The European Commission has approved Bristol-Myers Squibb‘s Revlimid (lenalidomide) in combination with rituximab to treat adults with follicular lymphoma who are no longer responding to other therapies.
The combination is the first chemotherapy-free treatment approved in Europe for people with relapsed (returned) or refractory (resistant to treatment) follicular lymphoma.
“This approval is a significant milestone for patients with follicular lymphoma whose disease is not responding to current therapy or has returned following prior treatment,” Nadim Ahmed, president of Hematology at Bristol-Myers Squibb, said in a press release.
The decision comes after a similar recommendation by the Committee for Medicinal Products for Human Use (CHMP), issued in December. The U.S. Food and Drug Administration (FDA) had approved the combination for follicular lymphoma and marginal zone lymphoma (MZL) in May, three months after granting it priority review.
Follicular lymphoma is a subtype of non-Hodgkin’s lymphoma that initially responds to treatment. However, in most patients, cancer comes back, and periods of remission become shorter with time.
Given its incurable nature, new treatments are needed to both extend patient lives and prevent their cancer from progressing, especially in those who have been treated previously.
Rituximab (marketed under the brand names Rituxan and Truxima) is a monoclonal antibody that targets B-cells, the immune cells that cause follicular lymphoma. The agent specifically binds to immature and mature B-cells, triggering their death. It is given by injection into a vein.
Revlimid is an immunomodulator that works by boosting the immune system’s ability to find and destroy tumor cells. It stimulates an increase in the number and activation of immune T and natural killer (NK) cells, enhancing the killing of cancer cells. It is available as oral capsules.
The combination of Revlimid and rituximab (also known as R2) increases a patient’s natural immune response against cancer.
“By utilizing the patient’s own immune system, R2 represents a new approach to treatment in follicular lymphoma, giving patients a chemotherapy-free option with demonstrated efficacy,” said John Gribben, president of the European Hematology Association and Centre for Haemato-Oncology, Barts Cancer Institute, in England.
The approval was based on findings from the AUGMENT Phase 3 trial (NCT01938001), which tested the efficacy and safety of R2 in 295 people with previously treated follicular lymphoma, grade 1, 2 or 3a.
After a median follow-up of 29.2 months, participants given the combination remained alive and without cancer progression for a median of 39.4 months, more than two years longer than what was observed in patients who took rituximab plus placebo (13.8 months). This represented a 60% reduction in the risk of disease progression or death.
“In the phase 3 AUGMENT study, patients receiving R2 experienced extended periods of disease remission versus patients receiving rituximab plus placebo,” Ahmed said.
The R2 combination also increased the percentage of patients who responded to treatment (78% vs. 53%) and who achieved a complete response (34% vs. 18%), again compared to those given rituximab and placebo.
Adverse events such as low neutrophil count, diarrhea, low white blood cell count, constipation, cough, and fatigue were more common among patients treated with R2 than those treated with rituximab and placebo.
Bristol-Myers Squibb also submitted findings from the MAGNIFY Phase 3b trial (NCT01996865) to support the combo’s safety and efficacy in patients with relapsed or refractory follicular lymphoma, including those who did not respond to rituximab.