Bexxar Plus Fludarabine Effective First-Line Therapy for NHL

In a study of previously untreated patients with lowgrade or follicular non-Hodgkin’s lymphoma (NHL), all patients responded to the combination of tositumomab and iodine I 131 tositumomab (Bexxar) and fludarabine (Fludara). When compared to initial treatment with fludarabine alone, the addition of Bexxar to fludarabine increased the rate of complete response fivefold, with the rate of complete response continuing to increase over time.

These interim results, the first to report on the combination of a radioimmunoconjugated monoclonal antibody with standard-dose chemotherapy in lymphoma, were presented at the 41st annual American Society of Hematology (ASH) meeting in New Orleans.

Bexxar consists of a radioisotope (iodine-131) combined with a monoclonal antibody. The monoclonal antibody attaches to a protein found only on the surface of B-cells, inhibiting tumor cells directly and/or recruiting the immune system to kill these cells. Simultaneously, the radioisotope delivers targeted, powerful radiation to destroy the cancer. As a result, the tumor cells receive a greater concentration of the therapeutic radiation, while radiation to normal tissues is minimized.

This phase II study, conducted at the Center for Lymphoma and Myeloma at the Weill Medical College of Cornell University and New York-Presbyterian Hospital, was designed to evaluate the safety and efficacy of a sequential regimen of fludarabine followed by Bexxar. A total of 38 patients with previously untreated low-grade or follicular NHL received three cycles of fludarabine (25 mg/m² × 5 d every 5 weeks) followed, 6 to 8 weeks later, by Bexxar.

Interim Data Show Promising Results

At least 6 months after treatment with Bexxar, 14 of the 38 patients were evaluable for response. Of the 14 patients, 13 (93%) had stage IV NHL at the time of treatment and 1 patient had stage II NHL. All 14 patients responded to treatment with fludarabine followed by Bexxar. Following initial treatment with fludarabine, two patients (14%) experienced a complete response. At the 13th week, following treatment with Bexxar, the rate of complete response increased to 43% (six patients). At approximately 6 months, 71% of the patients (10 patients) exhibited complete responses.

The combination of fludarabine plus Bexxar was well tolerated. The principal side effects were hematologic, including a decrease in blood counts, which was reversible. Nonhematologic side effects of Bexxar were mild to moderate and included nausea, fatigue, headache, and rhinitis. Due to the immunosuppressive effect of fludarabine, only one patient developed a human antimouse antibody (HAMA) reaction.

Conclusions

“We’re extremely excited by these preliminary results, which not only show a high rate of response, but also a dramatic increase in complete response over time when these low-grade or follicular non-Hodgkin’s lymphoma patients are treated with the sequential combination of Bexxar following fludarabine,” said John P. Leonard, MD, assistant professor of medicine in the Division of Hematology and Medical Oncology at the Weill Medical College of Cornell University. “Bexxar not only demonstrates durable responses as a stand-alone first-line treatment in previously untreated patients and in those who’ve relapsed or become refractory, but now shows clinical potential when used in conjunction with conventional chemotherapy as an initial treatment regimen.”

“Helping patients achieve long, durable complete responses is our best hope until we find a cure for low-grade non-Hodgkin’s lymphoma. This study suggests that use of Bexxar with chemotherapy is a promising, well-tolerated combination that may offer this patient population a much-needed new treatment option,” said Dr. Leonard.

Multicenter studies using Bexxar in combination with fludarabine are scheduled to begin in 2000.