OBJECTIVES: To assess the efficacy and safety of approved CAR-T therapies used in the treatment of relapsed and refractory DLBCL patients

METHODS: We searched Medline, Cochrane, ClinicalTrials.gov databases for the identification of clinical trials comparing approved CAR-T therapies including Kymriah, Yescarta, and Breyanzi. The search strategy consisted of CAR-T interventions and DLBCL terms. The primary outcomes of interest were overall response rate (ORR), overall survival rate, Progression free survival (PFS), and adverse events including CRS (Cytokine Release Syndrome). Two reviewers independently conducted the screening, data abstraction, and the quality assessment. The included studies were critically appraised using MINORS checklist. Meta-analysis was conducted using meta package in R software.

RESULTS: A total of 80 clinical trials were included for the data extraction. All randomized, non-randomized, and single arm studies were included. Most of the studies were single arm so the meta-analysis was conducted on individual treatment arms using metaprop. The pooled estimates showed that ORR was comparatively higher in Breyanzi group (73%, 95% CI: 69%-77%) followed by Yescarta (59%, 95% CI: 57%-61%) and Kymriah (50%, 95% CI: 43%-56%). Overall survival rate was better in Kymriah group (79%, 95% CI: 77%-81%) in comparison to Yescarta (73%, 95% CI: 69%-76%), however Yescarta showed higher PFS than Kymriah. All treatments were equally tolerable however reported some serious adverse events. The most commonly observed adverse events were CRS, neurotoxicity, encephalopathy, and neurological events. Yescarta reported a relatively high CRS rate compared to Kymriah (44% vs. 19% respectively). Patients receiving Kymriah had a higher rate of neurotoxicity and Yescarta showed higher encephalopathy rate.

CONCLUSIONS: Our findings demonstrated that the CAR-T therapies are equally efficacious and comparatively safer, however some serious adverse events were also reported. Though Yescarta showed relatively improved efficacy profile though all three treatments were better compared to other standards of care (SOC).