title: A randomized phase 3 study of lenalidomide versus placebo in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with del5q.
abstract: This phase 3, randomized, double-blind study assessed the efficacy and safety of lenalidomide in 205 red blood cell (RBC) transfusion-dependent patients with International Prognostic Scoring System Low-/Intermediate-1-risk del5q31 myelodysplastic syndromes. Patients received lenalidomide 10 mg/day on days 1-21 (n = 69) or 5 mg/day on days 1-28 (n = 69) of 28-day cycles; or placebo (n = 67). Crossover to lenalidomide or higher dose was allowed after 16 weeks. More patients in the lenalidomide 10- and 5-mg groups achieved RBC-transfusion independence (TI) for ≥ 26 weeks (primary endpoint) versus placebo (56.1% and 42.6% vs 5.9%; both P < .001). Median duration of RBC-TI was not reached (median follow-up, 1.55 years), with 60% to 67% of responses ongoing in patients without progression to acute myeloid leukemia (AML). Cytogenetic response rates were 50.0% (10 mg) versus 25.0% (5 mg; P = .066). For the lenalidomide groups combined, 3-year overall survival and AML risk were 56.5% and 25.1%, respectively. RBC-TI for ≥ 8 weeks was associated with 47% and 42% reductions in the relative risks of death and AML progression or death, respectively (P = .021 and .048). The safety profile was consistent with previous reports. Lenalidomide is beneficial and has an acceptable safety profile in transfusion-dependent patients with Low-/Intermediate-1-risk del5q myelodysplastic syndrome. This trial was registered at www.clinicaltrials.gov as #NCT00179621.
authors.affiliation: Hopital Avicenne, Assistance Publique-Hôpitaux de Paris, Université Paris XIII, Bobigny, France. pierre.fenaux@avc.aphp.fr
authors.forename: Pierre
authors.initials: P
authors.lastname: Fenaux
authors.forename: Aristoteles
authors.initials: A
authors.lastname: Giagounidis
authors.forename: Dominik
authors.initials: D
authors.lastname: Selleslag
authors.forename: Odile
authors.initials: O
authors.lastname: Beyne-Rauzy
authors.forename: Ghulam
authors.initials: G
authors.lastname: Mufti
authors.forename: Moshe
authors.initials: M
authors.lastname: Mittelman
authors.forename: Petra
authors.initials: P
authors.lastname: Muus
authors.forename: Peter
authors.initials: P
authors.lastname: Te Boekhorst
authors.forename: Guillermo
authors.initials: G
authors.lastname: Sanz
authors.forename: Consuelo
authors.initials: C
authors.lastname: Del Cañizo
authors.forename: Agnes
authors.initials: A
authors.lastname: Guerci-Bresler
authors.forename: Lars
authors.initials: L
authors.lastname: Nilsson
authors.forename: Uwe
authors.initials: U
authors.lastname: Platzbecker
authors.forename: Michael
authors.initials: M
authors.lastname: Lübbert
authors.forename: Bruno
authors.initials: B
authors.lastname: Quesnel
authors.forename: Mario
authors.initials: M
authors.lastname: Cazzola
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.forename: David
authors.initials: D
authors.lastname: Bowen
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schlegelberger
authors.forename: Carlo
authors.initials: C
authors.lastname: Aul
authors.forename: Robert
authors.initials: R
authors.lastname: Knight
authors.forename: John
authors.initials: J
authors.lastname: Francis
authors.forename: Tommy
authors.initials: T
authors.lastname: Fu
authors.forename: Eva
authors.initials: E
authors.lastname: Hellström-Lindberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D020732:Cytogenetic Analysis; D004311:Double-Blind Method; D017707:Erythrocyte Transfusion; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000628:therapy; D011379:Prognosis; D016019:Survival Analysis; D013792:Thalidomide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D013792:Thalidomide; D000077269:Lenalidomide