JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T Author affiliations appear at the end of this article. Published online ahead of print at www.jco.org on June 27, 2016. Presented at the 56th Annual Meeting of the American Society of Hematology, San Francisco, CA, December 6-9, 2014; 13th International Symposium on Myelodysplastic Syndromes, Washington, DC, April 29-May 2, 2015; and 20th Congress of the European Hematology Association, Vienna, Austria, June 11-14, 2015. The authors had full access to the data and are fully responsible for content and editorial decisions for this manuscript. Authors’ disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article. Clinical trial information: NCT01029262. Corresponding author: Valeria Santini, MD, AOU Careggi, University of Florence, Largo Brambilla 3, Florence, Italy 50134; e-mail: valeria.santini@unifi.it. © 2016 by American Society of Clinical Oncology 0732-183X/16/3425w-2988w/$20.00 DOI: 10.1200/JCO.2015.66.0118 Randomized Phase III Study of Lenalidomide Versus Placebo in RBC Transfusion-Dependent Patients With Lower-Risk Non-del(5q) Myelodysplastic Syndromes and Ineligible for or Refractory to Erythropoiesis-Stimulating Agents Valeria Santini, Antonio Almeida, Aristoteles Giagounidis, Stefanie Gr¨ opper, Anna Jonasova, Norbert Vey, Ghulam J. Mufti, Rena Buckstein, Moshe Mittelman, Uwe Platzbecker, Ofer Shpilberg, Ron Ram, Consuelo del Cañizo, Norbert Gattermann, Keiya Ozawa, Alberto Risueño, Kyle J. MacBeth, Jianhua Zhong, Francis S´ eguy, Albert Hoenekopp, C.L. Beach, and Pierre Fenaux See accompanying editorial on page 2956 A B S T R A C T Purpose This international phase III, randomized, placebo-controlled, double-blind study assessed the effi- cacy and safety of lenalidomide in RBC transfusion–dependent patients with International Prog- nostic Scoring System lower-risk non-del(5q) myelodysplastic syndromes ineligible for or refractory to erythropoiesis-stimulating agents. Patients and Methods In total, 239 patients were randomly assigned (2:1) to treatment with lenalidomide (n = 160) or placebo (n = 79) once per day (on 28-day cycles). The primary end point was the rate of RBC transfusion independence (TI) $ 8 weeks. Secondary end points were RBC-TI $ 24 weeks, duration of RBC-TI, erythroid response, health-related quality of life (HRQoL), and safety. Results RBC-TI $ 8 weeks was achieved in 26.9% and 2.5% of patients in the lenalidomide and placebo groups, respectively (P , .001). Ninety percent of patients achieving RBC-TI responded within 16 weeks of treatment. Median duration of RBC-TI with lenalidomide was 30.9 weeks (95% CI, 20.7 to 59.1). Transfusion reduction of $ 4 units packed RBCs, on the basis of a 112-day assessment, was 21.8% in the lenalidomide group and 0% in the placebo group. Higher response rates were observed in patients with lower baseline endogenous erythropoietin # 500 mU/mL (34.0% v 15.5% for . 500 mU/mL). At week 12, mean changes in HRQoL scores from baseline did not differ signif- icantly between treatment groups, which suggests that lenalidomide did not adversely affect HRQoL. Achievement of RBC-TI $ 8 weeks was associated with significant improvements in HRQoL (P , .01). The most common treatment-emergent adverse events were neutropenia and thrombocytopenia. Conclusion Lenalidomide yields sustained RBC-TI in 26.9% of RBC transfusion–dependent patients with lower- risk non-del(5q) myelodysplastic syndromes ineligible for or refractory to erythropoiesis-stimulating agents. Response to lenalidomide was associated with improved HRQoL. Treatment-emergent ad- verse event data were consistent with the known safety profile of lenalidomide. J Clin Oncol 34:2988-2996. © 2016 by American Society of Clinical Oncology INTRODUCTION For most patients with lower-risk myelodysplastic syndromes (MDS), anemia represents the main therapeutic challenge. 1,2 Anemia often requires repeated RBC transfusions with cumulative asso- ciated morbidity. 3 In patients without a deletion 5q [del(5q)], erythropoiesis-stimulating agents (ESAs) remain the first-line therapy 4-6 ; however, ESAs are recommended only for patients with lower-risk non-del(5q) and serum erythropoietin (EPO) levels # 500 mU/mL. 4,7 Moreover, most responses to ESAs are lost over time. 8 Although azacitidine and decitabine are approved in the United States and other countries in this setting, 2988 © 2016 by American Society of Clinical Oncology VOLUME 34 • NUMBER 25 • SEPTEMBER 1, 2016 Downloaded from ascopubs.org by 52.73.204.196 on May 17, 2022 from 052.073.204.196 Copyright © 2022 American Society of Clinical Oncology. All rights reserved.