Long-term disease-free survival after gemtuzumab, intermediate-dose cytarabine, and mitoxantrone in patients with CD33(+) primary resistant or relapsed acute myeloid leukemia.
OBJECTIVE
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).


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/m(2) on day 4, cytarabine 1 g/m(2) every 12 hours on days 1 through 5, and mitoxantrone 12 mg/m(2)/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/microL 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%).


CONCLUSIONS
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.
Chevallier
Patrice
P
Service d'Hématologie Clinique, Centre Hospitalier Universitaire (CHU) Hotel-Dieu, Nantes, France. patrice.chevallier@chu-nantes.fr
Delaunay
Jacques
J
Turlure
Pascal
P
Pigneux
Arnaud
A
Hunault
Mathilde
M
Garand
Richard
R
Guillaume
Thierry
T
Avet-Loiseau
Herve
H
Dmytruk
Nathalia
N
Girault
Stephane
S
Milpied
Noel
N
Ifrah
Norbert
N
Mohty
Mohamad
M
Harousseau
Jean-Luc
JL
D000617:Aminoglycosides / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD / Q000032:analysis*; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D005602:France / Q000453:epidemiology; D000079982:Gemtuzumab; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D012008:Recurrence; D016879:Salvage Therapy; D063268:Sialic Acid Binding Ig-like Lectin 3; D013997:Time Factors; D017211:Treatment Failure; D016896:Treatment Outcome
D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D063268:Sialic Acid Binding Ig-like Lectin 3; D003561:Cytarabine; D000079982:Gemtuzumab; D008942:Mitoxantrone