title: Combined treatment with lenalidomide and epoetin alfa in lower-risk patients with myelodysplastic syndrome.
abstract: The erythropoietic effects of lenalidomide are cytokine dependent, suggesting that the erythroid hematologic improvement (HI-E) rate may be augmented by combined treatment (CT) with recombinant human erythropoietin (rhu-EPO) in myelodysplastic syndrome (MDS). In the present study, we explored the benefits of CT and the relationship between lenalidomide pharmacokinetics and hematologic toxicity in transfusion-dependent patients with low- to intermediate-1-risk MDS who failed prior rhu-EPO. In stage I, patients received 10 or 15 mg/d of lenalidomide monotherapy. At week 16, erythroid nonresponders (NRs) were eligible for CT with rhu-EPO 40 000 U/wk. Among 39 patients, HI-E response rate to monotherapy was 86% (6 of 7) in del(5q) and 25% (8 of 32) in non-del(5q) patients (10 mg, 17.7%; 15 mg, 33.3%). Twenty-three patients proceeded to CT, with 6 (26.0%) achieving HI-E. In 19 non-del(5q) patients, 4 (21.1%) showed HI-E. Mean baseline serum EPO in non-del(5q) patients was lower in monotherapy and CT responders than in NR (not statistically significant). Thrombocytopenia was significantly correlated with lenalidomide area under the plasma concentration-time curve (P = .0015), but severity of myelosuppression did not. The benefits of lenalidomide plus rhu-EPO are currently under investigation in a phase 3 Eastern Cooperative Oncology Group (ECOG)-sponsored intergroup study. This study is registered at www.clinicaltrials.gov as NCT00910858.
authors.affiliation: Department of Hematologic Malignancies, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. rami.komrokji@moffitt.org
authors.forename: Rami S
authors.initials: RS
authors.lastname: Komrokji
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Lancet
authors.forename: Arlene S
authors.initials: AS
authors.lastname: Swern
authors.forename: Nianhang
authors.initials: N
authors.lastname: Chen
authors.forename: Jennifer
authors.initials: J
authors.lastname: Paleveda
authors.forename: Richard
authors.initials: R
authors.lastname: Lush
authors.forename: Hussain I
authors.initials: HI
authors.lastname: Saba
authors.forename: Alan F
authors.initials: AF
authors.lastname: List
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004921:Erythropoietin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000473:pathology; D011994:Recombinant Proteins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D012306:Risk; D012720:Severity of Illness Index; D013792:Thalidomide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000209:etiology / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D004921:Erythropoietin; D013792:Thalidomide; D000077269:Lenalidomide