P1400: three years outcomes of primary mediastinal b cell lymphoma patients following anti cd19 car-t cell therapy - a single center experience

Topic: 25. Gene therapy, cellular immunotherapy and vaccination - Clinical Background: Primary mediastinal B- cell lymphoma (PMBCL), a pathobiologically unique subtype of aggressive B cell lymphoma, has excellent prognosis in front-line setting but dismal outcome as a relapse/refractory (r/r) disease. Chimeric antigen receptor (CAR) T cell therapy has shown great efficacy as a salvage therapy, though very few PMBCL patients were included in the pivotal trials. Data of longer follow-up is needed, as well as understanding the role of other immune therapies after CAR T-cell failure. Aims: To report the outcomes of point of care (POC) academic anti-CD19 CAR T cells and Axicabtagene ciloleucel (axi-cel) in R/R PMBCL patients. Methods: Data of all consecutive adults with R/R PMBCL treated with CAR T-cell therapy in Sheba Medical Center was collected. Inclusion criteria was >2 prior lines of treatment. Patients who received POC CAR-T cell therapy underwent peripheral blood leukapheresis. T-cells were activated and transduced with a gammaretrovirus encoding for a CD19 CAR (based on an FMC63-derived ScFv, a CD28 costimulatory domain, and a CD3-ζ signaling domain). Patients who received axi-cel (which also contains CD28 costimulatory domain) had their cells collected and sent for manufacturing abroad. Last follow up was 02/2023. Results: Twenty patients (POC, n=12 [60%]; axi-cel, n=8 [40%]) with a median age of 35 years, IQR 30-41) were included. The median time from leukapheresis to cell infusion was 10 (IQR 10-11) and 41 (IQR 38-41) days in patients who received POC CAR T and axi-cel, respectively. Eight patients (40%) received a bridging therapy. Five patients (20%) had Karnofsky performance status < 90%. Median previous lines of treatment were 2 (IQR 2-3). At enrollment, disease stage was III-IV in 9 (45%) patients; 6 patients (30%) had bulky disease; 12 patients (60%) had increased LDH and 12 patients (60%) had primary refractory disease. CAR-T cell therapy was well tolerated in most patients. Grade III-IV cytokine release and immune effector cell-associated neurotoxicity syndromes occurred in 3 (15%) and 5 (25%) patients, respectively. The cause of death was PD in 10 patients (50%), and 1 (5%) patient died of unrelated cause while in complete response (CR). Response was evaluated in all patients at 1-month. Overall response rate was 75% (35% CR). Among the 8 patients who achieved a PR at 1 month, 5 achieved a subsequent CR; (2/5 spontaneously, 2/5 after consolidation with radiation and 1 patient after allogeneic transplantation). The median follow up was 32.6 months (IQR 27.7 -42.9). One year and 3-year overall survival were 69% (95% CI, 52-93) and 41% (95% CI, 24-71) respectively. One year, and 3-year progression-free survival were 40% (95% CI, 23-68) and 33% (95%CI, 17-64) respectively (Figure 1). The median duration of response (DOR) was 26.4 months (95%CI 1.9-not reached) After relapse/progression following CAR-T, 5 patients (30%) received pembrolizumab, 2 of those patients achieved a sustained CR and have not progressed for over 2 years of follow-up. Five of six patients who underwent allogeneic transplantation following CAR- T due to progression died within 1 year of transplantation. Summary/Conclusion: Anti-CD19 CAR T-cell therapy induced a high ORR and an encouraging DOR in patients with r/r PMBCL. The role of radiation after CAR-T cell needs further evaluation in prospective studies. Pembrolizumab might be a promising salvage in patients with PMBCL after CAR T-cell failure. Figure 1. overall survival (A) and progression-free survival (B) of PMBCL patients since CAR-TKeywords: High-grade non-Hodgkins-lymphoma, CAR-T, Immune therapy, Point-of-care