Journal Article

High efficacy and safety profile of fractionated doses of Mylotarg as induction therapy in patients with relapsed acute myeloblastic leukemia: a prospective study of the alfa group

Farhat, H, Bouabdallah, R, Pautas, C, Legrand, O, Reman, O, Gardin, C, Taksin, A-L, Turlure, P, Dombret, H, Thomas, X, Castaigne, S, Contentin, N, Varet, B, Raffoux, E, de Revel, T, Pousset, F, de Botton, S, Chevret, S

2007

Overview

Pivotal phase II studies in acute myeloblastic leukemia (AML) patients in first relapse have used gemtuzumab ozogamicin (GO) (Mylotarg) at a dose of 9 mg/m(2) on days 1 and 14. These studies showed a 26% response rate (13% complete remission (CR) and 13% CRp (complete remission with incomplete platelet recovery)) but with high degree of hematological and liver toxicities. Based on in vitro studies showing a re-expression of CD33 antigenic sites on the cell surface of blasts cells after exposure to GO, we hypothesized that fractionated doses of GO may be efficient and better tolerated. Fifty-seven patients with AML in first relapse received GO at a dose of 3 mg/m(2) on days 1, 4 and 7 for one course. Fifteen patients (26%) achieved CR and four (7%) CRp. Remission rate correlated strongly with P-glycoprotein and MRP1 activities. The median relapse-free survival was 11 months, similar for CR or CRp patients. Median duration of neutropenia < 500/microl and thrombocytopenia < 50,000/microl were, respectively, 23 and 21 days. No grade 3 or 4 liver toxicity was observed. No veno-occlusive disease occurred after GO or after hematopoietic stem cell transplantation given after GO in seven patients. Mylotarg administered in fractionated doses demonstrated an excellent efficacy/safety profile.

• Publisher: Nature Publishing,Nature Publishing Group
• Subject: Adult / Aged / Aged, 80 and over / Aminoglycosides - administration & dosage / Aminoglycosides - adverse effects / Antibodies, Monoclonal - administration & dosage / Antibodies, Monoclonal - adverse effects / Antibodies, Monoclonal, Humanized / Antigens, CD - blood / Antigens, Differentiation, Myelomonocytic - blood / Antineoplastic Agents - administration & dosage / Antineoplastic Agents - adverse effects / ATP-Binding Cassette, Sub-Family B, Member 1 - blood / Biological and medical sciences / Disease-Free Survival / Drug Administration Schedule / Hematologic and hematopoietic diseases / Humans / Leukemia, Myeloid, Acute - drug therapy / Leukemia, Myeloid, Acute - immunology / Leukemia, Myeloid, Acute - mortality / Leukemia, Myeloid, Acute - pathology / Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis / Medical sciences / Middle Aged / Multidrug Resistance-Associated Proteins - blood / Recurrence / Remission Induction / Sialic Acid Binding Ig-like Lectin 3