Gazyva (obinutuzumab) with Revlimid (lenalidomide) — a combination called Galen — is a potentially safe and effective treatment for relapsed or refractory follicular lymphoma, with over 60% of patients responding to treatment, according to the results of a Phase 1b study.
The trial’s results, “An open-label, phase Ib study of obinutuzumab plus lenalidomide in relapsed/refractory follicular B-cell lymphoma,” were published in the journal Blood.
Gazyva, developed by Roche to treat people with follicular lymphoma — the most common type of slow-growing non-Hodgkin’s lymphoma — is an antibody that targets the CD20 protein found on the surface of certain immune cells called B-cells.
Gazyva has been approved for the treatment of follicular lymphoma patients who have not been treated before or who have failed to respond to previous treatment, such as Rituxan (rituximab) — another antibody against CD20 that was developed by Roche.
While Rituxan and Gazyva work through similar processes, preclinical studies showed that Gazyva induces greater antibody-dependent cellular toxicity and direct B-cell killing effects than Rituxan.
Previous studies have shown that the addition of Revlimid — an immunotherapy that restores the function of immune cells and improves antibody-dependent cellular toxicity — to Rituxan led to greater anti-cancer effects in relapsed or refractory non-Hodgkin’s lymphomas.
These findings suggest that the combination of Gazyva with Revlimid may promote even greater therapeutic effects than the Rituxan-Revlimid combination in these patients.
A multicenter, open-label, Phase 1b/2 study (NCT01582776), sponsored by The Lymphoma Academic Research Organization, is evaluating the safety and effectiveness of Galen therapy in patients with follicular lymphoma who failed prior lines of therapy.
The primary goal of the Phase 1b part of the trial was to assess the appropriate dose of Revlimid to be administered in combination with Gazyva in the Phase 2 part of the study. Secondary goals included the combo’s safety and effectiveness in follicular lymphoma patients.
The study included 19 adults with follicular lymphoma (mean age of 61.5) who relapsed or did not respond to at least one previous line of treatment that included Rituxan. They were recruited in seven centers in France from October 2012 to January 2014.
Most patients were at an advanced stage of the disease, and eight patients were refractory to Rituxan.
Participants were assigned to receive 10 mg, 15 mg, 20 mg, or 25 mg of daily oral Revlimid in combination with Gazyva at a fixed dose of 1,000 mg for six months.
All patients had at least one adverse event, with constipation (52.6%), neutropenia — low levels of neutrophils, a type of white blood cell — (47.4%), and lack of energy and strength (36.8%) being the most common. Most of the adverse events associated with the Galen therapy were mild to moderate in nature.
Considering the occurrence of severe to very severe neutropenia after the second cycle of 25 mg of Revlimid, the toxicity review committee decided that 20 mg of Revlimid was the appropriate dose to be used in the second part of the study.
At the end of the six month-treatment, 12 patients (63.2%) responded to Galen therapy, eight patients showed a complete response, three had unconfirmed complete response, and one had a partial response.
After three years of follow-up, 73.3% of patients were alive and 52.1% of all patients showed no signs of cancer progression.
The results showed that Galen therapy was well tolerated and effective in patients with relapsed or refractory follicular lymphoma.
According to the researchers, the Gazyva-Revlimid combo therapy may be equally or even more efficient than Rituxan-Revlimid combo in follicular lymphoma patients.
Currently, the Phase 2 part of the study is assessing the effectiveness of 20 mg of Revlimid and 1,000 mg of Gazyva over six months, followed by two years of treatment maintenance, in patients with relapsed or refractory aggressive lymphoma or follicular lymphoma, or untreated follicular lymphoma.