Phase 3 Study of Ixazomib in Select Multiple Myeloma Patients Reports Benefits

Takeda Pharmaceutical Co. has announced that Ninlaro (ixazomib), combined with lenalidomide and dexamethasone as a therapeutic approach for relapsed and/or refractory multiple myeloma (MM), markedly increases a patient’s progression free survival, according to the results of a Phase 3 clinical trial, published as “Oral Ixazomib, Lenalidomide, and Dexamethasone for Multiple Myeloma” in The New England Journal of Medicine.

MM is a rare form of cancer of the plasma cells, with more than 114,000 new cases reported worldwide each year. Myeloma cells highly rely on proteasome for protein recycling and production of large amounts of M-protein, an abnormal antibody that causes several of the symptoms characteristic of this disease.

Ninlaro was the first orally administered proteasome inhibitor approved by the U.S. Food and Drug Administration (FDA) to be used in combination with lenalidomide and dexamethasone for the treatment of MM patients who received at least one prior therapy. Now, researchers have shown that this combination has significant benefits in patients with relapsed and/or refractory MM, when compared to dexamethasone and lenalidomide alone.

“NEJM has published the results of the first Phase 3 study supporting an all-oral triplet regimen containing a proteasome inhibitor in multiple myeloma. With the emergence of long-term treatment as a preferred approach for multiple myeloma, it is crucial that we investigate more ways to improve treatment sustainability for patients,” the study’s first author and lead investigator, Philippe Moreau, MD, of the University of Nantes, France, said in a press release. “The TOURMALINE-MM1 [trial] results demonstrated that ixazomib in combination with lenalidomide and dexamethasone is an effective and tolerable oral regimen with a manageable safety profile for patients with relapsed and/or refractory multiple myeloma.”

The Phase 3 trial, an international, randomized, double-blind and placebo-controlled study, enrolled 722 patients with relapsed and/or refractory MM and addressed the effects of once-weekly oral administration of Ninlaro capsules plus the standard chemotherapy agents, lenalidomide and dexamethasone.

Researchers reported a clinically meaningful extension of progression-free survival of 20.6 months versus 14.7 months in the control group, receiving placebo plus standard care. All pre-specified patient subgroups, including those with poor prognosis or high-risk cytogenetic abnormalities, showed benefits from the ixazomib regimen. Frequency of serious adverse events and on-study deaths were similar among the two groups. Though limited, ixazomib showed additional toxic effects, such as rash, low gastrointestinal adverse events, and increased incidence of peripheral neurophaty.

“The publication of the Phase 3 TOURMALINE-MM1 trial results is another important milestone for patients and physicians. This reflects invaluable efforts from our researchers, the study investigators, the patients and their families,” said Dixie-Lee Esseltine, MD, FRCPC, vice president, Oncology Clinical Research, Takeda. “The publication concluded that the addition of ixazomib to lenalidomide and dexamethasone was associated with significantly longer progression-free survival; the additional toxic effects with this all-oral regimen were limited. We look forward to sharing additional ixazomib data from our ongoing TOURMALINE studies over the next few years.”

Other TOURMALINE ongoing trials are investigating ixazomib effects in combination with lenalidomide and dexamethasone in newly diagnosed MM patients, and ixazomib alone in newly diagnosed patients who have or have not undergone autologous stem cell transplant. The combination of ixazomib plus dexamethasone in relapsed or refractory systemic light-chain amyloidosis is also being compared with physician choice of selected regimens.