Originally published as JCO Early Release 10.1200/JCO.2007.15.9764 on October 14 2008

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

Patrice Chevallier, Jacques Delaunay, Pascal Turlure, Arnaud Pigneux, Mathilde Hunault, Richard Garand, Thierry Guillaume, Herve Avet-Loiseau, Nathalia Dmytruk, Stephane Girault, Noel Milpied, Norbert Ifrah, Mohamad Mohty, Jean-Luc Harousseau

From the Service d'Hématologie Clinique, Centre Hospitalier Universitaire (CHU) Hotel-Dieu; Service d'Hématologie Biologie, CHU de Nantes, Nantes; Service d'Hematologie Clinique, CHU de Limoges, Limoges; Service d'Hematologie Clinique, CHU de Bordeaux, Bordeaux; and Service d'Hematologie Clinique, CHU d'Angers, Angers, France

Corresponding author: Patrice Chevallier, MD, Service d'Hématologie Clinique, Centre Hospitalier Universitaire, Place Alexis Ricordeau, 44093 Nantes Cedex 01, France; e-mail: patrice.chevallier{at}chu-nantes.fr

Purpose To 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 Methods We 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/m² on day 4, cytarabine 1 g/m² every 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.

Results Thirty-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%).

Conclusion The 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.

published online ahead of print at www.jco.org on October 13, 2008.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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