Renoir phase III Rituximab-Lenalidomide vs Rituximab as Maintenance Treatment in Relapsed/Refractory Follicular Lymphoma

Maintenance treatment in elderly patients with relapsed or refractory (R/R) follicular lymphoma (FL) remains an area of investigation. RENOIR was a multicenter, phase III, open-label randomized trial conducted by the Fondazione Italiana Linfomi (FIL) in elderly patients with R/R FL after one or two prior therapies. Patients achieving partial or complete response (PR/CR) after 4-6 cycles of standard rituximab-based chemotherapy were randomized 1:1 to maintenance with rituximab alone (R, standard arm) or rituximab plus lenalidomide (R2, experimental arm). The primary endpoint was 2-year progression-free survival (PFS) from randomization with an expected HR =0.5. A total of 152 patients (median age 71 years) were enrolled. After induction, 129 (85%) achieved an overall response (CR 58%) and were randomized to R (n=65) or R2 (n=64). At a median follow-up of 68 months, the 2-year PFS was 73% in the R2 arm and 64% in the R arm (HR 0.73, 95% CI 0.46-1.16, p=.183). An unplanned hypothesis- generating subgroup analysis showed a greater 2-year PFS benefit with R2 in patients aged <70y (HR=0.35): R2 96% vs R 69%. Two-year overall survival (OS) rates were similar (R2 80% vs R 89%; HR 1.12). Grade 3/4 adverse events were more frequent in R2, mainly neutropenia and gastrointestinal disorders. In conclusion, the primary endpoint of the study was not met and R2 maintenance did not significantly improve 2-year PFS in elderly patients with R/R FL, though a numerically benefit was observed. R2 showed a more favorable benefit/risk profile in patients <70 years whereas in older patients careful consideration of individual tolerability is warranted. Trial registration: RENOIR study (NCT02390869) clinicaltrial.gov.

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Journal
Blood Advances
Published
2026-06-25
DOI
https://doi.org/10.1182/bloodadvances.2025018732
Primary Topic
Lymphoma Diagnosis and Treatment
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article

Renoir phase III Rituximab-Lenalidomide vs Rituximab as Maintenance Treatment in Relapsed/Refractory Follicular Lymphoma

Umberto Vitolo, Simone Ferrero, Stefano Luminari, Monica Tani et al.
Blood Advances
Lymphoma Diagnosis and Treatment
article

Renoir phase III Rituximab-Lenalidomide vs Rituximab as Maintenance Treatment in Relapsed/Refractory Follicular Lymphoma

Umberto Vitolo, Simone Ferrero, Stefano Luminari, Monica Tani, Donato Mannina, Alessia Bari, Vittorio Ruggero Zilioli, Carola Boccomini, Andrea Evangelista, Annarita Conconi, Annalisa Chiarenza, Gianluca Gaïdano, Delia Rota‐Scalabrini, Benedetta Puccini, Giovannino Ciccone, Elisa Genuardi, Nilla Maschio, Barbara Botto, Chiara Bottelli, Francesco Merli, Fabrizio Ciambelli, Piero Galieni, Anna Marina Liberati, Manuela Zanni, Erika Meli, Gerardo Musuraca, Cristina Muzi, Claudia Castellino, Annalisa Arcari, Sara Bigliardi, Giorgia Matta, Benedetta Bianchi, Chiara Rusconi, Federica Cavallo, Antonella Anastasia, Ilaria Del Giudice, Michele Spina, Marco Ladetto, Dario Marino
article en

Abstract

Maintenance treatment in elderly patients with relapsed or refractory (R/R) follicular lymphoma (FL) remains an area of investigation. RENOIR was a multicenter, phase III, open-label randomized trial conducted by the Fondazione Italiana Linfomi (FIL) in elderly patients with R/R FL after one or two prior therapies. Patients achieving partial or complete response (PR/CR) after 4-6 cycles of standard rituximab-based chemotherapy were randomized 1:1 to maintenance with rituximab alone (R, standard arm) or rituximab plus lenalidomide (R2, experimental arm). The primary endpoint was 2-year progression-free survival (PFS) from randomization with an expected HR =0.5. A total of 152 patients (median age 71 years) were enrolled. After induction, 129 (85%) achieved an overall response (CR 58%) and were randomized to R (n=65) or R2 (n=64). At a median follow-up of 68 months, the 2-year PFS was 73% in the R2 arm and 64% in the R arm (HR 0.73, 95% CI 0.46-1.16, p=.183). An unplanned hypothesis- generating subgroup analysis showed a greater 2-year PFS benefit with R2 in patients aged <70y (HR=0.35): R2 96% vs R 69%. Two-year overall survival (OS) rates were similar (R2 80% vs R 89%; HR 1.12). Grade 3/4 adverse events were more frequent in R2, mainly neutropenia and gastrointestinal disorders. In conclusion, the primary endpoint of the study was not met and R2 maintenance did not significantly improve 2-year PFS in elderly patients with R/R FL, though a numerically benefit was observed. R2 showed a more favorable benefit/risk profile in patients <70 years whereas in older patients careful consideration of individual tolerability is warranted. Trial registration: RENOIR study (NCT02390869) clinicaltrial.gov.

Blood Advances
University of Modena and Reggio Emilia (IT), Università degli Studi del Piemonte Orientale “Amedeo Avogadro” (IT), Policlinico Umberto I (IT), Ospedale di Circolo e Fondazione Macchi (IT), Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT), Ospedale Maggiore (IT), Azienda Sanitaria Unità Locale di Reggio Emilia (IT), Ospedale degli Infermi (IT), Ospedale "Santa Maria delle Croci" di Ravenna (IT), Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (IT), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IT), Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT), Azienda Ospedaliero-Universitaria di Modena (IT), Istituto Oncologico Veneto (IT), Ospedale Civile Di Ivrea (IT), Azienda Ospedaliero-Universitaria Careggi (IT), Azienda Ospedaliera S.Maria (IT), Ospedale di Circolo di Busto Arsizio (IT), Centro di Riferimento Oncologico (IT), Policlinico Universitario di Catania (IT), Ospedale Castelfranco Veneto (IT), Azienda Sanitaria Ospedaliera S.Croce e Carle Cuneo (IT), Guglielmo da Saliceto Hospital (IT), Fondazione Audiologica Varese (IT), Candiolo Cancer Institute (IT), Ospedale degli Infermi (IT), Ospedale di Prato Santo Stefano (IT), Fondazione IRCCS Istituto Nazionale dei Tumori (IT), Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare Arrigo (IT), Azienda Ospedaliero Universitaria Policlinico "G.Rodolico - San Marco" (IT), Azienda Ospedaliera Ospedali Riuniti Papardo Piemonte (IT), Fondazione Piemontese per la Ricerca sul Cancro Onlus (IT)
Good health and well-being
Openalex Percentile: Top 8%
Lymphoma Diagnosis and Treatment
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