PHOENIXA single dose of a radiolabeled anti-CD20
monoclonal antibody (MoAB), given following rituximab (Rituxan)
dosing, produced responses in two thirds of patients with relapsed or
refractory B-cell non-Hodgkins lymphoma (NHL), Gregory Wiseman,
MD, of the Mayo Clinic, said at the American Society for Therapeutic
Radiology and Oncology (ASTRO) annual meeting.
Rituxan was approved by the FDA in November 1997 for the treatment of
relapsed or refractory low-grade or follicular CD20-positive B-cell
non-Hodgkins lymphoma. It is an immunologically active,
chimeric monoclonal antibody that targets the CD20 antigen on mature
normal and malignant B cells.
The CD20 antigen found in lymph-oma cells is expressed only on
B cells, Dr. Wiseman said, and it does not shed,
internalize, or modulate, which is important for tumor targeting.
The investigational radioimmunother-apy agent, IDEC-Y2B8, is a murine
mo-noclonal antibody tightly conjugated to the radioisotope
yttrium-90. It also targets CD20, enabling the targeted delivery of
radiation directly to B-cell tumors.
In this phase I/II trial, three dose levels of IDEC-Y2B80.2,
0.3, and 0.4 mCi/kgwere evaluated in 51 patients with relapsed,
refractory, low- or intermediate-grade non-Hodgkins lymphoma.
Those with low-grade disease had to have failed at least two
prior treatment regimens or an anthracycline-based regimen, Dr.
Complete responses required a reduction in size of diseased lymph
nodes to not more than 1 cm × 1 cmthe same standard used
for the approval of Rituxan.
In the pivotal trials of Rituxan, the overall response rate was 48%.
In this trial using both the labeled and unlabeled antibody, the
overall response rate was 67% across all dose levels, with a complete
response rate of 25%, he said.
Patients with low-grade or follicular disease had an overall response
rate of 82% (28/34) across all dose levels, with 9 (27%) complete
responders. Of the 28 responders, 14 are still in remission and
continue to be followed. Of those who received 0.4 mCi/kg, the dose
that will be used in pivotal phase III trials, 17 of 21 patients
Patients with intermediate-grade lymphoma had an overall response
rate of 43% (6/14), with a complete response rate of 29% (4/14).
There were no responses to treatment in three patients with mantle
In answer to a question, Dr. Wiseman said that giving the unlabeled
antibody prior to the radiolabeled antibody seems to increase
the uptake of the radiolabeled antibody into the tumor.
Treatment Well Tolerated
The treatment was well tolerated, Dr. Wiseman said. Toxicity was
primarily hematologic (thrombocytopenia, neutropenia, and anemia) and
was transient and reversible, with a median recovery time of 7 to 8 days.
There was no major organ toxicity. In all patients, normal organs,
including the red marrow, received radiation doses well below the
safety limits prescribed in the clinical protocol.
Human antimouse or antichimeric antibody (HAMA/HACA) reactions
occurred in only 2% of patients and were not a therapy-limiting factor.
Phase III Trial
IDEC Pharmaceuticals is currently conducting a randomized, controlled
phase III pivotal trial comparing IDEC-Y2B8/Rituxan with Rituxan
alone in patients with low-grade or follicular non-Hodgkins
lymphoma. The trial is being performed at more than 35 sites
throughout the United States.
In this trial, IDEC-Y2B8 is administered in an outpatient setting and
does not require isolation of patients following treatment. The
entire IDEC-Y2B8/Rituxan regimen is completed in 8 days. Patients
treated with Rituxan alone receive four infusions on an outpatient
basis over a 22-day period.