ASCO—Tositumomab (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 36^th 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 disease—t(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.”