia Palomba, Miguel Angel Perales, Joachim Yahalom, Brandon S. Imber*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)259.e1-259.e10
JournalTransplantation and Cellular Therapy
Volume29
Issue number4
DOIs
StatePublished - Apr 2023
Externally publishedYes

Keywords

  • Bridging
  • Chimeric antigen receptor T cell
  • Diffuse large B cell lymphoma
  • Lymphoma
  • Radiation

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