Contemporary Treatment Options Beyond Chimeric Antigen Receptor (CAR) T-Cell Therapies for Patients with Relapsed or Refractory Large B-Cell Lymphoma (LBCL): A Systematic Literature Review (SLR)

Background Refractory or relapsed large B-cell lymphoma (R/R LBCL) remains a significant challenge for patients (Coiffier et al. Blood. 2010). Chimeric antigen receptor (CAR) T-cell therapy has emerged as standard of care for most patients with R/R LBCL after receiving the initial line of treatment (Dreger et al. Blood Adv. 2020). Other therapies with different mechanisms of action also received regulatory approvals as second or third line (2L or 3L) treatment in recent years. We performed an SLR to understand the efficacy and real-world (RW) effectiveness of non–CAR T-cell therapies for R/R LBCL including tafasitamab with lenalidomide (tafa/len), polatuzumab with bendamustine/rituximab (pola-BR), loncastuximab, selinexor, epcoritamab, and glofitamab. Methods We systematically searched MEDLINE, EMBASE, and the Cochrane library for clinical trials or RW studies since 2017 that reported on ≥10 patients who had received the therapies of interest in 2L+ or 3L+. Hand searching of major conference databases was performed to identify additional abstracts. Outcomes of interest were objective response rate (ORR), complete response (CR) rate, progression-free survival, and overall survival (OS). These outcomes and key baseline characteristics were tabulated and summarized. Data from pivotal clinical trials and a recent SLR (Jacobson et al. Tandem Meeting. 2022) on commercially available CAR T-cell therapies were also included to provide context. Results One pivotal trial for each therapy of interest in 2L+ or 3L+ was identified. At 3L+, ORR ranged from 28% for selinexor to 63% for epcoritamab and glofitamab, and CR ranged from 12% for selinexor to 52% for glofitamab. Median OS ranged from 9.1 months for selinexor to 11.5 months for glofitamab and not reached for epcoritamab (Table). RW studies were also identified for tafa/len (2 for 2L+) and pola-BR (4 for 2L+; 3 for 3L+). Reported outcomes at 2L+ were numerically lower in RW studies (pola-BR, ORR 31%-57%, CR 19%-32%; tafa/len, ORR not reported, CR 9%) versus trials (pola-BR, ORR 63%, CR 53%; tafa/len, ORR 58%, CR 40%) (Table). Statistical analysis of the significance of the differences in baseline characteristics or outcomes between the therapies was not feasible. Conclusion Currently, the evidence base, particularly RW studies, for non–CAR T-cell R/R LBCL therapies is still limited. In comparison, 78 RW CAR T-cell therapy studies were published (Jacobson et al. Tandem Meeting. 2022) validating the efficacy findings from clinical trials. In general, the reported outcomes of non–CAR T-cell therapies—in clinical trials or RW studies—were numerically lower compared with their CAR T-cell therapy counterparts in both 2L+ and 3L+ except for epcoritamab and glofitamab versus tisagenlecleucel at 3L. Future studies should explore how best to sequence CAR T-cell and non–CAR T-cell therapies in the management of R/R LBCL for preferred outcomes.