Phase 3 TOURMALINE-MM2 Study Fails to Meet Primary Endpoint in Treating Newly Diagnosed Multiple Myeloma

The phase 3 TOURMALINE-MM2 study — designed to evaluate Ninlaro (ixazomib) in combination with Revlimid (lenalidomide) and dexamethasone in patients with newly diagnosed multiple myeloma not eligible for autologous stem cell transplant — failed to meet its primary endpoint of improving progression-free survival (PFS), compared with Revlimid and dexamethasone plus placebo, according to Takeda, the company that manufactures the drug.

“There is a specific need in newly diagnosed multiple myeloma, given there are currently no approved all-oral, proteasome inhibitor-based treatment options,” lead study author Dr. Thierry Facon, of Lille University Hospital in France, said in a company-issued press release. “Findings from the TOURMALINE-MM2 trial are important overall for this patient population as well as across multiple subgroups including patients with high-risk cytogenetics. We hope these data will help inform future research and further progress for the multiple myeloma community.”

The data, which were presented at the virtual scientific meeting of the Society of Hematologic Oncology, demonstrated that the addition of Ninlaro to Revlimid and dexamethasone led to a 13.5-month increase in median PFS, compared with placebo. However, the data failed to meet the threshold for statistical significance which, according to the release, indicated that the primary endpoint was not met.

After a median follow-up of 57.8 months in the Ninlaro group and 58.6 months in the placebo group, a median PFS was not reached. Patients who received Ninlaro achieved a complete response rate of 26% versus 14% with placebo. Additionally, patients in the Ninlaro group (45.8 months) achieved a longer median time-to-progression than those in the placebo group (26.8 months).

Patients who received Ninlaro (88.1%) were more likely to experience serious or severe treatment-emergent side effects compared with those who received placebo (81.4%).

“Insights from studies like TOURMALINE-MM2 are important, especially to those patients who may benefit from the convenience of treatment options that can be taken at home,” Paul Giusti, president and CEO of Multiple Myeloma Research Foundation, said in the release. “These critical learnings enable the community to comprehensively assess the different treatment combinations available for patients and physicians.”

Currently in more than 65 countries, Ninlaro is approved in combination with Revlimid and dexamethasone to treat patients with multiple myeloma who have received at least one prior therapy. However, Ninlaro is not yet approved to treat newly diagnosed multiple myeloma.

“We hope the findings from the TOURMALINE-MM2 trial will encourage constructive conversations and help progress future research efforts, particularly for patients who could benefit from an all-oral, proteasome inhibitor-based combination that helps preserve quality of life,” Christopher Arendt, head of Takeda’s Oncology Therapeutic Area Unit, said in the release. “As a company, we remain committed to the multiple myeloma community and look forward to sharing mature data from our ongoing phase 3 multiple myeloma maintenance studies in the future.”