Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse.
OBJECTIVE
Three open-label, multicenter trials were conducted to evaluate the efficacy and safety of single-agent Mylotarg (gemtuzumab ozogamicin; CMA-676; Wyeth Laboratories, Philadelphia, PA), an antibody-targeted chemotherapy agent, in patients with CD33-positive acute myeloid leukemia (AML) in untreated first relapse.


METHODS
The study population comprised 142 patients with AML in first relapse with no history of an antecedent hematologic disorder and a median age of 61 years. All patients received Mylotarg as a 2-hour intravenous infusion, at a dose of 9 mg/m(2), at 2-week intervals for two doses. Patients were evaluated for remission, survival, and treatment-emergent adverse events.


RESULTS
Thirty percent of patients treated with Mylotarg obtained remission as characterized by 5% or less blasts in the marrow, recovery of neutrophils to at least 1,500/microL, and RBC and platelet transfusion independence. Although patients treated with Mylotarg had relatively high incidences of myelosuppression, grade 3 or 4 hyperbilirubinemia (23%), and elevated hepatic transaminase levels (17%), the incidences of grade 3 or 4 mucositis (4%) and infections (28%) were relatively low. There was a low incidence of severe nausea and vomiting (11%) and no treatment-related cardiotoxicity, cerebellar toxicity, or alopecia. Many patients received Mylotarg on an outpatient basis (38% and 41% of patients for the first and second doses, respectively). Among the 142 patients, the median total duration of hospitalization was 24 days; 16% of patients required 7 days of hospitalization or less.


CONCLUSIONS
Administration of the antibody-targeted chemotherapy agent Mylotarg to patients with CD33-positive AML in first relapse induces complete remissions with what appears to be a favorable safety profile.
Sievers
E L
EL
Clinical Research Division, Fred Hutchinson Cancer Research Center, Department of Pediatrics, University of Washington, and Hematologics Inc, Seattle WA.
Larson
R A
RA
Stadtmauer
E A
EA
Estey
E
E
Löwenberg
B
B
Dombret
H
H
Karanes
C
C
Theobald
M
M
Bennett
J M
JM
Sherman
M L
ML
Berger
M S
MS
Eten
C B
CB
Loken
M R
MR
van Dongen
J J
JJ
Bernstein
I D
ID
Appelbaum
F R
FR
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D018572:Disease-Free Survival; D005060:Europe / Q000453:epidemiology; D005260:Female; D000079982:Gemtuzumab; D006801:Humans; D000922:Immunotoxins / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009656:North America / Q000453:epidemiology; D011379:Prognosis; D012008:Recurrence; D063268:Sialic Acid Binding Ig-like Lectin 3; D015996:Survival Rate
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D000922:Immunotoxins; D063268:Sialic Acid Binding Ig-like Lectin 3; D000079982:Gemtuzumab