Efficacy and tolerability of gemtuzumab ozogamicin (anti-CD33 monoclonal antibody, CMA-676, Mylotarg) in children with relapsed/refractory myeloid leukemia.
BACKGROUND
Gemtuzumab ozogamicin (GO) is a cytotoxic anti-CD33 monoclonal antibody that has given promising preliminary results in adult myeloid CD33+ AML. We conducted a retrospective multicenter study of 12 children treated with GO on a compassionate basis (median age 5.5 y). Three patients (2 MDS/AML, 1 JMML) were refractory to first-line treatment, 8 patients with de novo AML were in refractory first relapse, and one patient with de novo AML was in 2nd relapse after stem cell transplantation (SCT). CD33 expression exceeded 20% in all cases.


METHODS
GO was administered alone, at a unit dose of 3-9 mg/m2, once (3 patients), twice (3 patients), three (5 patients) or five times (1 patient). Mean follow-up was 128 days (8-585 d).


RESULTS
There were three complete responses (25%) leading to further curative treatment (SCT). Treatment failed in the other nine patients, and only one patient was alive at the end of follow-up. NCI-CTC grade III/IV adverse events comprised hematological toxicity (n = 12), hypertransaminasemia (n = 2), allergy and hyperbilirubinemia (1 case each). There was only one major adverse event (grade IV allergy). No case of sinusoidal obstruction syndrome occurred.


CONCLUSIONS
These results warrant a prospective trial of GO in a larger population of children with AML.
Brethon
Benoit
B
Unité de Pédiatrie à Orientation Hématologique, Hôpital Saint-Louis, Paris, France. benoit.brethon@sls.aphp.fr
Auvrignon
Anne
A
Galambrun
Claire
C
Yakouben
Karima
K
Leblanc
Thierry
T
Bertrand
Yves
Y
Leverger
Guy
G
Baruchel
André
A
D000293:Adolescent; D000617:Aminoglycosides / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005260:Female; D000079982:Gemtuzumab; D006801:Humans; D000922:Immunotoxins / Q000009:adverse effects / Q000627:therapeutic use*; D007223:Infant; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D008297:Male; D012008:Recurrence; D012074:Remission Induction / Q000379:methods; D012189:Retrospective Studies; D063268:Sialic Acid Binding Ig-like Lectin 3
D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000970:Antineoplastic Agents; C571163:CD33 protein, human; D000922:Immunotoxins; D063268:Sialic Acid Binding Ig-like Lectin 3; D000079982:Gemtuzumab