Bridging therapy with axicabtagene ciloleucel for large B-cell lymphoma: results from the US Lymphoma CAR-T Consortium

Abstract

During the manufacturing period of autologous chimeric antigen receptor (CAR) T-cell therapy, patients may experience a decline in their condition due to cancer progression. In this study, we investigated the impact of bridging therapy (BT) on the outcome of patients with relapsed/refractory large B-cell lymphoma who received antilymphoma treatment between leukapheresis and axicabtagene ciloleucel (axi-cel) infusion. We conducted our analysis using data from the multicenter US Lymphoma CAR-T Consortium, with a median follow-up of 33 months (range, 4.3-42.1). Out of the 298 patients who underwent leukapheresis, 275 patients received axi-cel. A total 52% of patients (n = 143) who received BT had a higher baseline risk profile than patients who did not receive BT, and these patients, as a group, had inferior outcomes compared with those who did not receive BT. However, after propensity score matching between the 2 groups, there were no statistically significant differences in overall response rate (77% vs 87%; P = .13), complete response rate (58% vs 70%; P = .1), progression-free survival (hazard ratio [HR], 1.25; P = .23), and overall survival (HR, 1.39; P=.09) between the BT group and the no-BT group, respectively. Analyzing the effects of BT in the whole cohort that underwent leukapheresis regardless of receiving axi-cel (intention-to-treat analysis) showed similar results. Radiation BT resulted in outcomes similar to those observed with nonradiation BT. Our findings suggest that BT may be safe without a significant impact on long-term survival for patients who require disease stabilization during the manufacturing period. Moreover, our results suggest that there is no clear advantage to using radiation-based BT over nonradiation-based BT.

Graphical abstract

Figure 1.

Distribution of patients based on BT.

Figure 2.

PFS, OS, and response to axi-cel in the mITT cohort. Kaplan-Meier curves of PFS and OS. Curves start at the time of axi-cel infusion and are stratified according to BT. Unadjusted mITT analyses compare the n = 132 patients without BT with the n = 143 patients who received BT. After PS matching, n = 97 patients were matched and compared in each group. Unadjusted PFS and OS (A,B) and PFS and OS after adjustment for baseline characteristics with PS matching (D,E). The ORR and CR rates in the mITT cohort before matching (C) and after PS matching (F). CART, CAR T-cell therapy.

Figure 3.

Outcome after axi-cel stratified based on the category of BT. Kaplan-Meier curves starting from the time of axi-cel infusion, showing unadjusted PFS (A) and OS (B) comparing patients who received chemotherapy (chemo; n = 72), corticosteroids only (steroids; n = 37), radiation therapy alone (RT; n = 19), and targeted therapies (targeted; n = 15). Kaplan-Meier curves depicting PFS (C) and OS (D) after PS matching stratified based on any RT (n = 24) bridging vs non-RT bridging (n = 44). The ORR and CR rates in RT bridging vs non-RT bridging after PS matching (E).