Meta-Analysis of CAR-T Therapy vs SOC for 2L Treatment of Patients with R/R LBCL

High-dose chemotherapy (HDCT) followed by autologous stem-cell transplantation (ASCT) is considered the standard-of-care (SOC) treatment for relapsed or refractory (R/R) large B-cell lymphoma (LBCL) in the second-line (2L) setting in patients responding to salvage therapy; however, >50% of patients will not proceed to ASCT due to progressive disease. CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy is now considered as the SOC for patients with R/R LBCL after ≥2 lines of therapy. Randomized, prospective studies have recently examined whether earlier utilization of CAR-T therapy could improve outcomes; thus, findings from a meta-analysis comparing the efficacy and safety of CAR-T versus HDCT followed by ASCT as 2L treatment for R/R LBCL were presented at the 2022 European Hematology Association Congress.

A systematic review and meta-analysis of randomized controlled trials including pertinent patients with R/R LBCL comparing 2L treatment with HDCT followed by ASCT to CAR-T therapy was conducted utilizing Cochrane Library, PubMed, conference proceedings, and references from 2017 until January 2022; 2 reviewers validated the quality of trials and extracted data. The primary outcome was overall survival (OS). Secondary outcomes included overall response rate (ORR), complete response (CR) rate, event-free survival (EFS), progression-free survival (PFS), and safety.

The search yielded 3 trials (1 abstract, and 2 published in peer-reviewed journals) between 2018 and 2021, including 865 patients overall. The age of patients enrolled ranged from 19 to 81 years, with each trial testing 1 of the 3 FDA-approved CD19-directed CAR-T therapies: axicabtagene ciloleucel (ZUMA-7 study [NCT03391466]), tisagenlecleucel (BELINDA study [NCT03570892]), and lisocabtagene maraleucel (TRANSFORM study [NCT03575351]). All trials included patients with LBCL who were either refractory to frontline therapy or relapsed at ≤12 months (mo); median follow-up ranged between 6 and 24 mo among the trials. Data for OS, ORR, CR rate, and EFS were available for all 3 trials; however, data for PFS were only available for 2 trials. OS was significantly improved with CAR-T compared to SOC (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.60-0.98). CAR-T was also associated with significantly better ORR (relative risk [RR], 1.55; 95% CI, 1.12-2.13), CR rate (RR, 1.49; 95% CI, 1.09-2.05), and EFS (HR, 0.57; 95% CI, 0.49-0.68) compared to SOC. Available data for PFS (2 of 3 trials; N = 543) revealed significant improvements with CAR-T compared to SOC (HR, 0.47; 95% CI, 0.37-0.60). Regarding safety, all 3 trials reported grade 3-4 adverse events (AEs); the risk of grade 3-4 AEs was comparable between the 2 arms (RR, 1.03; 95% CI, 0.93-1.14).

This systematic review and meta-analysis concluded that CAR-T therapy has superior outcomes compared to the historic SOC in LBCL refractory to frontline therapy or relapsing at ≤12 mo, without excess toxicity. CAR-T therapy was associated with significantly improved ORR and CR rates, in addition to longer EFS and PFS, which translated into improved OS. However, longer follow-up is needed to confirm these results and determine the optimal sequencing of CAR-T therapy in the management of R/R LBCL.

Source

Shargian L, Raanani P, Yeshurun M, et al. CAR-T vs. standard of care as second line treatment for large B-cell lymphoma: a systematic review and meta-analysis. Presented at: 2022 European Hematology Association Congress, June 9-17, 2022; Vienna, AT. Abstract 1461.