Iodine I 131 Tositumomab Induces Response in 70% of Patients Progressing After Rituximab

STANFORD, California—Seventy percent of low-grade and transformed low-grade non-Hodgkin’s lymphoma (NHL) patients respond to the drug iodine I 131 tositumomab (Bexxar) even though progressing after rituximab (Rituxan). A study of 40 patients who had previously failed to respond or progressed on rituximab, also showed that 40% had a complete response or remission after treatment with iodine I 131 tositumomab.

The median duration of response was 15.4 months, though these data are still preliminary, according to lead researcher Sandra J. Horning, MD, professor of medicine, Division of Oncology and Bone Marrow Transplantation at Stanford University Medical School, California.

A radiolabeled monoclonal antibody, iodine I 131 tositumomab has been shown to be active in chemotherapy-relapsed or refractory indolent or transformed indolent NHL. The biologics license application for iodine I 131 tositumomab is currently under review by the Food and Drug Administration.

"Bexxar was effective in all patient categories, including those who were heavily pretreated," Dr. Horning said.

The confirmed overall response rate was 60%. The median estimated time of progression for responding patients was 16.8 months, though that number may grow larger as the study continues. "We recently saw one man in the study, for instance, who was celebrating his 2-year anniversary in complete remission," Dr. Horning said.

Previously Intractable Disease

Many of the patients in the study had previously intractable disease. Seventy percent had four or more prior chemotherapy treatments. Thirty-two percent had bone marrow involvement.

Sixty percent or 24 patients in the study had stable disease or progressed after being treated with rituximab. Twelve had a remission of less than 6 months, and four had a duration of response greater than 6 months on rituximab.

The 24 patients in the study who had no response to prior rituximab therapy achieved a high overall response rate of 67% and a complete response rate of 25% with iodine I 131 tositumomab.

Dr. Horning explained that previous studies have shown that indolent NHL patients achieved a 50% response rate to rituximab, and the median duration of response was about 11.6 months. Yet only 40% of rituximab patients who were previous responders respond a second time. "The majority of patients will require more therapy after rituximab," she said.

Could tositumomab provide a better outlook for these patients? The study objectives included assessing the patients’ overall response rate to iodine I 131 tositumomab, duration of response, time to progression, and overall safety of the drug.

Treatment Well Tolerated

Results from the study demonstrated that treatment with iodine I 131 tositumomab was well tolerated with predictable and reversible hematologic toxicity, Dr. Horning reported. Adverse events were predominantly grade 1 and 2. Grade 3 neutropenia occurred in 23% of patients and grade 3 thrombocytopenia in 23%. Grade 4 neutropenia occurred in 18% of patients and grade 4 thrombocytopenia in 3%.

The median recovery time from nadir to grade 2 was 8 days for neutrophils and 17 days for platelets. None of the patients in this trial developed HAMA (human antibodies to murine antibody) following the therapeutic dose.

"All in all, Bexxar provided significant response rates for these patients. We will need longer follow-up, however, to determine the final median duration of response," Dr. Horning said.

"The results of this study demonstrate that Bexxar produces durable complete responses in patients who have failed rituximab treatments," said Michael F. Bigham, former president and chief executive officer of Coulter Pharmaceutical (now Corixa, Seattle, Washington, following a merger in December 2000), the firm that produces Bexxar. "Such response rates indicate that Bexxar may soon provide NHL patients with a greatly needed new treatment option."

In a separate study, 35% of 251 patients treated with Bexxar achieved a complete response lasting a median of more than 3 years. The patients all had low-grade or transformed low-grade NHL, and included those who were previously untreated, refractory, and heavily pretreated.