Don't put the CART before the horse: The role of radiation therapy in peri-CAR T-cell therapy for aggressive B-cell non-Hodgkin lymphoma

The optimal approach to incorporate radiotherapy (RT) in conjunction with CAR T-cell Therapy (CART) for relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (bNHL) remains unclear. This study documents the RT local control rate among patients who received bridging radiotherapy (BRT) prior to CART and compares it to those who received salvage radiotherapy (SRT) post CART. It further reports on a promising way to utilize SRT for post CART disease, and identifies predictors for RT in-field recurrence.We retrospectively reviewed 83 patients with r/r bNHL who received CART and RT, either as BRT pre-CART infusion (n=35) or as SRT post-CART infusion (n=48), between 2018 and 2021. RT was defined as comprehensive (compRT) - treated all sites of active disease - or focal (focRT). Limited disease was defined as disease amenable to compRT, involving5 active disease sites.At time of RT, patients who received BRT prior to CART had bulkier disease sites (median diameter 8.7cm vs. 5.5cm; p=0.01) and were treated to significantly lower doses (median equivalent 2 Gy dose 23.3Gy vs. 34.5Gy, p=0.002), compared to SRT post CART. Among 124 total irradiated sites identified, 8/59 (13%) bridged-sites and 21/65 (32%) salvaged-sites experienced in-field recurrence translating to 1-year local control rate (LC) of 84% and 62%, respectively (p=0.009). Patients with limited post-CART disease (n=37) who received compSRT (n=26) had better overall survival (51% vs. 12%; p=0.028), freedom from subsequent progression (31% vs. 0%; p0.001) and freedom from subsequent event (19% vs. 0%; p=0.011) compared to patients with limited disease who received focSRT (n=11).BRT followed by CART appears to be associated with improved LC compared to SRT in r/r bNHL. Nonetheless, SRT offers a promising salvage intervention for limited (5 sites) relapsed post-CART disease if given comprehensively.