Lenalidomide plus R-GDP (R2-GDP) in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Final Results of the R2-GDP-GOTEL Trial and Immune Biomarker Subanalysis

Identifier:  imarina:9280994

Handle: https://hdl.handle.net/20.500.11797/imarina9280994

Authors:  Palazon-Carrion, Natalia; Martin Garcia-Sancho, Alejandro; Nogales-Fernandez, Esteban; Jimenez-Cortegana, Carlos; Carnicero-Gonzalez, Fernando; Rios-Herranz, Eduardo; de la Cruz-Vicente, Fatima; Rodriguez-Garcia, Guillermo; Fernandez-Alvarez, Ruben; Martinez-Banaclocha, Natividad; Guma-Padro, Josep; Gomez-Codina, Jose; Salar-Silvestre, Antonio; Rodriguez-Abreu, Delvys; Galvez-Carvajal, Laura; Labrador, Jorge; Guirado-Risueno, Maria; Garcia-Dominguez, Daniel J; Hontecillas-Prieto, Lourdes; Espejo-Garcia, Pablo; Fernandez-Roman, Isabel; Provencio-Pulla, Mariano; Sanchez-Beato, Margarita; Navarro, Marta; Marylene, Lejeune; Alvaro-Naranjo, Tomas; Casanova-Espinosa, Maria; Sanchez-Margalet, Victor; Rueda-Dominguez, Antonio; de la Cruz-Merino, Luis

Abstract:
New 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.©2022 The Authors; Published by the American Association for Cancer Research.