Comparative effectiveness of salvage chemotherapy regimens and chimeric antigen T-cell receptor therapies in relapsed and refractory diffuse large B cell lymphoma: a network meta-analysis of clinical trials

The optimal salvage chemotherapy regimen (SC) for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) prior to autologous stem cell transplant remains unclear. Moreover, although chimeric antigen receptor T cell (CAR-T) therapies were recently approved for primary refractory DLBCL, head-to-head comparisons are lacking. We searched MEDLINE, EMBASE and CENTRAL to July 2022, for randomized trials that enrolled adult patients with R/R DLBCL and performed network meta-analyses (NMA) to assess the efficacy of SC and CAR-T therapies. NMA of SC (6 trials, 7 regimens, n = 1831) indicated that rituximab with gemcitabine, dexamethasone, cisplatin (R-GDP) improved OS and PFS over compared regimens. NMA of 3 CAR-T trials (n = 865) indicated that both axi-cel and liso-cel improved PFS over stand-of-care, with no difference in OS. Our results indicate that R-GDP may be preferred for R/R DLBCL over other SC compared. Longer follow-up is required for ongoing comparative survival analysis as data from CAR-T trials matures.

Automated summary

The optimal salvage chemotherapy regimen and the efficacy of chimeric antigen receptor T cell (CAR-T) therapies for relapsed/refractory diffuse large B-cell lymphoma (DLBCL) remain uncertain. A network meta-analysis showed that rituximab with gemcitabine, dexamethasone, cisplatin (R-GDP) improved overall survival (OS) and progression-free survival (PFS) compared to other salvage chemotherapy regimens. Another analysis of CAR-T trials demonstrated that both axi-cel and liso-cel improved PFS compared to standard-of-care, with no difference in OS. These findings suggest that R-GDP may be preferred for relapsed/refractory DLBCL, but longer follow-up and comparative survival analysis of CAR-T data are needed to confirm these results.