The US Food and Drug Administration recently approved gemtuzumab
ozogamicin (Mylotarg) for the treatment of patients 60 years of age
and older who are in first relapse with CD33-positive acute myeloid
leukemia (AML) and are not considered candidates for cytotoxic
chemotherapy. Designated an orphan drug in November 1999, gemtuzumab
is the first drug specifically approved to treat relapsed AML
patients and the first targeted chemotherapy agent using monoclonal
Manufactured by American Home Products, gemtuzumab will be marketed
by the companys pharmaceutical division, Wyeth-Ayerst
Laboratories. We anticipate Mylotarg being an important
treatment option for older patients with relapsed CD33-positive AML
who frequently cannot tolerate conventional combination
chemotherapy, said L. Patrick Gage, phd, President,
Wyeth-Ayerst Research. Mylotarg can be administered in
outpatient settings. This may be desirable to many patients.
Accelerated Approval, Limited Studies
Gemtuzumab was approved under accelerated approval provisions. Its
safety and efficacy in AML patients with poor performance status and
organ dysfunction has not been established. Its effectiveness is
based on objective response rates. Moreover, there are no controlled
trials demonstrating a clinical benefit, such as improvement in
disease-related symptoms or increased survival, compared to any other
In three multinational phase II trials involving 142 patients,
gemtuzumab as a single agent produced a 26% overall remission rate in
patients 60 years of age and older with CD33-positive AML in first
relapse. Median duration of overall survival was 5.9 months. A 4%
incidence of severe mucositis was observed. Hair loss, a common side
effect of cancer chemotherapy, was not associated with treatment,
which is consistent with its targeted design.
Potential Side Effects
Gemtuzumab should be administered under the supervision of a
physician experienced in cancer chemotherapeutic agents. Severe
myelosuppression occurs when used at recommended doses. The most
commonly reported adverse events associated with gemtuzumab therapy
are fever, chills, nausea, vomiting, thrombocytopenia, neutropenia,
asthenia, diarrhea, abdominal pain, headache, stomatitis, dyspnea,
epistaxis, and hypokalemia.
Patients being treated for leukemia are at increased risk of
developing opportunistic infections and bleeding. In clinical
studies, 47% of patients have experienced anemia; 98%, severe
neutropenia; and 99%, severe thrombocytopenia. Careful hematologic
monitoring is required.
During the first 24 hours after administration, gemtuzumab can
produce a postinfusion symptom complex of fever and chills and, less
commonly, hypotension and dyspnea. Vital signs should be monitored
during infusion and for 4 hours thereafter.
Some patients given gemtuzumab have developed severe liver function
abnormalities, which were generally transient and reversible. In
light of this potential for adverse effects on the liver, caution
should be exercised when administering the drug to patients with
More About Gemtuzumab
Gemtuzumab is the first of a new class of anticancer agents developed
for antibody-targeted chemotherapy. This treatment strategy is based
on a proprietary linker technology that combines a potent
antitumor antibiotic with an antibody that binds to the CD33 antigen,
a glycoprotein commonly found on leukemic cells. This antigen is also
found on other bone marrow hematopoietic cells, but not on
pluripotent progenitor cells.
Gemtuzumab is a recombinant humanized antibody linked with a potent
antitumor antibiotic called calicheamicin, which was isolated from a
bacterium in a Texas soil sample. The antibody portion binds
specifically to the CD33 antigen, a glycoprotein commonly expressed
by myeloid leukemic cells.
This antibody was developed by investigators at Fred Hutchinson
Cancer Research Center in Seattle, and subsequently licensed to
Wyeth-Ayerst. The anti-CD33 antibody was humanized by Celltech Group.