Lenalidomide plus rituximab for previously untreated advanced follicular lymphoma: the 10-year RELEVANCE trial analysis

N Nicolas Gower (1Service des Maladies du Sang, Centre Hospitalier Universitaire de Lille, Université de Lille, Lille, France) P Pierre Feugier (2Service Hématologie, Centre Hospitalier Régional Universitaire de Nancy–Hôpital Brabois, Université de Lorraine, Nancy, France) J Jason Westin (3Department of Lymphoma and Myeloma, MD Anderson Cancer Center, Houston, TX) J Jean-Marc Schiano De Colella (4Département Hématologie, Institut Paoli Calmettes, Marseille, France) H Hervé Tilly (5Service Hématologie, Centre Henri Becquerel, Rouen, France) M M. Lia Palomba (5Memorial Sloan Kettering Cancer Center, New York, NY) E Edith Julia G Gandhi-Laurent Damaj (8Institut d’Hématologie de Basse Normandie, Caen, France) A Amandine Durand (9Service Hématologie Clinique, Centre Hospitalier Universitaire Dijon Bourgogne, Dijon, France) I Ian Flinn (10OneOncology and Tennessee Oncology, Nashville, TN) F François Lemonnier (Princess Margaret Cancer Centre, University Health Network) N Nadine Morineau (12Service Hématologie, Centre Hospitalier Départemental Vendée, La Roche-sur-Yon, France) L Loic Ysebaert (13Service Hématologie, Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France) N Nancy Bartlett (14Department of Hematology and Oncology, Washington University School of Medicine Siteman Cancer Center Hematology Labs, St. Louis, MO) C Catherine Thieblemont (15Assistance Publique–Hôpitaux de Paris, Hôpital Saint-Louis, Hémato-Oncologie and Université Paris Cité, Paris, France) V Vincent Ribrag (16Département d’hématologie-Département d’Innovation Thérapeutique et des Essais Précoces, Gustave Roussy, Villejuif, France) T Thomas Gastinne A Arthur Dony (18Service Hématologie, Centre Hospitalier Metropole Savoie Chambéry, Chambéry, France) L Ludovic Fouillet (19Service Hématologie, Institut de Cancérologie et d’Hématologie Universitaire de Saint-Étienne, Saint-Priest-en-Jarez, France) S Stephanie Guidez (20Service d'Oncologie Hématologique et Thérapie Cellulaire, Centre Hospitalier Universitaire de Poitiers–Hôpital de la Miletrie, Poitiers, France) R Roch Houot (21Service d’Hématologie, Centre Hospitalier Universitaire Pontchaillou, Rennes, France) M Maria Gomes Da Silva (22Departamento Hematologia, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal) J Jeffrey Barnes (23Department of Hematology and Oncology, Harvard Medical School, Massachusetts General Hospital, Boston, MA) F Fontanet Bijou (24Service d'Hématologie, Institut Bergonie, Bordeaux, France) G Guillaume Cartron (CHU Montpellier UMR5535, Montpellier, France) A Alejandro Martin Garcia-Sancho H Herbert Eradat (27Department of Hematology and Oncology, Santa Monica Cancer Care, Santa Monica, CA) M Morgane Cheminant (28Service Hématologie Adultes, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique–Hôpitaux de Paris, Université Paris Cité, Paris, France) A Armando Lopez Guillermo (29Department of Hematology, Hospital Clinic Barcelona, Barcelona, Spain) P Pau Abrisqueta J Julie Abraham (31Service Hématologie Clinique et Thérapie Cellulaire, Centre Hospitalier Universitaire de Limoges–Hôpital Dupuytren, Limoges, France) C Clémentine Sarkozy (32Service Hématologie, Institut Curie–Site Saint-Cloud, Saint-Cloud, France) K Koji Izutsu (National Cancer Center Hospital, Tokyo, Japan) G Gilles Crochet (35Service Hématologie, Centre Hospitalier Universitaire UCL Namur–Site Godinne, Yvoir, Belgium) L Laurie H. Sehn (8Division of Medical Oncology, BC Cancer Centre for Lymphoid Cancer and The University of British Columbia, Vancouver, Canada) A Argyrios Gkasiamis (37Bristol Myers Squibb, Boudry, Switzerland) M Marie Laurence Yge (37Bristol Myers Squibb, Boudry, Switzerland) L Loic Chartier (38Biostatistics Department, Lymphoma Study Academic Research Organisation, Centre Hospitalier Lyon Sud, Pierre Benite Cedex, France) N Nathan Fowler (39Department of Hematology and Oncology, MD Anderson Cancer Center, Houston, TX) L Luc Xerri (40Aix Marseille Université, INSERM, Centre National de la Recherche Scientifique, Institut Paoli-Calmettes, Cancer Research Center of Marseille, Marseille, France) G Gilles Salles (41Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY) F Franck Morschhauser (Centre Hospitalier Universitaire de Lille, Groupe de Recherche sur les formes Injectables et les Technologies Associées, Lille, France)

