Categorization and Impact of Bridging Therapy Prior to CAR T-Cell Infusion in Patients with Relapsed/Refractory Non-Hodgkin Lymphoma

Title: Categorization and Impact of Bridging Therapy prior to CAR T-cell Infusion in patients with Relapsed/Refractory non-Hodgkin Lymphoma Introduction: Bridging therapy (BT) has served to provide disease control and symptom stabilization in patients with recurrent non-Hodgkin lymphoma prior to CD-19 directed chimeric antigen receptor t-cell therapy (CART). However, there is no standard approach to identifying the need and most appropriate type of BT, and the benefits of improved disease control may or may not be outweighed by the short and long-term toxicities associated with BT. We utilized a national consortium to identify predictors of receipt of BT, the type of BT utilized, and its impact on survival outcomes. Methods: We analyzed patients enrolled in the Lymphoma Innovations ORIEN Network (LION) cohort, a consortium of 7 US academic institutions. All patients had received CART for relapsed or refractory NHL, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). Patients were categorized based on receipt of BT (defined as receipt of any anti-lymphoma therapy between the apheresis date and date of initiation of lymphodepleting therapy) and type of BT given (chemotherapy-based or non-chemotherapy-containing). We compared demographics and treatment-related variables of interest between groups to identify predictors of receipt of BT and type of BT. To assign risk groups (low, intermediate, and high) we used Revised International Prognostic Indices (R-IPI) for DLBCL, MCL-IPI (MIPI) and Follicular Lympoma IPI (FLIPI). R-IPI scores of 0-1 were considered low risk, 2-3 as intermediate risk and four and above as high risk. FLIPI scores of 0-1 were low risk, 2 as intermediate risk and 3 and above as high risk. Primary outcomes included PFS and OS between groups that received BT and those that did not. Secondary outcomes included PFS and OS between risk groups, outcomes between chemotherapy vs non-chemotherapy BT groups, and duration of response to salvage therapy. Results: Of 287 patients, 176 received BT and 111 did not. 184 patients were treated for DLBCL, 52 for FL and 44 for MCL. 55 patients were classified as low risk, 97 as intermediate risk and 89 as high risk. Amongst those who received BT, 86 received chemotherapy-based BT and 91 received non-chemotherapy containing BT. Median follow up time for the overall cohort after receipt of CART was 1.54 years (95% CI, 1.34-1.81). Median PFS for the group that did not receive BT was 1.7 years (95% CI, 1.0-3.5) and 0.9 years for those that did receive BT (95% CI, 0.6-1.4, p=0.046). Median OS for the group that did not receive BT was 4 years (95% CI, 4-NA) and was 2.9 years for the group that received BT (95% CI, 1.9-NA, p=0.073). Median PFS for the chemotherapy-based BT group was 0.6 years (95% CI 0.3-1.0) and for non-chemotherapy BT was 1.2 years (95% CI, 0.8-NA, p=0.06). Median OS for the chemotherapy-based BT group was 2.5 years (95% CI, 1.6-NA) and median OS for the non-chemotherapy BT group was 3.1 years (95% CI, 1.8-NA, p=0.49). Univariate analysis revealed no association between risk group designation and receipt of BT. Pairwise comparison demonstrated that those who received chemotherapy-based BT had significantly worse PFS than those who did not receive BT (p=0.008). Conclusion: BT was used in > 50% of patients completing CAR-T for relapsed/refractory NHL. Although there appeared to be a possible improvement in PFS for patients who received a non-chemotherapy-containing BT, this was not statistically significant. Additionally, there was no association between risk group and receipt of BT, suggesting that other factors may be impacting therapy selection. Future research is needed to identify the optimal candidates for BT.