作者
Natalia Palazón‐Carrión,Alejandro Mart N Garc A-Sancho,Esteban Nogales-Fern Ndez,Carlos Jim Nez-Cortegana,Fernando Carnicero-Gonz Lez,Eduardo Ríos-Herranz,F Tima de la Cruz-Vicente,Guillermo Rodr Guez-Garc A,Rub N Fern Ndez-Lvarez,Natividad Martínez-Banaclocha,Josep Gumà,Jos G Mez-Codina,Antonio Salar-Silvestre,Delvys Rodr Guez-Abreu,Laura Gálvez,Jorge Labrador,Mar A Guirado-Risue O,Daniel J. García-Domínguez,Lourdes Hontecillas-Prieto,Pablo Espejo-Garc A,Isabel Fernández-Román,M. Provencio Pulla,Margarita Sánchez‐Beato,Marta Navarro,Marylène Lejeune,Tom S S Lvaro-Naranjo,María Casanova-Espinosa,Vı́ctor Sánchez-Margalet,Antonio Rueda-Dom Nguez,Luis de la Cruz‐Merino
摘要
Abstract Purpose: 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. Patients and Methods: 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). Results: 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. Conclusions: 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.