Anti-CD19 chimeric antigenic receptor T cell as a second-line therapy for patients with relapsed/refractory diffuse large B-cell lymphoma.

Abstract

e19502 Background: Inconsistent results observed in recent trials (ZUMA-7, TRANSFORM, BELINDA) assessing chimeric antigenic receptor T (CAR-T) cell therapy in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) prompted a meta-analysis to assess the available evidence and to compare the effectiveness of different CAR-T products. Methods: MEDLINE and EMBASE were searched to identify full-text or abstract publications of phase 3 randomized controlled trials (RCTs) assessing CAR-T in patients with R/R DLBCL compared to standard of care (SOC). Efficacy outcomes included event-free survival (EFS), progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and complete response (CR). CR rates were also compared between CAR-T and patients in SOC arm who received autologous stem-cell transplantation (ASCT). Safety outcomes included grade > 3 any adverse events (AE), cytokine release syndrome (CRS) and neurological toxicity (NT). A DerSimonian-Laird random-effects meta-analysis was conducted to pool effect estimates. Freeman-Tukey transformation method was used to estimate pooled proportion (PP) of safety events specific to CAR-T. Mixed treatment comparisons were computed using a frequentist network meta-analysis approach. Results: Of 1803 studies identified, three RCTs with 865 patients were included. Meta-analysis showed significant improvement in EFS (HR: 0.51; 95% CI: 0.27-0.97; I2: 92%), PFS (HR: 0.47; 95% CI: 0.37-0.60; I2: 0%) with CAR-T compared to SOC. OS was not significantly different between the two groups (HR 0.76; 95% CI: 0.56 to 1.03; I2: 29%). Higher objective response (RR: 1.49; 95% CI: 1.13-1.97; I2: 81%), and CR rates (RR: 1.55; 95% CI: 1.07-2.24; I2: 79%) were observed with CAR-T compared to SOC. However, CAR-T was associated with lower CR when compared to patients who underwent ASCT (RR: 0.65; 95% CI: 0.46-0.90; I2: 89%). The safety profile was not different between CAR-T and SOC. The incidences of grade ≥3 CRS (PP: 4.19; 95% CI: 1.60-7.80; I2: 57%) and grade ≥3 NT (PP: 7.57; 95% CI: 0.20-22.6; I2: 95%) were low. Mixed treatment comparisons showed significant EFS benefit with liso-cel (rank 1: HR: 0.37; 95% CI: 0.22-0.61) and axi-cel (rank 2: HR: 0.42; 95% CI: 0.29-0.61) compared to tisa-cel (rank 3). No significant differences were observed among different CAR-T products for PFS or OS improvement. The safety profile of CAR-T products was comparable with tisa-cel (rank 1) being the safest. Conclusions: CAR-T therapy, as a second line treatment, appears to be effective in achieving higher response rates and delaying the disease progression compared to SOC in R/R DLBCL. However, given lack of OS benefit coupled with lower response rates when compared to patients who received ASCT, we should exercise caution in adopting CAR-T as second line therapy for all patients with R/R DLBCL.