Lenalidomide in the Myelodysplastic Syndrome with Chromosome 5q Deletion
Alan List, M.D., Gordon Dewald, Ph.D., John Bennett, M.D., Aristotle Giagounidis, M.D., Azra Raza, M.D., Eric Feldman, M.D., Bayard Powell, M.D., Peter Greenberg, M.D., Deborah Thomas, M.D., Richard Stone, M.D., Craig Reeder, M.D., Kenton Wride, M.S., John Patin, M.S., Michele Schmidt, R.N., Jerome Zeldis, M.D., Robert Knight, M.D., for the Myelodysplastic Syndrome-003 Study Investigators
Background Severe, often refractory anemia is characteristicof the myelodysplastic syndrome associated with chromosome 5q31deletion. We investigated whether lenalidomide (CC5013) couldreduce the transfusion requirement and suppress the abnormal5q31– clone in patients with this disorder.
Methods One hundred forty-eight patients received 10 mg of lenalidomidefor 21 days every 4 weeks or daily. Hematologic, bone marrow,and cytogenetic changes were assessed after 24 weeks of treatmentby an intention-to-treat analysis.
Results Among the 148 patients, 112 had a reduced need for transfusions(76%; 95% confidence interval [CI], 68 to 82) and 99 patients(67%; 95% CI, 59 to 74) no longer required transfusions, regardlessof the karyotype complexity. The response to lenalidomide wasrapid (median time to response, 4.6 weeks; range, 1 to 49) andsustained; the median duration of transfusion independence hadnot been reached after a median of 104 weeks of follow-up. Themaximum hemoglobin concentration reached a median of 13.4 gper deciliter (range, 9.2 to 18.6), with a corresponding medianrise of 5.4 g per deciliter (range, 1.1 to 11.4), as comparedwith the baseline nadir value before transfusion. Among 85 patientswho could be evaluated, 62 had cytogenetic improvement, and38 of the 62 had a complete cytogenetic remission. There wascomplete resolution of cytologic abnormalities in 38 of 106patients whose serial bone marrow samples could be evaluated.Moderate-to-severe neutropenia (in 55% of patients) and thrombocytopenia(in 44%) were the most common reasons for interrupting treatmentor adjusting the dose of lenalidomide.
Conclusions Lenalidomide can reduce transfusion requirementsand reverse cytologic and cytogenetic abnormalities in patientswho have the myelodysplastic syndrome with the 5q31 deletion.(ClinicalTrials.gov number, NCT00065156
[ClinicalTrials.gov]
.)
Source Information
From the University of South Florida College of Medicine and H. Lee Moffitt Cancer Center and Research Institute, Tampa (A.L.); Mayo Clinic, Rochester, MN (G.D.); University of Rochester, Rochester, NY (J.B.); St. Johannes Hospital, Duisberg, Germany (A.G.); University of Massachusetts, Worcester (A.R.); Cornell Medical Center, New York (E.F.); Wake Forest University, Winston-Salem, NC (B.P.); Stanford University, Stanford, CA (P.G.); M.D. Anderson Cancer Center, Houston (D.T.); Dana–Farber Cancer Institute, Boston (R.S.); Mayo Clinic, Scottsdale, AZ (C.R.); and Celgene Corporation, Warren, NJ (K.W., J.P., M.S., J.Z., R.K.).
Address reprint requests to Dr. List at the Malignant Hematology Division, SRB-4, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr., Tampa, FL 33612-9497, or at heberten{at}moffitt.usf.edu.
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