| Study
shows radioactive antibodies produce durable remissions of three
years or more
originally posted May 22, 2000
ANN ARBOR, MI - A radioactive antibody compound
known as Bexxar produced tumor shrinkage in 97 percent of
76 previously untreated patients with advanced-stage, low-grade
non-Hodgkins lymphoma (NHL) in a new study at the University
of Michigan Comprehensive Cancer Center.
Most notably, 76 percent of patients achieved
a complete remission, with no sign of cancer. In addition,
84 percent of patients with evidence of lymphoma at the molecular
level at the start of the trial achieved molecular remission
for as long as three years with the treatment. Molecular remissions
were determined by a rigorous use of polymerase chain reaction,
or PCR, technology, arguably the most sensitive cancer detection
method available today.
These promising results, from the first completed
study of a first-line, stand-alone radioimmunotherapy for
cancer, were presented today at the meeting of the American
Society of Clinical Oncology by Mark S. Kaminski, M.D., U-M
professor of hematology/oncology and co-director of the U-M's
leukemia/lymphoma and bone marrow transplant programs.
The original studies in the therapeutic development
of Bexxar, or Iodine I 131 tositumomab, were done at the U-M
by Kaminski and his colleague Richard Wahl, M.D., professor
of nuclear medicine and radiology. The therapy is now being
jointly developed by Coulter
Pharmaceutical, Inc. and SmithKline
Beecham.
"We are extremely excited by these findings,
which showed remarkable response rates and molecular remissions
lasting up to and beyond three years," says Kaminski.
"Molecular remissions are seldom seen with chemotherapy
in low-grade lymphoma, and appear to coincide with prolonged,
durable responses. Furthermore, these results demonstrate
the potential of this treatment as an effective and well-tolerated
first-line, single-agent treatment for low-grade lymphoma,
a disease without a known cure."
Bexxar is a radioimmunotherapy that combines
a mouse monoclonal antibody attached to radioactive iodine
131. It attaches to a protein found only on the surface of
the blood's B-cells, including those turned malignant in non-Hodgkin's
lymphoma patients. The compound is believed to work through
a combination of immune system activity involving the monoclonal
antibody, and effects from the radiation released by the iodine
131. Through this targeted approach, the tumor cells receive
a greater concentration of therapeutic radiation while minimizing
radiation exposure to normal tissues.
The Phase II study, conducted entirely at the
U-M, enrolled 76 patients with previously untreated, advanced-stage,
low-grade follicular lymphoma. The study was designed to evaluate
the safety and efficacy of Bexxar as an NHL treatment given
by itself and as the first treatment approach.
Patients received a trace dose, followed one
to two weeks later with a therapeutic dose. No further treatment
was given. This is in contrast with what patients would have
experienced if given chemotherapy treatment, which is commonly
repeated every three to four weeks for several months.
Patients tolerated Bexxar treatment well. Moderate,
reversible low blood counts were seen, but no patients required
hematologic supportive care. Sixty-two percent of patients
developed human anti-mouse antibodies (HAMA). About two thirds
of these patients experienced flu-like symptoms lasting less
than one week.
Virtually all patients - 74 of 76 - responded
in some way to treatment. An impressive number of patients
(58) achieved a complete response. About 70 percent of those
patients are projected to continue to be disease-free for
at least three years.
PCR analyses were conducted to test for detectable
signs of disease in bone marrow among all patients before
and after therapy. Of the 37 patients who had molecular signs
of the cancer before treatment, 31 achieved molecular remissions
when measured again later. About 75 percent of such patients
are projected to avoid relapse o f their disease for at least
three years.
A remission usually measures a patient's disease-free
status based on the absence of disease signs in examination
and medical imaging. But molecular remissions are based on
tests at the DNA level to see if the disease has been eradicated.
The PCR assay can detect one cancerous cell among a million
normal cells; in non-Hodgkin's lymphoma the test looks for
aberrant cells in the bone marrow and blood and can demonstrate
how completely the disease has been destroyed by treatment.
Non-Hodgkin's lymphoma is a form of cancer that
affects the blood and lymphatic tissues. The sixth leading
cause of cancer death in the U.S., NHL also has the second
fastest-growing incidence rate of all cancers.
According to the National Cancer Institute,
nearly 300,000 Americans have NHL, among them 140,000 with
the low-grade or transformed low-grade forms of the disease.
In more than 30 years, the survival rates of low-grade NHL
patients have not changed, and patients continue to die from
the disease or complications associated with current treatments.
The study was funded by Coulter Pharmaceutical.
The clinical trial at the U-M is currently
closed, but prospective patients and their families may find
out more from Coulter Pharmaceutical by calling 800-823-7003.
Open clinical trials at U-M can be searched
online.
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