Lenalidomide with or without erythropoietin in transfusion-dependent erythropoiesis-stimulating agent-refractory lower-risk MDS without 5q deletion.
After failure of erythropoiesis-stimulating agents (ESAs), lenalidomide (LEN) yields red blood cell (RBC) transfusion independence (TI) in 20-30% of lower-risk non-del5q myelodysplastic syndrome (MDS). Several observations suggest an additive effect of ESA and LEN in this situation. We performed a randomized phase III study in 131 RBC transfusion-dependent (TD, median transfusion requirement six RBC units per 8 weeks) lower-risk ESA-refractory non-del5q MDS. Patients received LEN alone, 10 mg per day, 21 days per 4 weeks (L arm) or LEN (same schedule) + erythropoietin (EPO) beta, 60,000 U per week (LE arm). In an intent-to-treat (ITT) analysis, erythroid response (HI-E, IWG 2006 criteria) after four treatment cycles (primary end point) was 23.1% (95% CI 13.5-35.2) in the L arm and 39.4% (95% CI 27.6-52.2) in the LE arm (P=0.044), while RBC-TI was reached in 13.8 and 24.2% of the patients in the L and LE arms, respectively (P=0.13). Median response duration was 18.1 and 15.1 months in the L and LE arms, respectively (P=0.47). Side effects were moderate and similar in the two arms. Low baseline serum EPO level and a G polymorphism of CRBN gene predicted HI-E. Combining LEN and EPO significantly improves erythroid response over LEN alone in lower-risk non-del5q MDS patients with anemia resistant to ESA.
Department of Hematology, Hopital Universitaire Henri Mondor, Assistance Publique-Hôpitaux de Paris (APHP) and Paris 12 University, Creteil, France.
A
A
Toma
Assistance Publique-Hopitaux de Paris, Hopital Cochin, Laboratory of Hematology and Paris Descartes University, Paris, France.
O
O
Kosmider
Biostatistics Team (ECSTRA), UMR1153, Inserm, Hopital Saint Louis, APHP and Paris 7 University, Paris, France.
S
S
Chevret
Department of Hematology, Centre Hospitalier Universitaire, Nantes, France.
J
J
Delaunay
Department of Hematology, Centre Henri Becquerel, Rouen, France.
A
A
Stamatoullas
Department of Hematology, Hopital Saint Vincent de Paul, Lomme, France.
C
C
Rose
Department of Hematology, Centre Hospitalier Universitaire, Purpan, France.
O
O
Beyne-Rauzy
Department of Hematology, Centre Hospitalier Universitaire, Strasbourg, France.
A
A
Banos
Department of Hematology, Centre Hospitalier Universitaire, Nancy, France.
A
A
Guerci-Bresler
Department of Hematology, Centre Hospitalier Universitaire, Nimes, France.
S
S
Wickenhauser
Department of Hematology, Centre Hospitalier Universitaire, Dijon, France.
D
D
Caillot
Department of Hematology, Centre Hospitalier, Le Mans, France.
K
K
Laribi
Department of Hematology, Centre Hospitalier Universitaire, Clermont Ferrand, France.
B
B
De Renzis
Department of Hematology, Centre Hospitalier Universitaire, Limoges, France.
D
D
Bordessoule
Department of Hematology, Hopital Avicenne, APHP, and Paris 13 University Bobigny, Bobigny, France.
C
C
Gardin
Department of Hematology, Centre Hospitalier, Avignon, France.
B
B
Slama
Department of Hematology, Centre Hospitalier, Perpignan, France.
L
L
Sanhes
Department of Hematology, Hopital Universitaire Amiens, Amiens, France.
B
B
Gruson
Department of Hematology, Centre Hospitalier Annecy-Genevois, Prigny, France.
P
P
Cony-Makhoul
Department of Hematology, Centre Hospitalier, Boulogne sur Mer, France.
B
B
Chouffi
Department of Hematology, Centre Hospitalier, Corbeil, France.
C
C
Salanoubat
Department of Hematology, Centre Hospitalier, Pontoise, France.
R
R
Benramdane
Department of Hematology, Centre Hospitalier Universitaire, Nice, France.
L
L
Legros
Department of Hematology, Centre Hospitalier Edouard Herriot, Lyon, France.
E
E
Wattel
Department of Hematology, Hopital Kremlin Bicetre, APHP, Kremlin Bicetre, France.
G
G
Tertian
Department of Hematology, Centre Hospitalier Universitaire, Bordeaux, France.
K
K
Bouabdallah
Department of Hematology, Centre Hospitalier Jean Bernard, Poitiers, France.
F
F
Guilhot
Department of Hematology, Centre Hospitalier, Versailles, France.
A L
AL
Taksin
Department of Hematology, Centre Hospitalier Universitaire, Caen, France.
S
S
Cheze
Department of Hematology, Hopital Pitie Salpetriere, APHP and Paris 6 University Paris, Paris, France.
K
K
Maloum
Department of Hematology, Centre Hospitalier Universitaire, Rennes, France.
S
S
Nimuboma
Department of Oncology, Centre Rene Huguenin, Saint Cloud, France.
C
C
Soussain
Department of Hematology, Hopital Saint Antoine, APHP, and Paris 6 University Paris, Paris, France.
F
F
Isnard
Department of Hematology, Centre Hospitalier Universitaire, Tours, France.
E
E
Gyan
Departement de Recherche Clinique, Hopital Saint Louis, APHP, Paris, France.
R
R
Petit
Biostatistics Team (ECSTRA), UMR1153, Inserm, Hopital Saint Louis, APHP and Paris 7 University, Paris, France.
J
J
Lejeune
Assistance Publique-Hopitaux de Paris, Hopital Cochin, Laboratory of Hematology and Paris Descartes University, Paris, France.
V
V
Sardnal
Department of Biology, Centre Hospitalier Universitaire, Lille, France.
A
A
Renneville
Department of Biology, Centre Hospitalier Universitaire, Lille, France.
C
C
Preudhomme
Assistance Publique-Hopitaux de Paris, Hopital Cochin, Laboratory of Hematology and Paris Descartes University, Paris, France.
M
M
Fontenay
Department of Hematology, Service Hematologie Seniors, Hopital Saint Louis, APHP, and Paris 7 University Paris, Paris, France.
P
P
Fenaux
Department of Hematology, Hopital Cochin, APHP, and Paris 5 University Paris, Paris, France.
F
F
Dreyfus
D000368:Aged; D000740:Anemia / Q000517:prevention & control; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D001803:Blood Transfusion; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D004359:Drug Therapy, Combination; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000627:therapeutic use
D020533:Angiogenesis Inhibitors; D004921:Erythropoietin; D013792:Thalidomide; D000077269:Lenalidomide