title: Lenalidomide combined with intensive chemotherapy in acute myeloid leukemia and higher-risk myelodysplastic syndrome with 5q deletion. Results of a phase II study by theGroupe Francophone Des Myélodysplasies.
abstract: Patients with acute myeloblastic leukemia or higher risk myelodysplastic syndromes with 5q deletion (generally within a complex karyotype) respond poorly to intensive chemotherapy and have very poor survival. In this population, we evaluated escalating doses of lenalidomide combined with intensive chemotherapy in a phase II study. Treatment consisted of daunorubicin (45 mg/m2/day, days 1-3 in cohort 1, escalated to 60 mg/m2/day, days 1-3 in cohorts 2 and 3) combined with cytosine arabinoside (200 mg/m2/day, days 1-7) and lenalidomide (10 mg/day, days 1-21 in cohorts 1 and 2, escalated to 25 mg/day, days 1-21 in cohort 3). Eighty-two patients with 5q deletion were enrolled, including 62 with acute myeloblastic leukemia, 62/79 (78%) of whom had a complex karyotype (median 7 cytogenetic abnormalities, all but 2 of them monosomal) and three had unknown karyotypes. Thirty-eight patients (46%) achieved complete remission and the overall response rate was 58.5%. Among the 62 patients with a complex karyotype, 27 achieved complete remission (44%) and 21 had cytogenetic responses. A lower response rate was observed in patients with acute myeloblastic leukemia but other pretreatment factors, including cytogenetic complexity and treatment cohort, did not significantly influence response. Fifteen patients underwent allogeneic stem cell transplantation, including 11 patients in first remission. The 1-year cumulative incidence of relapse was 64.6% and the median overall survival was 8.2 months. By comparison with conventional intensive chemotherapy, the treatment protocol we used appeared to produce higher hematologic and cytogenetic complete remission rates in patients with very poor cytogenetics, but response duration was short in this very poor risk population, highlighting the need for better post-induction strategies.Clinical trial registry number: NCT00885508.
authors.affiliation: Hôpital St Louis, Assistance Publique-Hôpitaux de Paris and Paris 7 University, Paris, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Ades
authors.affiliation: Institut Paoli-Calmettes, Marseille, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Prebet
authors.affiliation: Service d'Hématologie, Rouen, France.
authors.forename: Aspasia
authors.initials: A
authors.lastname: Stamatoullas
authors.affiliation: Hématologie, CHU de Toulouse, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Recher
authors.affiliation: Service d'Hématologie, Clermont-Ferrand, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Guieze
authors.affiliation: Hôpital Saint Louis, Paris, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Raffoux
authors.affiliation: Service d'Hématologie Clinique et de Thérapie Cellulaire, CHU de Bordeaux Hôpital du Haut-Lévêque, Pessac, France.
authors.forename: Krimo
authors.initials: K
authors.lastname: Bouabdallah
authors.affiliation: Service d'Hématologie, Angers, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Hunault
authors.affiliation: Service d'Hématologie, Lyon, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Wattel
authors.affiliation: Service d'Hématologie, Lens, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Stalnikiewicz
authors.affiliation: Hôpital Henri Mondor, Créteil, France.
authors.forename: Andrea
authors.initials: A
authors.lastname: Toma
authors.affiliation: Hôpital Saint Louis, Paris, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Dombret
authors.affiliation: Institut Paoli-Calmettes, Marseille, France.
authors.forename: Norbert
authors.initials: N
authors.lastname: Vey
authors.affiliation: Hôpital St Louis, Assistance Publique-Hôpitaux de Paris and Paris 7 University, Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Sebert
authors.affiliation: Hopital Avicenne and Paris 13 University, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Gardin
authors.affiliation: SBIM, Hôpital Saint Louis, Paris, France.
authors.forename: Cendrine
authors.initials: C
authors.lastname: Chaffaut
authors.affiliation: SBIM, Hôpital Saint Louis, Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chevret
authors.affiliation: Hôpital St Louis, Assistance Publique-Hôpitaux de Paris and Paris 7 University, Paris, France pierre.fenaux@aphp.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Fenaux
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome
chemical_list: D013792:Thalidomide; D000077269:Lenalidomide