Comparative efficacy and safety of systemic therapies in transplant-eligible and ineligible relapsed/refractory large...

The advent of novel therapies including chimeric antigen receptor (CAR) T cells, bispecific antibodies (BsAbs), and antibody-drug conjugates (ADCs), has markedly improved clinical outcomes for relapsed or refractory large B-cell lymphoma (R/R LBCL). However, direct comparisons of efficacy and safety among systemic treatments for R/R LBCL are lacking, complicating clinical decision-making.

A systematic literature search was conducted across PubMed, Embase, and the Cochrane Library to identify eligible randomized controlled trials (RCTs). A Bayesian network meta-analysis (NMA) was performed to evaluate the systemic therapies across transplant-eligible and transplant-ineligible patients with R/R LBCL. The primary endpoint was progression-free survival (PFS), secondary endpoints included event-free survival (EFS), overall survival (OS), objective response rate (ORR) and grade ≥3 treatment-emergent adverse events (TEAEs).

The analysis included 14 RCTs comprising a total of 3,329 patients. Among the transplant-eligible cohort (7 evaluated regimens), CAR-T therapies maximized disease control; lisocabtagene maraleucel (liso-cel) ranked highest for PFS [hazard ratio (HR) =0.42; 95% credible intervals (CrI): 0.28-0.64] and EFS (HR =0.37, 95% CrI: 0.26-0.54), whereas axicabtagene ciloleucel (axi-cel) was associated with the highest incidence of grade ≥3 TEAEs [risk ratio (RR) =2.09; 95% CrI: 1.08-4.19]. In the transplant-ineligible cohort (9 evaluated regimens), glofitamab plus gemcitabine and oxaliplatin (Glofit-GemOx) ranked highest for PFS (HR =0.32; 95% CrI: 0.23-0.45), while polatuzumab vedotin plus bendamustine and rituximab (Pola-BR) yielded the maximum benefit for OS (HR =0.42; 95% CrI: 0.24-0.73) and ORR [odds ratio (OR) =5.21; 95% CrI: 2.01-14.3]. Both regimens were associated with higher toxicities, but remained overall manageable.

This NMA provides a comprehensive comparison of systemic treatment strategies for R/R LBCL regarding efficacy and safety profiles.