ORLANDO--Final results of a phase III trial show that monotherapy with
IDEC-C2B8, a new chimeric monoclonal antibody being developed by IDEC Pharmaceuticals
and Genentech, pro-duces favorable response rates in patients with relapsed
low-grade or follicular non-Hodgkin's lymphoma (NHL).
The results were reported by Peter McLaughlin, MD, of M.D. Anderson
Cancer Center, Myron Czuczman, MD, of Roswell Park Cancer Institute, and
their colleagues, in two poster presentations at the 38th Annual Meeting
of the American Society of Hematology (ASH).
Another phase II study presented at the ASH meeting demonstrates that
the addition of IDEC-C2B8 to CHOP (cyclophosphamide, doxorubicin, Oncovin,
and prednisone) chemotherapy is at least as effective as CHOP alone in
patients with newly diagnosed or relapsed low-grade or follicular lymphoma,
and produces no significant additional toxicity.
In addition, Dr. Czuczman said, the combination appears to clear minimal
residual disease in blood and marrow, which has not been demonstrated by
CHOP chemotherapy alone.
Phase III Trial Results
The phase III, open-label trial involved 166 patients with relapsed
low-grade or follicular lymphoma who were treated with single-agent IDEC-C2B8
(375 mg/m² weekly for four infusions) on an outpatient basis at 30
medical centers in the United States and Canada.
Half of the evaluable patients (76/151) responded to the MoAb. Of the
76 responses, nine (6%) were complete and 67 (44%) were partial. These
patients had either proved unresponsive to previous treatment or had experienced
up to four relapses after prior therapy, including autologous bone marrow
transplantation (BMT), Dr. Czuczman told Oncology News International in
At a median follow-up of more than 9 months after IDEC-C2B8 therapy,
the median time to progression has not yet been reached, and 70% of the
responding patients are still in remission, he said.
The most common side effects of the MoAb were mild, reversible flu-like
symptoms (fever, chills, nausea, and headache). These adverse effects occurred
primarily during the first infusion and decreased markedly in frequency
during subsequent infusions.
The chimeric antibody, which binds a mouse component to a human IgG1
backbone, showed low immunogenicity, Dr. Czuczman said. Only 1 of 166 patients
had a "clinically insignificant" elevation of human antichimeric
antibody (HACA). "Because patients don't mount a HACA response, they
could potentially be re-treated with the antibody," he said.
MoAb Has Multiple Mechanisms of Action
Unlike most MoAbs, IDEC-C2B8 has therapeutic activity in its own right
IDEC-C2B8 binds selectively to the CD20 antigen, a protein found on
Once bound to the CD20 antigen, the MoAb activates both circulating
This antibody may have other properties in addition to its immune response
Clearance of Tumor Marker
The presence of bcl-2, considered to be a marker of minimal residual
disease, in the peripheral blood and bone marrow was assessed by polymerase
chain reaction (PCR) before and after single-agent IDEC-C2B8 therapy.
More than 70% of patients whose peripheral blood was positive for bcl-2
at baseline became negative after therapy. Similarly, more than 50% of
patients whose bone marrow was positive for bcl-2 at baseline reverted
Dr. Czuczman noted that IDEC-C2B8 therapy cleared the peripheral blood
and bone marrow of bcl-2 not only in responding patients but also in some
patients who did not exhibit a "nodal" response. This raises
the possibility that the MoAb "could accomplish in vivo purging of
lymphoma cells in those compartments," he said. "It would allow
you to collect and store bcl-2-negative blood or marrow, which could potentially
be used in the future for transplantation."
IDEC-C2B8, CHOP Combination
Dr. Czuczman and his colleagues also studied IDEC-C2B8 in combination
with CHOP chemotherapy in 38 patients with low-grade or follicular lymphoma,
most of whom were previously untreated. In this phase II open-label trial,
patients received six doses of 375 mg/m² of IDEC-C2B8 intravenously
plus standard doses of CHOP every 3 weeks for six cycles.
"The overall response rate with combination therapy was at least
as good as has been described with CHOP alone," Dr. Czuczman said.
Approximately 60% of patients experienced a complete response, and 37%
had a partial response.
Researchers at Roswell Park also conducted PCR testing before and after
therapy in 20 patients. In seven of the eight patients who were bcl-2 positive
at baseline, the tumor marker was no longer present in peripheral blood
and/or bone marrow after therapy with the combination regimen.
"The conversion of the baseline bcl-2 to PCR-negativity in the
blood and marrow suggests clearing of residual disease, not previously
demonstrated with CHOP chemotherapy alone," Dr. Czuczman said.
The overall toxicity profile of the MoAb-CHOP combination was similar
to that of CHOP alone. Most of the toxic effects consisted of grade 1 or
2 reactions, Dr. Czuczman said. The overall incidence of grade 3 or 4 toxicity
was approximately 17%, he added, and these adverse events were felt to
be associated primarily with CHOP chemotherapy. No HACA reactions were