STANFORD, CaliforniaSeventy 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
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
"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.