In a study of previously untreated patients
with lowgrade or follicular non-Hodgkins lymphoma (NHL), all
patients responded to the combination of tositumomab and iodine I 131
tositumomab (Bexxar) and fludarabine (Fludara). When compared to
initial treatment with fludarabine alone, the addition of Bexxar to
fludarabine increased the rate of complete response fivefold, with
the rate of complete response continuing to increase over time.
These interim results, the first to report on the combination of a
radioimmunoconjugated monoclonal antibody with standard-dose
chemotherapy in lymphoma, were presented at the 41st annual American
Society of Hematology (ASH) meeting in New Orleans.
Bexxar consists of a radioisotope (iodine-131) combined with a
monoclonal antibody. The monoclonal antibody attaches to a protein
found only on the surface of B-cells, inhibiting tumor cells directly
and/or recruiting the immune system to kill these cells.
Simultaneously, the radioisotope delivers targeted, powerful
radiation to destroy the cancer. As a result, the tumor cells receive
a greater concentration of the therapeutic radiation, while radiation
to normal tissues is minimized.
This phase II study, conducted at the Center for Lymphoma and Myeloma
at the Weill Medical College of Cornell University and New
York-Presbyterian Hospital, was designed to evaluate the safety and
efficacy of a sequential regimen of fludarabine followed by Bexxar. A
total of 38 patients with previously untreated low-grade or
follicular NHL received three cycles of fludarabine (25 mg/m²
× 5 d every 5 weeks) followed, 6 to 8 weeks later, by Bexxar.
Interim Data Show Promising Results
At least 6 months after treatment with Bexxar, 14 of the 38 patients
were evaluable for response. Of the 14 patients, 13 (93%) had stage
IV NHL at the time of treatment and 1 patient had stage II NHL. All
14 patients responded to treatment with fludarabine followed by
Bexxar. Following initial treatment with fludarabine, two patients
(14%) experienced a complete response. At the 13th week, following
treatment with Bexxar, the rate of complete response increased to 43%
(six patients). At approximately 6 months, 71% of the patients (10
patients) exhibited complete responses.
The combination of fludarabine plus Bexxar was well tolerated. The
principal side effects were hematologic, including a decrease in
blood counts, which was reversible. Nonhematologic side effects of
Bexxar were mild to moderate and included nausea, fatigue, headache,
and rhinitis. Due to the immunosuppressive effect of fludarabine,
only one patient developed a human antimouse antibody (HAMA) reaction.
Were extremely excited by these preliminary results,
which not only show a high rate of response, but also a dramatic
increase in complete response over time when these low-grade or
follicular non-Hodgkins lymphoma patients are treated with the
sequential combination of Bexxar following fludarabine, said
John P. Leonard, MD, assistant professor of medicine in the Division
of Hematology and Medical Oncology at the Weill Medical College of
Cornell University. Bexxar not only demonstrates durable
responses as a stand-alone first-line treatment in previously
untreated patients and in those whove relapsed or become
refractory, but now shows clinical potential when used in conjunction
with conventional chemotherapy as an initial treatment regimen.
Helping patients achieve long, durable complete responses is
our best hope until we find a cure for low-grade non-Hodgkins
lymphoma. This study suggests that use of Bexxar with chemotherapy is
a promising, well-tolerated combination that may offer this patient
population a much-needed new treatment option, said Dr.
Multicenter studies using Bexxar in combination with fludarabine are
scheduled to begin in 2000.