title: Idarubicin and cytarabine in combination with gemtuzumab ozogamicin (IAGO) for untreated patients with high-risk MDS or AML evolved from MDS: a phase II study from the EORTC and GIMEMA Leukemia Groups (protocol 06013).
abstract: The primary objective of this trial was to assess the feasibility, toxicity profile, and antitumor activity of gemtuzumab ozogamicin (GO) combined with a chemotherapy remission-induction regimen in adults with untreated high-risk myelodysplastic syndrome (HR-MDS) or secondary acute myeloid leukemia (sAML). In this phase II trial, 30 patients with median age of 58 years received 1 day of GO as a 1-h infusion at the dose level of 5 mg/m(2) on day 7 of the remission-induction course further consisting of a continuous infusion of cytarabine 100 mg/m(2)/day for 10 days and idarubicin 12 mg/m(2)/day on days 1, 3, and 5. A consolidation course, consisting of intermediate-dose cytarabine (A) and idarubicin (I) followed by hematopoietic stem cell transplantation (HSCT) was planned for patients in complete remission (CR). The primary endpoints were response rate (CR/CRi) and severe toxicity rate. The secondary endpoint(s) were survival and progression-free survival (PFS) from start of treatment. Thirteen patients (43 %) achieved CR (eight patients) or CR with incomplete hematopoietic recovery (CRi) (five patients). In patients who achieved CR or CRi, the median time to recovery of neutrophils to 0.5 × 10(9)/l and of platelets to >50 × 10(9)/l was 29 and 30 days, respectively. Grade 3 to 4 severe toxicities occurred in nine patients. The most prominent was liver toxicity, as shown by elevated bilirubin levels in 16 patients and one case of nonfatal veno-occlusive disease (VOD). All 13 patients with CR/CRi received consolidation therapy, which was followed by allogeneic HSCT in five patients and autologous HSCT in three patients. According to the statistical design of the study, the idarubicin and cytarabine in combination with gemtuzumab ozogamicin (IAGO) regimen did not show sufficient activity to warrant further exploration of this regimen in adult patients with HR-MDS or sAML.
authors.affiliation: Radboud University Medical Centre, Nijmegen, The Netherlands. theo.dewitte@radboudumc.nl.|Department of Tumorimmunology, Radboud Institute of Molecular Life Sciences, Radboud University Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands. theo.dewitte@radboudumc.nl.
authors.forename: Theo
authors.initials: T
authors.lastname: de Witte
authors.affiliation: EORTC Headquarters, Brussels, Belgium.
authors.forename: Stefan
authors.initials: S
authors.lastname: Suciu
authors.affiliation: EORTC Headquarters, Brussels, Belgium.
authors.forename: Liv
authors.initials: L
authors.lastname: Meert
authors.affiliation: Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Constantijn
authors.initials: C
authors.lastname: Halkes
authors.affiliation: St Jan's Hospital, Brugge, Belgium.
authors.forename: Dominik
authors.initials: D
authors.lastname: Selleslag
authors.affiliation: Institut J. Bordet (ULB), Brussels, Belgium.
authors.forename: Dominique
authors.initials: D
authors.lastname: Bron
authors.affiliation: Tor Vergata University Hospital, Rome, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Amadori
authors.affiliation: Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Roel
authors.initials: R
authors.lastname: Willemze
authors.affiliation: Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Petra
authors.initials: P
authors.lastname: Muus
authors.affiliation: University of Liege, Liege, Belgium.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Baron
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D064591:Allografts; D000617:Aminoglycosides / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D064592:Autografts; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D000079982:Gemtuzumab; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000401:mortality / Q000628:therapy; D015996:Survival Rate
chemical_list: D000617:Aminoglycosides; D061067:Antibodies, Monoclonal, Humanized; D003561:Cytarabine; D000079982:Gemtuzumab; D015255:Idarubicin
keywords: Chronic myelomonocytic leukemia; Cytogenetic risk score; Gemtuzumab ozogamicin; High-risk myelodysplastic syndromes; Liver toxicity; Secondary acute myeloid leukemia