Association of bridging therapy utilization with clinical outcomes in patients receiving chimeric antigen receptor (CAR) T-cell therapy

Background: Chimeric antigen receptor (CAR) T-cell therapy recipients may receive bridging therapy while awaiting product manufacturing to control disease. Yet, data are lacking regarding the impact of bridging therapy use on clinical outcomes. Methods: We conducted a retrospective analysis of 235 patients who received CAR T-cell therapy at two tertiary care centers from February 2016 to December 2019. We abstracted clinical outcomes from review of the electronic health record including (1) overall response; (2) complete response (CR); (3) progression-free survival (PFS); (4) overall survival (OS); and (5) toxicity (cytokine release syndrome (CRS) and neurotoxicity). We assessed the association of bridging therapy use with overall response rate (ORR) and CR rate using multivariable logistic regression and with PFS and OS using multivariable Cox regression controlling for covariates. We analyzed the association of bridging therapy use with CRS and neurotoxicity using Fisher's exact test. Results: Patients' median age was 63.1 years (range: 19-82), and the majority were men (144/235, 61.3%). Most patients received axicabtagene ciloleucel (192/235, 81.7%), and the most common lymphoma subtype was diffuse large B-cell lymphoma or grade 3B follicular lymphoma (107/235, 45.5%). Overall, 39.4% (93/236) received bridging therapy. Bridging therapy regimens included systemic chemotherapy (48/92, 52.2%), corticosteroids (25/92, 27.2%), radiation (9/92, 9.8%), and other systemic therapies (10/92, 10.9%). In multivariable Cox regression, bridging therapy use was associated with OS (HR: 1.97, p=0.004) but not PFS (HR: 1.18, p=0.449). In multivariable logistic regression, bridging therapy use was not associated with ORR (OR: 0.69, p=0.391) or CR rate (OR: 0.96, p=0.901). We did not identify an association of bridging therapy use with grade 3+ CRS (p=0.574) or grade 3+ neurotoxicity (p=0.748). Conclusions: We identified that bridging therapy use is not associated with differences in ORR, CR rate, or PFS but is associated with worse OS. These data suggest bridging therapy may be a surrogate for additional poor prognostic factors leading to inferior OS and underscore the need for novel bridging therapy regimens to optimize outcomes in this patient population.