NEW ORLEANSThe arrival of new antibody-based
radioimmunothera-pies may change the bleak prognosis for low-grade
non-Hodgkins lymphoma (NHL) that transforms to a more
In a retrospective analysis of patients with transformed low-grade
NHL, Andrew D. Zelenetz, MD, PhD, chief of the Lymphoma Service,
Department of Medicine, Memorial Sloan-Kettering Cancer Center, found
that treatment with radiolabeled tositumomab (Bexxar) produced an
overall response rate of 53%.
Median response duration from the time of treatment was 11 months
overall and 20 months in patients with a complete response. Dr.
Zelenetz presented these findings at the 41st annual meeting of the
American Society of Hematology.
The data for the analysis were drawn from three phase I to III
multicenter clinical trials plus two compassionate-use patients.
There were 59 patients, but results for one patient were too early
The majority of patients had diffuse B-cell lymphoma (see Table).
Patients were initially diagnosed with low-grade disease (small cell
lymphocytic, follicular small cleaved cell, or follicular mixed cell
with more than 50% small cleaved cell). Transformation was
demonstrated by biopsy evidence of a more aggressive histology at any
time prior to study entry.
Patients had received a median of four prior chemotherapy regimens,
and the median duration of response to the last previous chemotherapy
was 4 months. Forty-eight percent of patients had not responded to
chemotherapy. Chemotherapy had produced a complete response in 22% of
patients, with a median duration of 6 months.
Patients received a single dosimetric dose of 450 mg of tositu-momab
IV followed by 35 mg of tositumo-mab radiolabeled with 5 mCi of
iodine 131. Whole body counts were used to calculate the required
activity for delivering the desired therapeutic dose of 65 cGy for
patients with platelet counts of 100,000 to 149,999 cells/mm³
and 75 cGy for patients with platelet counts over 150,000 cells/mm³.
Patients then received a single therapeutic dose of 450 mg of
tositumomab IV followed by 35 mg of tositumomab containing the
therapeutic dose of iodine 131.
Dr. Zelenetz reported that some type of response occurred in 31 of 58
patients (53%), including complete responses in 17 patients (29%).
When the data were analyzed excluding patients with follicular
large-cell lymphoma, who are thought to have a better prognosis, the
overall response rate was 46% (12 of 46 patients), and the median
duration of response was 10 months. In this subset, the complete
response rate was 22% (10 patients), with a median response duration
of 20 months.
To determine whether patients with newly transformed disease would
respond well, the researchers analyzed overall response according to
time from disease transformation in 6-month increments. Response
ranged from 42% to 62% but was not significantly different among
cohorts and did not correlate with time since transformation.
This was a surprising result, Dr. Zelenetz said in an
interview with ONI. There was no significant difference in time
of response to treatment based on time since transformation. This is
clearly a very active therapy in patients who do poorly on other
forms of treatment, he commented.
The principal toxicity was hematologic: 19% of patients had an
absolute neutrophil count of less than 500 cells/mm³, and 4% had
platelet counts less than 10,000 cells/mm³. The nadir typically
occurred at week 5 to 6, with recovery by week 8 to 9.
These are difficult patients, but when tositumomab is approved
for clinical use, we will have a new therapy that can help them,
Dr. Zelenetz said.