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

BACKGROUND. In this study, the authors analyzed the efficacy and safety of gemtuzumab ozogamicin (GO) (Mylotarg (R)), 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 : 5% blasts in the bone marrow without leukemic blasts in the peripheral blood, neutrophil recovery to 1500/mu L, hemoglobin >= 9 g/dL, and independence from red blood cell and platelet transfusions. Complete remission (CR) with platelet recovery (>= 100,000/mu L) or without full platelet recovery (< 100,000/mu L) (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.