CAR T-Cell Therapy Remain Effective in Patients with Relapse/Refractory B-Cell Non-Hodgkin Lymphoma after Bispecific Antibodies Exposure: Results of a Lysa Study Based on the Descar-T Registry

Abstract

Background Anti-CD19 Chimeric antigen receptor (CAR) T-cells and anti-CD3/CD20 bispecific antibodies (BA) have emerged as the most promising agents for the treatment of relapsed or refractory (R/R) B-cell lymphomas (B-NHL). Optimal sequencing of both treatment options is a matter of debate. Complete response around 30% have been reported with BA treatment of patients (pts) failing CAR T-cells. Given their promising efficacy and accessibility, BA may be given earlier in future therapeutic strategy, even before CAR T-cells. To date, there is no data regarding the outcome of pts treated with CAR T-cells after prior exposure to BA. Methods We retrospectively analyzed adult patients with R/R B-NHL treated with approved CAR T-cells (axi-cel, tisa-cel or brexu-cel) after prior exposure to BA. Patients’ data were collected through the French DESCAR-T registry and medical records. Results As of May 2nd 2022, we identified 32 pts in the DESCAR-T registry. Among those, 28 pts were evaluable for this analysis including 23 pts with large B-cell lymphoma (LBCL) (21 Diffuse large B-cell lymphoma, 1 Follicular lymphoma (FL) grade 3b and 1 High grade B-cell lymphoma), 3 Mantle cell lymphoma (MCL) and 2 FL. Patients had received a median of 4 (range: 2‒9) prior treatment lines before CAR-T cells therapy and 96.9% had refractory disease. Prior BA therapy were as follows: CD20/CD3 BA (n=26; 92.9% - mainly Glofitamab (n=18; 64.3%)), CD19/CD3 BA (n=1) and CD22/CD3 BA (n=1). BA were given as single agent for all pts but one who received a combination with lenalidomide. The best objective response rate (ORR) and complete response (CR) rates after BA were 53.6% and 25.0%, respectively. The median time to next treatment (TTNT) from BA initiation was 142 days (range : 37-482). In the LBCL subgroup, the 6-months (mo) PFS was 17.4% with a median PFS of 3.1 mo. In this subgroup, the median duration of response (DOR) was 2.7 mo. The reason for BA discontinuation was disease progression in all pts (missing information for 1 patient). The CAR T-cell type was axi-cel (n=16; 57.1%), tisa-cel (n=9; 32.1%) and brexu-cel (n=3; 10.7%). Twenty-three pts (82.1%) received bridging therapy. After CAR-T cell infusion, best ORR and CR rates were 92.9% and 50.0%, respectively. In the LBCL subgroup (Table 1), 72% received axi-cel and 28% received tisa-cel. Best ORR and CR rates after CAR T-cell infusion were 91.6% and 45.8%, respectively. After a median follow-up (FU) of 12.3 mo, the 1-year PFS (Figure 1) and OS were 37.2% and 53.5%, respectively. In this subgroup, the 1-year DOR was 40.7%. Among the 3 MCL and 2 FL, all pts responded and were progression free at the time of data cut-off. Cytokine release syndrome (CRS) occurred in 92.7% of pts, including 10.3% of grade 3 CRS (no grade 4). Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 32.3% of pts, including 3.6% of grade 3 ICANS (no grade 4). During the FU (median FU of 8.4 mo), 7 pts (25.0%) died: 3 from toxicity and 4 from lymphoma progression. Conclusion In this series, the efficacy of CART appears preserved in B-NHL patients whose disease progressed after prior treatment with bispecific antibodies. No new toxicity signals have been identified. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal