ROCKVILLE, MarylandBex-xar (tositumomab and iodine I-131
tositumomab) has received FDA approval for the treatment of patients with
CD20-positive follicular non-Hodgkin’s lymphoma (NHL), with and without
transformation, whose disease is refractory to rituximab (Rituxan) and has
relapsed following chemotherapy. Bexxar will be co-marketed in the United
States by Corixa Corporation, Seattle, and GlaxoSmith-Kline, Philadelphia.
Bexxar is a dual-action therapy that pairs the
tumor-targeting ability of a cytotoxic monoclonal antibody (tositumo-mab) and
the therapeutic potential of radiation (iodine-131) with patient-specific
The efficacy of the Bexxar therapeutic regimen was shown in
a multicenter, single-arm study of 40 patients with follicular NHL whose
disease had relapsed following rituximab or had not responded to rituximab.
The results of this study were supported by demonstration of durable objective
response in four other single-arm studies, enrolling 190 patients with
rituximab-naïve, follicular NHL with or without transformation who had
relapsed following chemotherapy or were refractory to chemotherapy. In these
studies, the overall response rates ranged from 47% to 64% (median duration,
12 to 18 months), Corixa and GlaxoSmith-Kline said in a press release.
Study results for Bexxar in patients with a durable
response were recently reported at the 50th Annual Meeting of the Society of
Nuclear Medicine (SNM), held in New Orleans. An analysis of data from the five
clinical trials showed long-term durable remissions in 30% of patients with
relapsed and refractory low-grade NHL. The results were seen after just a
single treatment, with some remissions lasting up to 8 years, said Richard
Wahl, MD, chairman of nuclear medicine, Johns Hopkins Medical Institutes.
The analysis included 250 patients who participated in the
five clinical trials of NHL patients with relapsed or refractory disease. Of
these patients, 76 (30%) met the definition for durable response, ie, an
objective response lasting 12 months or longer by independent, blinded
assessment. The median follow-up for these patients was 44.6 months, although
some patients were treated as long ago as 8 years. Almost all of the durable
responders received the 75 cGy prescribed dose of Bexxar (some received 65 cGy).
For the 76 durable responders, the rate of complete
response was 76%, and median time to progression was 58.4 months. "These
results were based on a single therapeutic administration of Bexxar, and we
see response durations of 5 years. The longest response duration we’ve seen
has been more than 8 years," Dr. Wahl said.
Most of the responders had received three prior
chemotherapy regimens, and one third had received more than four; 38% had
demonstrated no response to their last treatment. Considering the challenging
patient population, and the tendency of NHL to relapse ever more frequently
and with shorter response durations with successive therapies, "these
findings are quite unexpected and exciting," Dr. Wahl said.
Using 10 prognostic factors, the investigators established
that 80% of durable responders had at least three poor-prognostic features and
30% had five or more. The beneficial effects of long-term responses,
therefore, did not result from a selection of better-prognosis patients, he
Patients were less likely to achieve a durable response if
they had a lack of response to their last chemotherapy, elevated lactate
dehydrogenase (LDH), bulky disease, and modified International Prognostic
Index (IPI) score of 3 or higher. Nonfollicular histology was also predictive
of a less favorable response, indicating that the underlying substrate is
important, he said.
In a separate retrospective analysis presented at SNM, 35
evaluable patients with rituximab-refractory disease had a 63% response rate
to Bexxar, including complete responses in 29%, according to lead investigator
Donald Podoloff, MD, of Texas Medical Center, Houston. The median duration of
response was 25 months. In complete responders, median duration has not yet
been reached at 28 months. With a follow-up of 40 months, eight patients (23%)
remain in complete remission, Dr. Podoloff said.
Patients With Thrombocytopenia
Also presented at the SNM meeting were results showing that
patients with mild thrombocytopenia can be safely and effectively treated with
Bexxar using an attenuated 65 cGy total body dose. Stanley J. Goldsmith, MD,
director of nuclear medicine, New York Presbyterian Hospital, presented the
The study evaluated this reduced dose in 190 patients with mild
thrombocytopenia at baseline (platelet counts 100,000 to 149,999/µL),
constituting 22% of the total 870 patients in the Bexxar clinical trials and
an expanded access program. While about 50% of patients receiving Bexxar at 65
cGy had hematologic toxicity, the rate of serious infections was only 3.7%,
and bleeding occurred in only 1.6%. Supportive care was required in 32% of
patients. Importantly, the attenuated dose was associated with an overall
response rate of 48% and a complete response rate of 25%; therefore, efficacy
was not compromised. The low incidence of clinical consequences of the
hematologic toxicity and the good response rates are similar to what is
observed in patients with normal platelet counts receiving the 75-cGy dose.