Abstract

Abstract In the multinational, phase 3 RELEVANCE trial, 1030 patients with previously untreated follicular lymphoma were randomized to receive rituximab + lenalidomide (R2; n = 513) or rituximab-based immunochemotherapy (R-Chemo; n = 517). In the final analysis, at 120 months of follow-up, median progression-free survival (PFS) was comparable between the treatment groups: 110.6 months with R2 vs 102.8 months with R-Chemo, according to the independent review committee assessment. The 10-year PFS rates were 46.4% for R2 and 46.6% for R-chemo. Median overall survival (OS) and time-to-next lymphoma treatment (TTNLT) were not reached in either arm; 10-year OS rates were 82.4% for R2 and 81.1% for R-chemo, and 10-year TTNLT rates were 62.2% for R2 and 66.3% for R-chemo. Overall, patients with progression of disease within 24 months (POD24) had a poorer prognosis than those without POD24 (hazard ratio, 6.215; P< .0001); however, no difference was observed between the study groups. The incidence of second primary malignancies (SPMs) was 2.11 cases per 100 patient-years (95% confidence interval, 1.80-2.46). Only 9 transformations occurred after 24 months (3 with R2 vs 6 with R-chemo). In each study group, 87 patients died, mainly because of lymphoma progression and SPMs. This long-term follow-up of RELEVANCE confirmed that R2 provides a chemotherapy-free alternative to immunochemotherapy in this patient population. This trial was registered at www.clinicaltrials.gov as NCT01476787 and NCT01650701 and at EudraCT as 2011-002792-42.

Article Details

Journal Blood
Volume / Issue Vol. 147, Issue 25
Published June 18, 2026
Pages 3061-3068
ISSN 0006-4971
Publisher Elsevier BV

Journal Info

Blood

Elsevier BV

ISSN: 0006-4971 Health Sciences

Authors (42)

N

Nicolas Gower

1Service des Maladies du Sang, Centre Hospitalier Universitaire de Lille, Université de Lille, Lille, France

P

Pierre Feugier

2Service Hématologie, Centre Hospitalier Régional Universitaire de Nancy–Hôpital Brabois, Université de Lorraine, Nancy, France

J

Jason Westin

3Department of Lymphoma and Myeloma, MD Anderson Cancer Center, Houston, TX

J

Jean-Marc Schiano De Colella

4Département Hématologie, Institut Paoli Calmettes, Marseille, France

H

Hervé Tilly

5Service Hématologie, Centre Henri Becquerel, Rouen, France

M

M. Lia Palomba

5Memorial Sloan Kettering Cancer Center, New York, NY

E

Edith Julia

G

Gandhi-Laurent Damaj

8Institut d’Hématologie de Basse Normandie, Caen, France

A

Amandine Durand

9Service Hématologie Clinique, Centre Hospitalier Universitaire Dijon Bourgogne, Dijon, France

