Palazón-Carrión, NataliaMartín García-Sancho, AlejandroNogales-Fernández, EstebanJiménez-Cortegana, CarlosCarnicero-González, FernandoRíos-Herranz, Eduardode la Cruz-Vicente, FátimaRodríguez-García, GuillermoFernández-Álvarez, RubénMartínez-Banaclocha, NatividadGumà-Padrò, JosepGómez-Codina, JoséSalar-Silvestre, AntonioRodríguez-Abreu, DelvysGálvez-Carvajal, LauraLabrador, JorgeGuirado-Risueño, MaríaGarcía-Domínguez, Daniel JHontecillas-Prieto, LourdesEspejo-García, PabloFernández-Román, IsabelProvencio-Pulla, MarianoSánchez-Beato, MargaritaNavarro, MartaMarylene, LejeuneÁlvaro-Naranjo, TomásCasanova-Espinosa, MariaSánchez-Margalet, VictorRueda-Domínguez, Antoniode la Cruz-Merino, Luis2023-05-032023-05-032022http://hdl.handle.net/10668/20187New therapeutic options are needed in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Lenalidomide-based schedules can reverse rituximab refractoriness in lymphoma. In the phase II R2-GDP trial, 78 patients unsuitable for autologous stem cell transplant received treatment with the following schedule: lenalidomide 10 mg Days (D)1-14, rituximab 375 mg/m2 D1, cisplatin 60 mg/m2 D1, gemcitabine 750 mg/m2 D1 and D8, and dexamethasone 20 mg D1-3, up to 6 cycles (induction phase), followed by lenalidomide 10 mg (or last lenalidomide dose received) D1-21 every 28 days (maintenance phase). Primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and monitorization of key circulating immune biomarkers (EU Clinical Trials Register number: EudraCT 2014-001620-29). After a median follow-up of 37 months, ORR was 60.2% [37.1% complete responses (CR) and 23.1% partial responses (PR)]. Median OS was 12 months (47 vs. 6 months in CR vs. no CR); median PFS was 9 months (34 vs. 5 months in CR vs. no CR). In the primary refractory population, ORR was 45.5% (21.2% CR and 24.3% PR). Most common grade 3-4 adverse events were thrombocytopenia (60.2%), neutropenia (60.2%), anemia (26.9%), infections (15.3%), and febrile neutropenia (14.1%). Complete responses were associated with a sharp decrease in circulating myeloid-derived suppressor cells and regulatory T cells. R2-GDP schedule is feasible and highly active in R/R DLBCL, including the primary refractory population. Immune biomarkers showed differences in responders versus progressors.enAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/Antineoplastic Combined Chemotherapy ProtocolsBiomarkersHumansLenalidomideLymphoma, Large B-Cell, DiffuseLymphoma, Non-HodgkinNeoplasm Recurrence, LocalRituximabTreatment Outcomeresearch article35727601open access10.1158/1078-0432.CCR-22-05881557-3265PMC9433956https://aacrjournals.org/clincancerres/article-pdf/28/17/3658/3199480/3658.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9433956/pdf