Lenalidomide-Epoetin Alfa Versus Lenalidomide Monotherapy in Myelodysplastic Syndromes Refractory to Recombinant Erythropoietin

H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL. Dana Farber Cancer Institute-ECOG-ACRIN Biostatistics Center, Boston, MA. Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY. University of Rochester, New York, NY. Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH. Northwestern University, Chicago, IL. Saint John's Hospital, Maplewood, MN. Penn State Cancer Center, Hershey, PA. University of Pennsylvania, Philadelphia, PA. University of Wisconsin, Madison, WI. Waukesha Memorial Hospital, Waukesha, WI. City of Hope National Medical Center, Duarte, CA. Karmanos Cancer Institute, Wayne State University, Detroit, MI. Mayo Clinic, Rochester, MN. Leukemia Service, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2021;:Jco2001691
PURPOSE Impaired response to erythropoietin underlies ineffective erythropoiesis and anemia in myelodysplastic syndromes (MDS). We investigated whether treatment with lenalidomide (LEN), which augments erythropoietin receptor signaling in vitro, can restore and improve hemoglobin response to epoetin (EPO) alfa in patients with lower-risk, non-del(5q) MDS who have anemia that is refractory to or have low probability of benefit from treatment with recombinant erythropoietin. METHODS In a phase III, US intergroup trial, we randomly assigned patients to receive either LEN and EPO alfa or LEN alone following stratification by serum erythropoietin concentration and prior erythropoietin treatment. RESULTS A total of 195 evaluable patients were randomly assigned: 99 patients to the LEN-EPO alfa cohort and 96 to LEN alone. After four cycles of treatment, the primary end point of major erythroid response (MER) was significantly higher (28.3%) with the combination compared with LEN alone (11.5%) (P = .004). Among 136 patients who completed 16 weeks of study treatment, 38.9% and 15.6% achieved MER, respectively (P = .004). Additionally, minor erythroid response was achieved in 18.2% and 20.8% of patients, for an overall erythroid response rate of 46.5% versus 32.3%. Among LEN nonresponders, 38 crossed over to the addition of EPO alfa with 10 patients (26.3%) achieving a MER. Responses to the combined treatment were highly durable with a median MER duration of 23.8 months compared with 13 months with LEN alone. CONCLUSION LEN restores sensitivity to recombinant erythropoietin in growth factor-insensitive, lower-risk, non-del(5q) MDS, to yield a significantly higher rate and duration of MER compared with LEN alone (funded by the National Cancer Institute; E2905 ClinicalTrials.gov identifier: NCT02048813).
Study details
Language : eng
Credits : Bibliographic data from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine