A phase II study of decitabine and gemtuzumab ozogamicin in newly diagnosed and relapsed acute myeloid leukemia and high-risk myelodysplastic syndrome

• Published in: Leukemia Vol. 30; no. 2; pp. 268 - 273
• Main Authors: Daver, N, Kantarjian, H, Ravandi, F, Estey, E, Wang, X, Garcia-Manero, G, Jabbour, E, Konopleva, M, O'Brien, S, Verstovsek, S, Kadia, T, Dinardo, C, Pierce, S, Huang, X, Pemmaraju, N, Diaz-Pines-Mateo, M, Cortes, J, Borthakur, G
• Format: Journal Article
• Language: English
• Published: London Springer Science and Business Media LLC 01.02.2016; Nature Publishing Group UK; Nature Publishing Group
• Subjects: 5-aza-2'-deoxycytidine; 6.1 Pharmaceuticals; 692/699/1541/1990/283/1897; 80 and over; Acute; Acute myeloid leukemia; Adult; Aged; Aged, 80 and over; Aminoglycosides; Aminoglycosides - administration & dosage; Aminoglycosides - adverse effects; Antibodies; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antineoplastic Combined Chemotherapy Protocols; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Azacitidine; Azacitidine - administration & dosage; Azacitidine - adverse effects; Azacitidine - analogs & derivatives; Biomedical and Clinical Sciences; Calicheamicin; Cancer; Cancer Research; Cardiovascular medicine and haematology; Chemotherapy; Childhood Leukemia; Chromatin; Clinical Research; Clinical Sciences; Clinical Trials and Supportive Activities; Critical Care Medicine; Decitabine; Drug therapy; Epitopes; Evaluation of treatments and therapeutic interventions; Female; Gemtuzumab; Gemtuzumab ozogamicin; Good Health and Well Being; Hematology; Hemorrhage; Heterogeneity; Humanized; Humans; Immunology; Induction therapy; Intensive; Internal Medicine; Leukemia; Leukemia, Myeloid, Acute; Leukemia, Myeloid, Acute - drug therapy; Male; Medicine; Medicine & Public Health; Middle Aged; Monoclonal; Monoclonal antibodies; Mucositis; Myelodysplastic syndrome; Myelodysplastic Syndromes; Myelodysplastic Syndromes - drug therapy; Myelofibrosis; Myeloid; Nausea; Oncology; Oncology and Carcinogenesis; Oncology, Experimental; original-article; Orphan Drug; Patients; Pediatric; Pediatric Cancer; Pharmacology, Experimental; Rare Diseases; Remission; Remission (Medicine); Sialic Acid Binding Ig-like Lectin 3; Sialic Acid Binding Ig-like Lectin 3 - analysis; Targeted cancer therapy
• ISSN: 0887-6924; 1476-5551; 1476-5551
• DOI: 10.1038/leu.2015.244

Decitabine may open the chromatin structure of leukemia cells making them accessible to the calicheamicin epitope of gemtuzumab ozogamicin (GO). A total of 110 patients (median age 70 years; range 27–89 years) were treated with decitabine and GO in a trial designed on model-based futility to accommodate subject heterogeneity: group 1: relapsed/refractory acute myeloid leukemia (AML) with complete remission duration (CRD) <1 year ( N =28, 25%); group 2: relapsed/refractory AML with CRD ⩾1 year ( N =5, 5%); group 3: untreated AML unfit for intensive chemotherapy or untreated myelodysplastic syndrome (MDS) or untreated myelofibrosis (MF; N =57, 52%); and group 4: AML evolving from MDS or relapsed/refractory MDS or MF ( N =20, 18%). Treatment consisted of decitabine 20 mg/m 2 daily for 5 days and GO 3 mg/m 2 on day 5. Post-induction therapy included five cycles of decitabine+GO followed by decitabine alone. Complete remission (CR)/CR with incomplete count recovery was achieved in 39 (35%) patients; group 1= 5/28 (17%), group 2=3/5 (60%), group 3=24/57 (42%) and group 4=7/20 (35%). The 8-week mortality in groups 3 and 4 was 16% and 10%, respectively. Common drug-related adverse events included nausea, mucositis and hemorrhage. Decitabine and GO improved the response rate but not overall survival compared with historical outcomes in untreated AML ⩾60 years.