ROCHESTER, MinnesotaMore than half of follicular
non-Hodgkin’s lymphoma (NHL) patients who progress after rituximab (Rituxan)
treatment respond to the experimental drug ibritumomab tiuxetan (Zevalin),
according to a multicenter clinical trial. Although most of the study’s 54
patients had only partial remissions after treatment with ibritumomab tiuxetan,
their response continued for at least 8 months. In some cases, remissions have
lasted up to 2 years.
Ibritumomab tiuxetan is the monoclonal antibody rituximab used
in conjunction with the radioactive isotope yttrium 90. Although the FDA
approved rituximab, trials on ibritumomab tiuxetan for submission to the FDA
"The study helps show that using Zevalinadding a
radioactive particle to the monoclonal antibody rituximabdoes improve
response rate," said lead investigator Thomas E. Witzig, MD, hematologist
and internist at the Mayo Clinic in Rochester, Minnesota.
Although 59% of follicular NHL patients had confirmed complete
or partial remissions according to a Lymphoma Expert Confirmation of Response
(LEXCOR) panel, objective response rates using the International NHL Response
Criteria were as high as 74%, Dr. Witzig reported.
Studies of rituximab alone show that the response rate in
relapsed low- grade NHL patients is 50%. A 1999 study of ibritumomab tiuxetan
produced response rates of 82% among NHL patients. "These studies raised
the question of whether or not the radiolabeled conjugate yttrium 90 could be
increasing efficacy when added to the monoclonal antibody rituximab," Dr.
Response and Duration
The current trial compared response rates and duration of
response on ibritumomab tiuxetan vs rituximab and prior chemotherapy
treatments. Patients in the study were a median of 54 years old and 32% had
bone marrow involvement. Seventy-four percent of patients had significant bulky
disease and half were classified as having intermediate- to high-risk disease.
Patients must have had no response to prior rituximab treatment, or a partial
or complete response that lasted less than 6 months.
The duration of response on ibritumomab tiuxetan was at least
7.7 months, though the median had not yet been reached by the end of the trial.
Those who progressed after ibritumomab tiuxetan treatment did so after a median
of more than 9 months.
The investigators also asked another important question. How
did patients who had responded to rituximab for a short time do after
ibritumomab tiuxetan treatment? Study data showed that 31% of patients had a
short partial or complete remission after rituximab treatment. Among responders
to rituximab, 76% had partial or complete remissions on ibritumomab tiuxetan.
Not surprisingly, those who did not respond to rituximab had a response rate to
ibritumomab tiuxetan of just 51%.
Those who had remissions on rituximab also had 8+ months
duration of response to ibritumomab tiuxetan, though the median had not been
reached by the end of the trial. These same patients, however, had a median
response rate of just 4 months on rituximab.
Ibritumomab tiuxetan also measured up to the patients’
previous chemotherapy treatment in this study.
Patients had been heavily pretreated with a median of four
prior regimens. Sixty-six percent had responded to their last chemotherapy
treatment, compared to the 59% remission rate with ibritumomab tiuxetan, a
difference that was not statistically significant, Dr. Witzig said. "We
know now that Zevalin was just as good as these patients’ last chemotherapy
sessions," he added.
Patients who were responders to chemotherapy were also more
successful on ibritumomab tiuxetan. Those who had remissions with chemotherapy
had a 65% response rate on ibritumomab tiuxetan and those who were resistant to
chemotherapy had a 47% ibritumomab tiuxetan response rate.
Of those who responded to chemotherapy, the duration of
response was 5 months, while this same group of patients had a response rate of
6 months on ibritumomab tiuxetan.
Most of the side effects of the Zevalin treatment were
hematologic, transient, and reversible, Dr. Witzig said. There was no liver,
lung, or kidney toxicity, and only 7% of patients required hospitalization for
infection. One patient developed human antibodies to the murine antibody
Hemoglobin and platelet counts of patients reached a nadir at 7
to 8 weeks and took 1 to 2 weeks longer to recover. "We can conclude from
this data that Zevalin is safe and effective in patients who fail
rituximab," Dr. Witzig said.