Real-World Effectiveness of Chemoimmunotherapy and Novel Therapies for Patients With Relapsed/Refractory Aggressive Large B-Cell Lymphoma

This study examined the effectiveness of chemoimmunotherapy and novel therapies in patients (N = 866) with relapsed and/or refractory large B-cell lymphoma (r/r LBCL) treated in real-world practice settings. Patients derived limited clinical benefit from the treatments; those with high-risk disease, primary refractory status, and more prior lines of therapy had especially poor outcomes. More treatment options are needed for r/r LBCL. Introduction: Clinical trials provide meaningful data regarding the safety and efficacy of novel therapies but there is often a lag between the time of new drug approval and information on posttreatment clinical outcomes in real-world practice. This study evaluated clinical outcomes in a large real-world population of patients with relapsed and/or refractory large B-cell lymphoma (r/r LBCL) treated with chemoimmunotherapy or novel therapies in second or later lines of therapy (2L +). Materials and Methods: Data from the Lymphoma Epidemiology of Outcomes (LEO) Consortium of Real-World Evidence (CReWE) cohort (1/1/2015-2/15/2023) were analyzed. Patients' demographic and clinical characteristics were described and response rates, duration of response, progression-free survival, and overall survival were evaluated. Multivariable Cox proportional hazards regression models were used to assess associations between patient clinical characteristics and outcomes. Results: The 2L + cohort included patients treated with chemoimmunotherapy (N = 593), lenalidomide-based therapy (n = 60), polatuzumab vedotin-based therapy (N = 116), tafasitamab-based therapy (N = 55), and loncastuximab tesirine (N = 42). Most patients who received prior chimeric antigen receptor T-cell therapy (CAR-T) were refractory to the treatment. Across all patients, overall response rates were < 50%, with one-quarter achieving complete response and median duration of response and overall survival were short ( < 6 and < 10 months, respectively) among patients treated with chemoimmunotherapy or novel therapies. The prognosis was worse for patients who had previously received CAR-T. Primary refractory status, high-risk disease, and failing 3 or more lines of therapy were significantly associated with worse outcomes. Conclusion: Patients with r/r LBCL have unfavorable outcomes and need more effective treatment alternatives.