P1173: early administration of polatuzumab vedotin as bridging cd19-specific chimeric antigen receptor t cell therapy is an effective strategy to improve survival in patients with r/r b-cell lymphoma

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: The prognosis of refractory/relapsed B-cell lymphoma (r/r B-NHL) is extremely poor, especially for those patients who have failed therapy with CAR -T. Although the benefit was observed with Pola-based salvage therapy, long-term survival was unsatisfactory, particularly in patients who did not intend to bridge to subsequent therapy. Aims: Our objective was to evaluate the efficacy of Pola-based salvage therapy and as a bridge to CAR -T-cell therapy in r/r B-NHL patients, including response rates, progression-free survival (PFS), and overall survival (OS). Methods: We analyzed the use of Pola-based salvage therapy between June 2020 and January 2023.Ninety-four patients were included: 53/94 (56.4%) male; median age 49 (18-80). Diagnoses included DLBCL NOS (n=68), HGBL (n=7), PMBCL (n=5), TFL (n=5), BL (n=6), and other (n=3). 91/94 (96.8%) patients were at stage III-IV at the time of salvage therapy. The median IPI score was 3 (range 1-5). 80/94 (85.1%) patients had extranodal lesions. 34/94 (36.2%) patients had > 7 cm bulky disease. Patients had received a median of 3 (range 1-8) prior lines of treatment. 13/94 (13.8%) and 19/94 (20.2%) patients had failed prior autologous hematopoietic stem cell transplantation and prior anti-CD19 CAR -T cell therapy, respectively. 46/94 (48.9%) patients received Pola-based therapy (salvage cohort) and 48/94 (51.1%) patients were treated with Pola-based therapy as bridging CAR -T-cell therapy (bridging cohort), including 19 patients after failure of prior anti-CD19 CAR -T. The median number of pola-based cycles was 3 (1-8) for the salvage cohort and 3 (1-6) for the bridging cohort. 48/94 (51.1%), 11/94 (11.7%), and 35/94 (37.2%) of patients received PB/PBR, P-GMox/ ICE, and Pola in combination with other chemotherapy regimens, respectively. Prior to the study, the expression of CD19/CD20/CD22/CD79b antigens in tumour tissue was confirmed by pathology and the different CAR targets were selected for patients who failed anti-CD19 CART cell therapy. Results: The best ORR for the salvage and bridging cohorts was 58.54% and 41.46%, respectively (P=0.1164). In the bridging cohort, the ORR was 44.4% for patients who had failed prior chemotherapy and 26.3% for patients who had failed prior CD19 CAR -T (P=0.2098). CD79b antigen status was determined in 55/94 patients (58.5%), with 44/55 (80%) having antigen expression greater than 80%. The median follow-up time was 15.8 (range 8.8-18.3) months. In the salvage cohort, 6-month PFS and OS were 11.1% and 23.4%, respectively. In comparison, PFS and OS were significantly longer in the bridging cohort, resulting in 6-month PFS of 51.5%(P=0.0003) and OS of 61.3%(P=0.0008).In the bridging cohort, 6-month PFS (PFS 36.8% vs. 51.5%,P=0.2178)and OS (52.6% vs.61.3%,P=0.2176)were shorter in patients who had failed prior CD19 CAR -T cell therapy than in patients who had not been treated with CAR -T cell therapy.Although there was no statistical difference, the survival curves showed poor late survival in the group of patients in whom CAR -T had failed.(Figure 1).In each case, calculated from the start of Pola-based therapy.Significant factors for prolonged PFS on multivariate analysis were bridging CAR -T therapy (p< 0.0001), more cycles for Pola-based therapy (p =0.0001), and ORR achieved in the first two cycles (p=0.002). Summary/Conclusion: This study provides new insights into the timing of Pola-based salvage therapy in patients with refractory/relapsed B-cell lymphoma. In patients eligible for CAR -T cell therapy, early administration of Pola-based treatment as a bridge before CAR -T would significantly improve survival.Keywords: relapsed/refractory, CAR-T, B cell lymphoma, Salvage chemotherapy