Lenalidomide-rituximab or lenalidomide-rituximab-bendamustine for relapsed/refractory follicular lymphoma: primary and final analysis of the randomized phase II HOVON110/ReBeL study

The R2 (lenalidomide-rituximab) and R2 with bendamustine (R2B) regimens are both feasible in relapsed/refractory follicular lymphoma (R/R FL), but prospective phase II data on R2B are lacking. In this multinational, prospective, randomised, non-comparative trial, patients with R/R FL were randomised 1:1 to R2 (arm A) or R2B (arm B). Patients achieving CT-based partial or complete remission (PR/CR) received rituximab maintenance every 3 months for 2 years. Co-primary endpoints were investigator-assessed CR rates at end-of-induction (EOI) and severe toxicity rates. Between December 2014 and July 2019, 92 patients were randomized. The trial was stopped prematurely due to slow accrual. CR rates at EOI were 11.4% (95% CI [3.8, 24.6%]) for R2 and 15.2% (CI [6.3, 28.9%]) for R2B. With a median follow-up of 74 months, predefined severe toxicities occurred in 3 (6.8%; CI [1.4, 18.7%]) and 6 pts (13.0%, CI [4.9, 26.3%]) in Arm A and Arm B respectively, with 2 pneumonia-related deaths in arm A and no treatment-related deaths in arm B; 43% and 66% experienced any grade 3-4 AE (2%/7% grade 4). At 60 months, in arms A and B event free survival (EFS) was 39.5% (CI [25.1, 53.6%]) and 56.4% (CI [40.1, 69.3%]). Overall survival (OS) was excellent at 72.1% and 86.3%, respectively. R2 and R2B are both effective treatment regimens for R/R FL. While CT-based CR rates were low, treatment with R2B resulted in numerically longer median EFS and OS, but this was associated with higher toxicity.

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Journal
Haematologica
Published
2026-04-16
DOI
https://doi.org/10.3324/haematol.2025.300152
Primary Topic
Lymphoma Diagnosis and Treatment
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article
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article

Lenalidomide-rituximab or lenalidomide-rituximab-bendamustine for relapsed/refractory follicular lymphoma: primary and final analysis of the randomized phase II HOVON110/ReBeL study

J Dürig, Jeanette K. Doorduijn, Daphne de Jong, Martijn W. Heymans et al.
Haematologica
Lymphoma Diagnosis and Treatment
article

Lenalidomide-rituximab or lenalidomide-rituximab-bendamustine for relapsed/refractory follicular lymphoma: primary and final analysis of the randomized phase II HOVON110/ReBeL study

J Dürig, Jeanette K. Doorduijn, Daphne de Jong, Martijn W. Heymans, Matthijs Silbermann, Sanne H. Tonino, Cristina Mitea, Christel van Hooije, Sarah E. Coupland, A Beeker, Erik W.A. Marijt, Monique C. Minnema, Lidwine Winnifred Tick, Gabriele Prange‐Krex, Maria B. L. Leys, Marcel Kap, Lara H. Böhmer, Hein P. J. Visser, Roberto Liu, M Dreyling, Eva de Jongh, Anne I.J. Arens, Nelleke Tolboom, Axel Florschütz, M. L. H. Cuijpers, S Wiegers, Pamela McKay, Marie José Kersten, Kim M. Linton, Martine E.D. Chamuleau, Tjeerd Snijders, Rob Fijnheer, Andrew Pettitt, Wolfram Klapper, Josée M. Zijlstra, Yavuz M. Bilgin, Dana Chitu, Gerben J.C. Zwezerijnen
article en

Abstract

The R2 (lenalidomide-rituximab) and R2 with bendamustine (R2B) regimens are both feasible in relapsed/refractory follicular lymphoma (R/R FL), but prospective phase II data on R2B are lacking. In this multinational, prospective, randomised, non-comparative trial, patients with R/R FL were randomised 1:1 to R2 (arm A) or R2B (arm B). Patients achieving CT-based partial or complete remission (PR/CR) received rituximab maintenance every 3 months for 2 years. Co-primary endpoints were investigator-assessed CR rates at end-of-induction (EOI) and severe toxicity rates. Between December 2014 and July 2019, 92 patients were randomized. The trial was stopped prematurely due to slow accrual. CR rates at EOI were 11.4% (95% CI [3.8, 24.6%]) for R2 and 15.2% (CI [6.3, 28.9%]) for R2B. With a median follow-up of 74 months, predefined severe toxicities occurred in 3 (6.8%; CI [1.4, 18.7%]) and 6 pts (13.0%, CI [4.9, 26.3%]) in Arm A and Arm B respectively, with 2 pneumonia-related deaths in arm A and no treatment-related deaths in arm B; 43% and 66% experienced any grade 3-4 AE (2%/7% grade 4). At 60 months, in arms A and B event free survival (EFS) was 39.5% (CI [25.1, 53.6%]) and 56.4% (CI [40.1, 69.3%]). Overall survival (OS) was excellent at 72.1% and 86.3%, respectively. R2 and R2B are both effective treatment regimens for R/R FL. While CT-based CR rates were low, treatment with R2B resulted in numerically longer median EFS and OS, but this was associated with higher toxicity.

Haematologica
Radboud University Nijmegen (NL), University of Liverpool (GB), University of Applied Sciences Utrecht (NL), Utrecht University (NL), Leiden University Medical Center (NL), Maastricht University Medical Centre (NL), Beatson West of Scotland Cancer Centre (GB), Medisch Spectrum Twente (NL), Erasmus MC (NL), University Medical Center (US), Radboud University Medical Center (NL), Clatterbridge Cancer Centre NHS Foundation Trust (GB), University of Manchester (GB), University Medical Center Utrecht (NL), LMU Klinikum (DE), Hochschule für Angewandte Wissenschaften Kiel (DE), Christian-Albrechts-Universität zu Kiel (DE), Maastricht University (NL), Noordwest Ziekenhuisgroep (NL), Albert Schweitzer Ziekenhuis (NL), Städtisches Klinikum Dessau (DE), Spaarne Ziekenhuis (NL), Amsterdam Neuroscience (NL), Maasstad Ziekenhuis (NL), Essen University Hospital (DE), Máxima Medisch Centrum (NL), The Christie NHS Foundation Trust (GB), Haga Hospital (NL), Hovon (NL), Tergooi (NL), Admiraal De Ruyter Ziekenhuis (NL), Amsterdam University Medical Centers (NL), Rijnstate Hospital (NL), Meander Medisch Centrum (NL), Maastro Clinic (NL), Clinical Research Center Kiel (DE), University of Duisburg-Essen (DE), Technische Universität Dresden (DE), Ludwig-Maximilians-Universität München (DE), University of Amsterdam (NL), Erasmus University Rotterdam (NL)
Good health and well-being
Openalex Percentile: Top 22%
Lymphoma Diagnosis and Treatment
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