Analysis of Patterns of Failure and the Role of Bridging Radiation Therapy in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL) Treated with CAR T-Cell Therapy

Abstract

Bridging therapy (BT) with chemotherapy, targeted therapy, and/or radiation therapy (RT) is often administered to aid in tumor debulking or control symptomatic disease prior to CAR T-cell therapy (CAR-T). However, little is known about the optimal type of BT and the impact BT may have on patterns of failure. We sought to compare the patterns of failure in patients who received CAR-T for R/R NHL based on the type of BT received. We hypothesize that bridging RT decreases the risk of local recurrence in sites treated with RT prior to CAR-T therapy.An IRB-approved single-institution retrospective review was performed of all R/R DLBCL patients who underwent CAR-T with axicabtagene ciloleucel and had PET/CT scans immediately before, D+30, and D+90 post-CAR-T available for review. PET/CTs were analyzed with response assessment per the Lugano classification. FDG-avid (Lugano 4 or 5) lesions on the pre-CAR-T scan were recorded as index lesions and compared to residual or new FDG-avid lesions on post-CAR-T scans.20 patients met inclusion criteria, of whom 6 were treated with no BT, 8 with bridging chemotherapy, 5 with bridging RT (median 30 Gy in 10 fxs), and 1 with a Bruton's tyrosine-kinase inhibitor (BTKi). At last follow up, 13/19 (68%) were alive (4/6 with no BT, 5/7 with chemo, 3/5 with RT, 1/1 with BTKi) and 7/19 (37%) were without disease progression (2/6 with no BT, 4/7 with chemo, 1/5 with RT, 0/1 with BTKi); one patient was lost to follow up. 9 patients (45%) had metabolic complete response (CR) at D+30 and 8 (40%) at D+90. Based on type of BT received, D+90 CR rates were 50% for no BT, 57% for chemo, and 25% for RT. In analysis of patterns of failure, there were 67 total index lesions identified on pre-CAR-T PET/CT scans. Of those, 26 received no BT, 28 were treated with bridging chemotherapy, 7 with bridging RT, 6 with BTKi. On D+30 PET/CT, the rates of CR were 18/26 (69%) in lesions without BT, 21/28 (75%) in lesions treated with chemo, 6/7 (86%) in lesions with RT. By D+90, the rates of CR were 17/22 (77%) in lesions without BT, 18/22 (82%) in lesions treated with chemo, and 4/4 (100%) of lesions treated with RT. Of the 56 lesions noted on D+30 PET/CTs, 24 (43%) were index lesions on pre-CAR-T PET/CT, and only 8 (22%) of the lesions on D+90 PET/CT were initial index lesions.Patients who require BT before CAR-T have higher relapse rates, likely reflecting more aggressive disease biology. Bridging RT to CAR-T appears to be safe and effective in providing local control, even at palliative doses, but may not impact overall outcomes. Radiating all sites of active disease pre-CAR-T may not improve outcomes as the predominant pattern of failure appears to be distant. However, these data suggest that bridging RT should be considered in sites where local control is a priority, such as symptomatic sites or sites where recurrence may cause significant morbidity. The optimal timing and combination strategies with RT and CAR-T for R/R DLBCL needs to be explored prospectively.