Long-Term Disease-Free Survival After Gemtuzumab, Intermediate-Dose Cytarabine, and Mitoxantrone in Patients With CD33+Primary Resistant or Relapsed Acute Myeloid Leukemia

Abstract

PurposeTo determine the antitumor activity and safety of a combination of gemtuzumab ozogamicin (GO), intermediate-dose cytarabine, and mitoxantrone (MIDAM) in patients with refractory or relapsed CD33+acute myeloid leukemia (AML).Patients and MethodsWe treated 62 patients with refractory (n = 18) or relapsed (n = 44) CD33+AML. Median age was 55.5 years. Salvage regimen consisted of GO 9 mg/m2on day 4, cytarabine 1 g/m2every 12 hours on days 1 through 5, and mitoxantrone 12 mg/m2/d on days 1 through 3. Median follow-up time was 26.5 months.ResultsThirty-one patients (50%) achieved complete remission (CR), and eight patients (13%) had CR with delayed platelet recovery (CRp); the overall response (OR; CR + CRp) rate was 63%. A significantly higher OR rate was achieved in patients who had relapsed versus refractory AML (73% v 39%, respectively; P = .007) and patients with CD33 expression more than 98% of the blast population versus less than 98% (79% v 52.3%, respectively; P = .03). The overall, event-free, and disease-free survival rates were 41%, 33%, and 53% at 2 years, respectively. Leukocytosis more than 20,000/μL at MIDAM therapy, high-risk cytogenetics, and absence of postremission therapy were adverse prognostic factors. Age, disease status, and/or CD33 expression did not influence survival parameters. Four early toxic deaths occurred; a grade 3 to 4 hyperbilirubinemia rate of 16% was observed, and two patients had veno-occlusive disease (3%).ConclusionThe MIDAM regimen seems to be an effective salvage regimen for refractory/relapsed CD33+AML patients. These encouraging results support the need for a randomized phase III trial before considering this combination of GO and chemotherapy as superior or the standard of care treatment for refractory/relapsed CD33+AML patients.