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

Clinical Lymphoma, Myeloma & Leukemia, 2025

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.

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Authors

Nastoupil LJ, Andersen CR, Ayers A, Wang Y, Habermann TM, Chihara D, Kahl BS, Link BK, Koff JL, Cohen JB, Martin P, Lossos IS, Stanchina M, Haddadi S, Casulo C, Ayyappan S, Lin R, Li Z, Larson MA, Maurer MJ, Huynh L, Gao C, Ramasubramanian R, Duh MS, Mutebi A, Wang T, Jun M, Wang A, Kamalakar R, Kalsekar A, Cerhan JR, Flowers CR