SEATTLEA new chemotherapy agent called CMA-676 that
specifically targets tumor cells led to remissions in 34% of patients
with acute myeloid leukemia (AML) in relapse and was well tolerated.
Eric Sievers, MD, of the Fred Hutchinson Cancer Research Center
reported the results of the phase II trial at the ASH meeting.
Recently named gemtuzumab zogamicin, CMA-676 is a conjugate of an
anti-CD33 antibody and the cytotoxic agent, calicheamicin. The
antibody component causes the drug to bind to AML tumor cells, which
express CD33. The calicheamicin component then kills the tumor cells,
while not harming normal blood stem cells, which do not bear CD33 molecules.
The phase II clinical trial of CMA-676 enrolled 59 patients who had
AML and were in their first relapse after a remission of at least 6
months. The subjects had received a variety of treatments before
entering the study, although none had a transplant. The patients were
given a 2-hour infusion of CMA-676 at a dose of 9 mg/m² ,which
was repeated 2 weeks later.
Twenty of the 59 patients had a remission (defined as less than 5%
blasts in the marrow, 1,500/mcL neutrophils, and no need for platelet
transfusion). Of these 20, 12 then had a bone marrow transplant, and
3 underwent chemotherapy. As of March 1999, 12 patients were still in
remission, with a median follow-up of 238 days. Of these 12, 2 had no
further treatment, 2 had chemotherapy, and 8 had bone marrow transplants.
In the question and answer period, Dr. Sievers noted
patients leukemia was either exquisitely sensitive or
unresponsive to the drug, with few responses in between.
As might be anticipated with an agent targeted to an antigen
expressed by normal myeloid precursors, hematological adverse effects
were common. Most patients had fever, chills, and grade 4
neutropenia. Most needed to be hospitalized, usually for fever and
neutropenia. Eight patients had grade 4 increases in bilirubin that
were typically reversible. Severe bone pain, seizures, diabetes
insipidus, and intracerebral bleeding were observed in individual
patients. There were no renal, gastrointestinal, or cardiac toxicities.
Although some of these side effects were significant, they were
comparably less severe than the adverse effects of standard AML
chemotherapy drugs. Dr. Sievers concluded that CMA-676 was reasonably
well tolerated and had an acceptable safety profile.
In addition to the Fred Hutchinson Cancer Research Center, the study
was conducted at the University of Chicago, the M.D. Anderson Cancer
Center in Houston, the University of Pennsylvania Cancer Center in
Philadelphia, the University of Michigan in Ann Arbor, the Hopital
Maisonneuve-Rosemont in Montreal, the University of Nebraska in
Omaha, the City of Hope National Medical Center in Duarte,
California, the University of Maryland in College Park, the
University of Miami, Princess Margaret Hospital in Toronto, Canada,
and Wyeth-Ayerst Research in Radnor, Pennsylvania.