CMA-676 (gemtuzumab zogamicin) is an
antibody-targeted chemotherapeutic agent consisting of a humanized
anti-CD33 antibody linked to calicheamicin, a potent cytotoxic agent.
This agent was designed to effectively deliver cytotoxic chemotherapy
to acute myelogenous leukemia (AML) cells, while limiting
In a phase II trial, CMA-676 was administered intravenously (IV) at a
dose of 9 mg/m² every 2 weeks for two doses. Eligible patients
had AML in first relapse following an initial remission of at least 6
months; those with secondary AML or preceding myelodysplastic
syndromes were excluded.
A total of 59 patients entered the study prior to December 31, 1998.
Median age was 53 years (range, 22 to 81 years). Of the 59 patients,
20 (34%) achieved a remission (characterized by < 5% blasts in the
marrow, 1,500/µL neutrophils, and platelet transfusion
independence prior to any additional post-remission therapy).
Median survival for all patients was 161 days, while that of patients
achieving remission was not reached by the data cutoff date of March
15, 1999. Of the 20 patients who achieved remission, 12 remained
relapse free, with a median follow-up of 238 days (range, 21 to 608 days).
Post-remission therapy was administered to 15 of the 20 patients
(bone marrow transplantation [BMT] in 12 patients, chemotherapy in
3). Of the 15 patients, 1 died during a complete response (CR) due to
transplant complications and 1 relapsed following allogeneic BMT. Two
patients experienced a relapse following autologous BMT, with 1
patient expiring from progressive AML and 1 patient relapsing after
receiving chemotherapy. Of the 5 patients who did not receive post-remission
therapy, 3 relapsed and 2 remain leukemia free 4.5 and 3.5 months,
respectively, after the first dose of CMA-676.
Overall, CMA-676 was well tolerated, as indicated by hospitalization
for £ 1 week for 15 patients during
treatment (ending 28 days after the last dose of CMA-676; excluding
patients who expired during the same period). Severe (National Cancer
Institute [NCI] grade 3-4) mucositis was not observed with CMA-676 treatment.
Adverse events following CMA-676 infusion frequently included
self-limited fever, chills, and infrequently consisted of hypotension
and shortness of breath. Almost all patients experienced grade 4
neutropenia and thrombocytopenia. Transient grade 3-4 increases in
bilirubin and/or hepatic transaminases occurred in 9 patients.
Individual patients experienced severe bone pain, intussusception,
diabetes insipidus, seizures, exacerbation of disseminated
intravascular coagulation, and intracerebral bleeding.
CONCLUSION: Antibody-targeted chemotherapy of AML cells via
administration of CMA-676 as a single agent is associated with an
acceptable safety profile while achieving