ASCOTositumomab (Bexxar), an investigational antibody-based
radioim-munotherapy agent, has been shown to be effective as
first-line treatment of advanced-stage, low-grade follicular
lymphoma, Mark Kaminski, MD, said at the 36th Annual
Meeting of the American Society of Clinical Oncology, New Orleans.
The study was conducted at the University of Michigan Comprehensive
Cancer Center, where Dr. Kaminski is professor of hematology/oncology
and director of the leukemia/lymphoma program.
The phase II study enrolled 76 patients with previously untreated
stage III/IV CD20+ follicular lymphoma. Virtually all of the patients
(74 of 76, 97%) responded to treatment, and 58 patients (76%) had a
complete response. In addition, 84% of patients with evidence of
lymphoma at the molecular level at the start of the trial achieved
molecular remissions, some lasting as long as 3 years.
We
are extremely excited by these findings, which showed remarkable
response rates and molecular remissions ongoing beyond 3 years,
Dr. Kamin-ski said. Molecular remissions are seldom seen with
chemotherapy in low-grade lymphoma, and appear to coincide with
prolonged, durable responses, he added.
Furthermore, he noted, these results demonstrate the potential
of this treatment to change the prognosis for patients with low-grade
lymphoma, a disease without a known cure.
Patients had either follicular small-cleaved-cell lymphoma (71%) or
follicular mixed-cell lymphoma (29%), and the majority (70%) had
stage IV disease.
Patients first received a single intravenous dosimetric dose of 450
mg of unlabeled tositumomab, followed by 35 mg of tositumomab
radiolabeled with 5 mCi of iodine 131. Whole body gamma counts were
used to determine the radioactive clearance. These data were then
used to calculate a patient-specific therapeutic dose designed to
deliver 75 cGy to the whole body. The therapeutic dose was
administered on day 7; patients again received an infusion of
unlabeled antibody, followed by tositumomab containing the
therapeutic dose of iodine 131.
Molecular Remissions
Polymerase chain reaction (PCR) analyses were conducted to test for
detectable signs of diseaset(14;18 translocation)in blood
and marrow among all patients before and every 6 months after
therapy.
Of the 37 patients who had molecular signs of lymphoma before
treatment, 31 (84%) achieved molecular remissions when measured again
later. About 60% of these patients are projected to remain in
molecular and complete remission for at least 3 years.
Patients tolerated tositumomab treatment well. Moderate, reversible
myelo-suppression was seen. Nadirs typically occurred 4 to 7 weeks
after therapy. Grade 4 neutropenia occurred in 5% of patients, and no
grade 4 thrombocytopenia was noted. No patients required hematologic
supportive care.
Sixty-two percent of patients developed human antimouse antibodies
(HAMA) in a median of 38 days, with 41% of patients developing HAMA
within 13 days. Of those patients seroconver-ting within the first 2
weeks of therapy, about two thirds experienced flu-like symptoms
clearly associated with HAMA, which resolved in a few days.
A single treatment with iodine 131 tositumomab is highly
effective as first-line therapy for follicular lymphoma and results
in durable clinical and molecular remissions, Dr. Kaminski
concluded.
In more than 30 years, he noted, the survival rates of low-grade
lymphoma patients have not changed when standard chemotherapy has
been used. This trial produced a 97% response rate and superior
progression-free survival of 59% at 3 years. These results strongly
suggest we have a highly effective new therapy that can help these
patients early in the course of this indolent disease.