OBJECTIVES: Relapsed or refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL) patients undergo multiple lines of burdensome therapies. We conducted a network meta-analysis (NMA) of phase 3 randomized control trials (RCTs) to evaluate the effectiveness of second-line (2L) immune targeted treatments (ITTs), including Chimeric Antigen Receptor (CAR)-T cell therapies in r/r DLBCL patients, focusing on overall survival (OS) and event-free survival (EFS).

METHODS: In a systematic review, we searched RCTs from PubMed, Embase and Cochrane library spanning January 2016 to September 2023. We included studies reporting on adults (≥18 years) DLBCL patients experiencing R/R to first-line anti-CD20 antibody and anthracycline-containing regimen. RCTs comparing ITTs with SOC (2L salvage chemoimmunotherapy regimens followed by stem cell transplantation) were included. Frequentist fixed-effect model was utilized to estimate hazard ratios (HRs) with corresponding 95% confidence intervals (CIs). We ranked treatment effectiveness based on the surface under the cumulative ranking curves (SUCRA).

RESULTS: Our search identified 539 records; four RCTs contributed to the NMA: three comparing CAR-Ts, axicabtagene ciloleucel (axi-cel), lisocabtagene maraleucel (liso-cel), tisagenlecleucel (tisa-cel) with SOC, and one comparing ofatumumab + cisplatin, cytarabine, dexamethasone (O-DHAP) with SOC. Axi-cel significantly improved OS compared to both tisa-cel (HR, 0.59; 95% CI, 0.36-0.96) and SOC (HR, 0.73; 95% CI, 0.55-0.98). However, no significant differences in OS were observed for other ITTs versus SOC. For EFS, axi-cel (HR, 0.38; 95% CI, 0.27-0.53) and liso-cel (HR, 0.32; 95% CI, 0.21-0.51) showed significant improvement compared to ODHAP. Axi-cel and liso-cel improved EFS significantly when individually compared to tisa-cel, and SOC. In the SUCRA rankings, axi-cel was the most effective for OS, liso-cel ranked the most effective for EFS.

CONCLUSIONS: Axi-cel was consistently associated with improved OS and EFS when compared to tisa-cel and SOC while liso-cel improved EFS over Tisa-cel, ODHAP and SOC. Results are constrained by lack of multiple studies for each treatment comparison.