I

Ian Flinn

10OneOncology and Tennessee Oncology, Nashville, TN

F

François Lemonnier

Princess Margaret Cancer Centre, University Health Network

N

Nadine Morineau

12Service Hématologie, Centre Hospitalier Départemental Vendée, La Roche-sur-Yon, France

L

Loic Ysebaert

13Service Hématologie, Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France

N

Nancy Bartlett

14Department of Hematology and Oncology, Washington University School of Medicine Siteman Cancer Center Hematology Labs, St. Louis, MO

C

Catherine Thieblemont

15Assistance Publique–Hôpitaux de Paris, Hôpital Saint-Louis, Hémato-Oncologie and Université Paris Cité, Paris, France

V

Vincent Ribrag

16Département d’hématologie-Département d’Innovation Thérapeutique et des Essais Précoces, Gustave Roussy, Villejuif, France

T

Thomas Gastinne

A

Arthur Dony

18Service Hématologie, Centre Hospitalier Metropole Savoie Chambéry, Chambéry, France

L

Ludovic Fouillet

19Service Hématologie, Institut de Cancérologie et d’Hématologie Universitaire de Saint-Étienne, Saint-Priest-en-Jarez, France

S

Stephanie Guidez

20Service d'Oncologie Hématologique et Thérapie Cellulaire, Centre Hospitalier Universitaire de Poitiers–Hôpital de la Miletrie, Poitiers, France

R

Roch Houot

21Service d’Hématologie, Centre Hospitalier Universitaire Pontchaillou, Rennes, France

M

Maria Gomes Da Silva

22Departamento Hematologia, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal

J

Jeffrey Barnes

23Department of Hematology and Oncology, Harvard Medical School, Massachusetts General Hospital, Boston, MA

F

Fontanet Bijou

24Service d'Hématologie, Institut Bergonie, Bordeaux, France

G

Guillaume Cartron

CHU Montpellier UMR5535, Montpellier, France

A

Alejandro Martin Garcia-Sancho

H

Herbert Eradat

27Department of Hematology and Oncology, Santa Monica Cancer Care, Santa Monica, CA

M

Morgane Cheminant

28Service Hématologie Adultes, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique–Hôpitaux de Paris, Université Paris Cité, Paris, France

A

Armando Lopez Guillermo

29Department of Hematology, Hospital Clinic Barcelona, Barcelona, Spain

P

Pau Abrisqueta

J

Julie Abraham

31Service Hématologie Clinique et Thérapie Cellulaire, Centre Hospitalier Universitaire de Limoges–Hôpital Dupuytren, Limoges, France

C

Clémentine Sarkozy

32Service Hématologie, Institut Curie–Site Saint-Cloud, Saint-Cloud, France

K

Koji Izutsu

National Cancer Center Hospital, Tokyo, Japan

G

Gilles Crochet

35Service Hématologie, Centre Hospitalier Universitaire UCL Namur–Site Godinne, Yvoir, Belgium

L

Laurie H. Sehn

8Division of Medical Oncology, BC Cancer Centre for Lymphoid Cancer and The University of British Columbia, Vancouver, Canada

A

Argyrios Gkasiamis

37Bristol Myers Squibb, Boudry, Switzerland

M

Marie Laurence Yge

37Bristol Myers Squibb, Boudry, Switzerland

L

Loic Chartier

38Biostatistics Department, Lymphoma Study Academic Research Organisation, Centre Hospitalier Lyon Sud, Pierre Benite Cedex, France

N

Nathan Fowler

39Department of Hematology and Oncology, MD Anderson Cancer Center, Houston, TX

L

Luc Xerri

40Aix Marseille Université, INSERM, Centre National de la Recherche Scientifique, Institut Paoli-Calmettes, Cancer Research Center of Marseille, Marseille, France

G

Gilles Salles

41Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY

F

Franck Morschhauser

Centre Hospitalier Universitaire de Lille, Groupe de Recherche sur les formes Injectables et les Technologies Associées, Lille, France