Unmet Needs and Evidence Gaps Among Patients with DLBCL treated with CAR-T Therapy: A Systematic Literature Review

OBJECTIVES: This study aimed to review current literature on the real-world (RW) efficacy, safety, healthcare resource use (HRU), and costs of innovative treatments for diffuse large B-cell lymphoma (DLBCL).
METHODS: A systematic literature review (SLR) was conducted (1/1/2017-4/9/2024) to identify RW studies on the use of innovative treatments for DLBCL treatment among adults in the United States.
RESULTS: Of the 1,256 records identified, 92 RW studies were selected for inclusion. Among patients receiving chimeric antigen receptor T-cell (CAR-T), the most commonly reported bridging therapies included chemotherapy, radiotherapy, and corticosteroids. However, no preferred option or clear guidance on these therapies emerged. Complete response rates were generally higher for axicabtagene ciloleucel (40-58%) than tisagenlecleucel (25-38%) or lisocabtagene maraleucel (15%). Respectively 5 and 3 studies reported on overall survival (OS) and progression free survival (PFS) for axicabtagene ciloleucel, with median OS ranging from 16.4-25.5 months and median PFS ranging from 4.5-8.9 months. Cytokine release syndrome was commonly reported for CAR-T (N=32 studies; grade 3+: 0-32%), along with immune effector cell-associated neurotoxicity syndrome (N=20 studies; grade 3+: 0-39%). Patients who received CAR-T in the outpatient vs. inpatient setting had lower use of inpatient and intensive care unit services post-infusion. Total costs for CAR-T therapies were generally higher than other innovative treatments. No studies formally compared adverse events, HRU, and costs across CAR-T therapies using covariate-adjusted analyses. Several different treatments were used after CAR-T among patients with CAR-T failure, but outcomes were generally poor.
CONCLUSIONS: In this SLR, formal comparisons across CAR-T therapies and in different settings (i.e., inpatient vs. outpatient) in DLBCL are scarce. More research is needed to identify the most appropriate bridging therapy and treatments post-CAR-T failure to optimize outcomes for patients with different clinical profiles. Additional RW evidence is also needed to better understand how CAR-T administration can be further optimized to improve patient outcomes.