Prognostic Significance of Positron Emission Tomography Delta Radiomics Following Bridging Therapy in Patients with Large B-Cell Lymphoma Undergoing CAR T-Cell Therapy

Abstract

CAR T-cell therapy is routinely used as a treatment option for relapsed/refractory large B-cell lymphoma (LBCL). Bridging therapy radiation therapy (bRT) is increasingly being utilized prior to chimeric antigen receptor (CAR) T-cell therapy for large B-cell lymphoma (LBCL). It is unknown how the extent of debulking as a result of bRT impacts outcomes following CAR T-cell infusion. We hypothesized that the extent of debulking is prognostic of overall response to therapy. We reviewed patients with LBCL treated with bRT followed by commercially available CAR T-cell therapy between 2017 and 2022. Patients required a F-fluorodeoxyglucose (FDG) positron emission tomography (PET) scan prior to bRT and between completion of bRT and CAR T-cell infusion. On each scan, metabolic tumor volume (MTV), maximum standardized uptake value (SUVmax), SUVmean, and total lesion glycolysis (TLG) were determined. Delta-radiomics based on changes of these values between scans in patients overall and irradiated sites were then calculated. Optimal cut points were determined using maximally selected log-rank. The primary endpoints were progression-free survival (PFS) and local control (LC), measured from CAR T-cell infusion by Kaplan-Meier and Fine-Gray competing risk survival analyses, respectively. Twenty-three patients with LBCL with 33 irradiated sites were reviewed. All metabolically active disease was treated in 10 patients. Median equivalent dose in 2 Gy fractions (EQD2) was 26 Gy (14-44). Median interval from bRT to PET was 9 days (2-30). Following bRT, 2 patients achieved complete responses, 16 had partial responses, and 5 had progressive disease. Five irradiated sites progressed through bRT. No local failures were observed when EQD2>32.5 Gy was given. LC was improved with EQD2>20 Gy (24 mo LC: 94.5% vs 68.6%; p = 0.075). Following BRT, median overall decreases in MTV, SUVmax, SUVmean, and TLG were 22.2 cc (63.1%), 8.9 (36.8%), 3.4 (31.1%), and 297.9 cc (75.8%), respectively. Median decreases in MTV, SUVmax, SUVmean, and TLG in irradiated sites were 15.6 cc (91.1%), 17.0 (74.6%), 6.8 (55.3%), and 157.0 cc (94.6%), respectively. PFS was significantly improved in patients with reductions of MTV of at least 36 cc (24 mo PFS: 69.2% vs 0%; p = 0.047) or SUVmax of at least 15 (24-mo PFS: 80.0% vs 28.1%; p < 0.001). LC was significantly improved in lesions with reductions of SUVmax of at least 14 (24-mo LC: 100% vs 67.3%; p < 0.001) or SUVmean of at least 7 (24-mo LC: 100% vs 74.4%; p < 0.001). bRT led to significant reductions in MTV, SUVmax, SUVmean, and TLG. The extent of these decreases correlated with improved PFS and LC. There appears to be a dose-response relationship. Larger cohorts should validate the value of interim PET following bRT, and associated changes in disease burden as a means of prognosticating patients. Future work might evaluate whether escalation of BT in patients with suboptimal response, using either systemic therapy or higher radiation doses, has an impact on outcomes.