Abstract
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.
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Acknowledgements
We thank Fatiha Chermat and Rosa Sapena from the Groupe Francophone des Myelodysplasies (GFM) for the management, logistical and administrative assistance. This research was supported by Celgene (Summit, NJ) and Roche (Basel, Switzerland) who provided lenalidomide and epoetin beta, respectively, along with a research grant. PF received honoraria and research funding from Celgene Corporation. FD received honoraria from Celgene and Novartis.
Author contributions
AT performed clinical research, analyzed data and wrote the paper. OK performed biological research and wrote the paper. SChev analyzed data and wrote the paper. AR, JD, AS, CR, OB-R, AB, AG-B, SW, DC, KL, BDR, DB, CG, BS, LS, VS, RP, BG, PCM, BC, CSa, RB, LL, EW, GT, KB, FG, ALT, SChez, KM, SN, CSo, FI, EG and CP performed research and wrote the paper. MF, PF and FD designed research, analyzed data and wrote the paper.
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Toma, A., Kosmider, O., Chevret, S. et al. Lenalidomide with or without erythropoietin in transfusion-dependent erythropoiesis-stimulating agent-refractory lower-risk MDS without 5q deletion. Leukemia 30, 897–905 (2016). https://doi.org/10.1038/leu.2015.296
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DOI: https://doi.org/10.1038/leu.2015.296
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