Interim Results From REFLECT Show No New Safety Concerns for Biosimilar Rituximab, Rixathon

While Sandoz has indicated that it no longer plans to pursue regulatory approval of its biosimilar rituximab, Rixathon, in the United States, the product is approved in Europe, Japan, Australia, and New Zealand for all indications of its reference. The biosimilar has been studied in rheumatoid arthritis and in follicular lymphoma to support regulatory approval, and it is now being assessed in its first postapproval study in diffuse large B-cell lymphoma (DLBCL).

During last week’s 24th Congress of the European Hematology Association (EHA), held from June 13-16 in Amsterdam, the Netherlands, researchers presented their interim safety results from the REFLECT study, a prospective, noninterventional, observational, multicenter, open-label study of the biosimilar as a curative therapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in patients with previously untreated CD20-positive DLBCL. The study’s primary end point is complete response rate, and data are collected at baseline and every study visit for 12 months to measure efficacy and until 30 days after the last dose of rituximab to evaluate safety.

The data reported at EHA reported on safety up to September 2018, when recruitment was approximately 50% complete. The interim full analysis set included 80 patients who had a mean (SD) time from diagnosis to start of treatment of 1.5 (5.1) months. The most commonly reported baseline symptoms were enlarged lymph nodes and disease-related pain.

In total, 53 patients reported adverse events (AEs), and 19 patients had serious AEs. Treatment-related AEs were reported in 13 patients. The most frequent AEs were polyneuropathy in 10 patients, anemia in 8 patients, and fatigue in 8 patients.

These first real-world safety data for the biosimilar rituximab with CHOP in CD20-positive DLBCL were as expected, according to the researchers.

In an interview with The Center for Biosimilars^®, lead author Manfred Welslau, MD, Onkologie Aschaffenburg, Germany, said that that it is important to continue to gather data on the biosimilar in this indication because there remain concerns among practitioners about using the biosimilar in DLBCL, given the fact that patients with this disease have high rates of recurrence and rituximab is used with curative intent.

“Acceptance in noncurative situations is quite high now,” said Welslau of his peers’ attitudes toward the biosimilar, but “acceptance in curative situations is pending. I think the RELFECT study is a good way to get more acceptance into this population.”

Welslau added that, given the fact that the cost of the biosimilar is approximately 25% lower than the reference in Germany, the biosimilar has allowed the healthcare system to “keep an open space” for innovative therapies, and greater acceptance will allow for greater savings and budgetary headroom for the care of patients in Europe.

Reference

Welslau M, Marschner N, Wolff T, Otremba B, Topaly J, da Silva LB. Sandoz rituximab for the treatment of diffuse large B-cell lymphoma: interim safety results of the prospective non-interventional, observational, multicenter, open-label REFLECT study. Presented at: 24th European Hematology Association Congress; June 13-16, 2019; Amsterdam, the Netherlands. Abstract PS1074.