Real-World Efficacy and Safety of the Combination of Rituximab, Lenalidomide, and Ibrutinib in Patients with Relapsed and/or Refractory Non-Hodgkin Lymphoma.

Relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) is associated with poor outcomes, and the therapeutic options are limited. In some clinical studies, rituximab, lenalidomide, and ibrutinib (RLI) have shown promising efficacy. Consequently, we evaluated RLI in a real-life setting. This retrospective, single-center study analyzed the outcomes of RLI as an off-label salvage therapy in patients with R/R NHL from June 2020 to 2024. We analyzed twenty-four patients, including diffuse large B-cell lymphoma (DLBCL) ( = 18), primary central nervous system lymphoma (PCNSL) ( = 2), mantle cell lymphoma (MCL) ( = 2), and marginal zone lymphoma (MZL) ( = 2). The most common adverse events (AEs) were fatigue (42%), neutropenia (42%), and infection (33%). The median time to response (TTR) was two months (1.7-3.8). The overall response rate (ORR) was 46% (95% CI 24%-67%), with 33% complete response (CR) and 13% partial response (PR). The median duration of response (DoR) was 31 months (range, 0.6-46+). The median overall survival (OS) was eight months (95% CI 2.2-13.7 months), and the median progression-free survival (PFS) was 6.3 months (95% CI 0.0-25.1 months). Our results suggest that RLI is a viable therapeutic option with promising activity and a favorable toxicity profile in patients with R/R NHL.