Pb2289: preliminary data from a first-in human phase ii study of sequential use of selinexor and cd19 chimeric antigen receptor modified t-cell therapy (cart19) in patients with relapsed or refractory b-cell non-hodgkin lymphoma

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Preclinical trial has demonstrated that sequential use of Selinexor and Anti-CD19 directed chimeric antigen receptor modified T-Cell therapy (CART19) cells might improve the anti‐tumor efficacy of CART 19 cells against lymphoma cells. However, the efficacy and safety of CART19 combined with Selinexor in lymphoma patients is unknown. We report preliminary data from a phase 2 trial of sequential use of Selinexor and CART19 in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (R/R B-NHL). Aims: This clinical study sequential use of Selinexor and CART19 was initiated with the aim of prolong relapse-free survival of CART19 cells therapy in R/R B-NHL patients. Methods: We performed a multicenter, prospective, phase II, open-label clinical study of sequential use of Selinexor and CART19 in R/R B-NHL. Patients received Selinexor as a bridging therapy (40-60mg) with a weekly for three weeks prior to CART19 infusion. Over all response (ORR), duration of response (DOR) and safety were evaluated as primary objectives. This study is registered with ClinicalTrials.gov, NCT05322330. Results: Between February 10, 2022, and February 10, 2023, 6 patients were enrolled. Four patients with diffuse large B-cell lymphoma, one mantle cell lymphoma and one Burkitt lymphoma received Selinexor 40mg and CART19 treatment. The median age was 55.5 years (range 34-77), 3 (50.0%) of 6 patients had refractory disease, 5 (83.3%) of 6 patients had extranodal involvement and the median prior systemic therapy was 2 (range 2-5), 5 (83.3%) of 6 patients had evaluated LDH prior to Selinexor administration. Median on-study follow-up was 9.68 months (range 2.53-12.17). 4 (66.7%) of 6 patients had an overall response. Cytokine release syndrome (CRS) was the most common adverse event, occurring in all 6 (100.0%) patients [66.7% was grade 1-2 and 33.3% was grade 3]. No neurotoxicity was observed. The most common grade 3-4 adverse events were neutropenia (5 [83.3%] of 6 patients), thrombocytopenia (4 [66.7%]), and anemia (3 [50.0%]). No treatment-related grade 5 adverse event occurred. Furthermore, our data showed that the use of Selinexor resulted in a higher proportion of CD8+central memory T cell phenotypes (P=0.04) while having no effect on CD4+ central memory T cell phenotypes (Figure 1). Summary/Conclusion: These results demonstrated that sequential use of Selinexor and CART19 in R/R B-NHL is effective and well tolerated in patients with R/R B-NHL. This study is ongoing and patients being recruited, more results should be evaluated in future.Figure 1. Selinexor significantly increased the proportion of CD8+ central memory T cells (CD3+CD8+CCR7+CD45RA-). Keywords: CAR-T, B cell lymphoma