Final report of the efficacy and safety of gemtuzumab ozogamicin (Mylotarg) in patients with CD33‐positive acute myeloid leukemia in first recurrence

Richard A. Larson(University of Chicago), Eric L. Sievers(University of Washington), Edward A. Stadtmauer(University of Pennsylvania), Bob Löwenberg(Erasmus MC), Elihu H. Estey(The University of Texas MD Anderson Cancer Center), Hervé Dombret(Hôpital Saint-Louis), Matthias Theobald(Johannes Gutenberg University Mainz), D. Voliotis(University Hospital Cologne), John M. Bennett(Morpho (United States)), Maria Richie(Employment Agency), Lance Leopold(Employment Agency), Mark S. Berger(Lambeth Hospital), Matthew L. Sherman(Epix Pharmaceuticals (United States)), Michael R. Loken, Jacques J. M. van Dongen(European Council), Irwin D. Bernstein(Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa), Frederick R. Appelbaum(Fred Hutch Cancer Center), Mylotarg Study Group
Cancer
August 22, 2005
10.1002/cncr.21326
Cited by 456

Abstract

BACKGROUND: In this study, the authors analyzed the efficacy and safety of gemtuzumab ozogamicin (GO) (Mylotarg), an antibody-targeted chemotherapy for CD33-positive acute myeloid leukemia (AML). METHODS: Patients with CD33-positive AML in first recurrence were entered in 3 open-label, single-arm, Phase II studies. Patients received monotherapy with GO 9 mg/m(2) as a 2-hour intravenous infusion in 2 doses separated by 2 weeks. Patients were evaluated for remission, survival, and treatment-emergent adverse events. RESULTS: Two hundred seventy-seven patients (median age, 61 yrs) were treated with GO, and 71 patients (26%) achieved remission, which was defined as < or = 5% blasts in the bone marrow without leukemic blasts in the peripheral blood, neutrophil recovery to > or = 1500/microL, hemoglobin > or = 9 g/dL, and independence from red blood cell and platelet transfusions. Complete remission (CR) with platelet recovery (> or = 100,000/microL) or without full platelet recovery (< 100,000/microL) (CRp) was observed in 35 patients (13%) and 36 patients (13%), respectively. The median recurrence-free survival was 6.4 months for patients who achieved CR and 4.5 months for patients who achieved CRp. Although expected incidences of Grade 3 or 4 neutropenia (98%) and thrombocytopenia (99%) were observed, the incidence of Grade 3 or 4 sepsis (17%) and pneumonia (8%) was relatively low. Grade 3 or 4 hyperbilirubinemia and hepatic aspartate aminotransferase and alanine aminotransferase elevations were reported in 29%, 18%, and 9% of patients, respectively; 0.9% of patients who did not undergo prior or subsequent hematopoietic stem cell transplantation developed hepatic venoocclusive disease after GO treatment. CONCLUSIONS: When it was administered to patients with CD33-positive AML in first recurrence, single-agent GO induced a 26% remission rate with a generally acceptable safety profile.

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