PHOENIXA single dose of a radiolabeled anti-CD20 monoclonal antibody (MoAB), given following rituximab(Drug information on 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. Wiseman said.
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 (81%) responded.
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 cell disease.
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.