New antibody shows promise in relapsed non-Hodgkin lymphoma
Last Updated: 2011-12-15 17:23:02 -0400 (Reuters Health)
By Fran Lowry
NEW YORK (Reuters Health) - A phase II trial comparing rituximab with the investigational monoclonal antibody obinutuzumab (Roche/Genentech) in patients with relapsed non-Hodgkin lymphoma (NHL) showed a trend toward more responses to the new agent, according to a presentation this week in San Diego at the 53rd annual meeting of the American Society of Hematology (ASH).
"This randomized phase II trial was performed to get an initial sense of the comparative toxicity and efficacy of this novel anti-CD20 monoclonal antibody, which is also called GA101, compared with rituximab, to see whether randomized phase III trials with this molecule were justified," lead investigator Dr. Laurie Sehn, from the University of British Columbia and the British Columbia Cancer Agency, Vancouver, BC, Canada, told Reuters Health.
Survival rates for NHL have improved significantly over the last several decades because of effective targeted therapies such as rituximab, that aim directly at the key molecular features of the disease, Dr. Sehn noted.
Obinutuzumab is the first type II bio-engineered monoclonal antibody specifically targeting the lymphoma biomarker CD20 ever studied in NHL.
"Rituximab is a type I antibody, GA101 is a type II antibody, and as a consequence, it results in a different effect on tumor cells," Dr. Sehn explained. "It has been shown in the laboratory to be more effective at directly inducing tumor cell death. Also, GA101 has been engineered to more effectively interact with the normal immune system, such that it can induce a stronger reaction of the immune system against the lymphoma cell."
For the current study, Dr. Sehn and her team enrolled 175 patients who had previously responded to rituximab. They randomly assigned patients to receive four weekly injections of either GA101 or rituximab, and they assessed response to treatment between 28 and 42 days after the last dose. In the abstract for the meeting, the researchers said most patients (149) had follicular lymphoma; the others had non-follicular indolent NHL, and the two treatment groups were "well balanced for standard prognostic features."
Patients who responded continued to receive their assigned treatment every two months for up to two years.
The researchers said at the meeting that preliminary data show GA101 yielding higher response rates than rituximab. The overall response rate for GA101 was 44.6% vs 33.3% for rituximab, and the complete remission rate in the GA101 arm was 12.2% versus 5.3% for rituximab.
The safety of the two agents has been comparable, Dr. Sehn said. Patients on GA101 have had more temporary reactions to infusion, and a higher rate of mild cough. These events were generally considered mild and did not result in significant differences in treatment discontinuation.
Nine patients in the rituximab arm and five in the GA101 arm had severe adverse events during the four-week induction period.
Besides infusion reactions, severe adverse events in the GA101 patients included neutropenia with fever, pleural effusion, and kidney stones. Infusion related reactions were seen mostly during the first infusion and decreased both in frequency and severity with subsequent infusions.
Fatigue, back pain, decreased appetite, and insomnia were also more frequent with GA101 than with rituximab.
In phase III trials already underway, GA101 is being tested as initial therapy of both indolent non-Hodgkin lymphoma and aggressive NHL in combination with chemotherapy, and compared with rituximab and chemotherapy.
Dr. Jane N. Winter, from Northwestern University Feinberg School of Medicine in Chicago, who moderated a press briefing for reporters at the ASH meeting, told Reuters Health: "This is a new antibody with differences in mechanism. It will be important to understand, if indeed it turns out to be more effective in phase III trials, why it is better, as it acts by at least three separate strategies to kill lymphoma cells."
Dr. Winter added: "This will be particularly important as it is used in other histologies, such as diffuse large B-cell lymphoma."
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