Ninlaro Maintenance Delays Disease Progression, Death in Myeloma Patients, Phase 3 Trial Shows

Multiple myeloma patients who receive Ninlaro (ixazomib) maintenance after responding to their initial treatment live longer without their disease worsening or returning than patients given a placebo, a Phase 3 clinical trial shows.

The TOURNALINE-MM3 trial (NCT02181413), where Ninlaro reduced the risk of disease progression or death by 28%, included patients given standard induction therapy, followed by high-dose chemotherapy and an autologous stem cell transplant.

Findings were recently presented at the 2019 Transplantation & Cellular Therapy Meetings of the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research in Houston.

The study, “Maintenance Therapy with the Oral Proteasome Inhibitor (PI) Ixazomib Significantly Prolongs Progression-Free Survival (PFS) Following Autologous Stem Cell Transplantation (ASCT) in Patients with Newly Diagnosed Multiple Myeloma (NDMM): Phase 3 Tourmaline-MM3 Trial,” was presented by Gareth Morgan, MD, from the University of Arkansas for Medical Sciences.

Ninlaro, developed by Takeda, is a proteasome inhibitor, meaning a substance that prevents the proteasome — a cellular complex that breaks down unnecessary or faulty proteins — from working normally, leading to the accumulation of toxic proteins within cells.

The treatment is approved in combination with Revlimid (lenalidomide) and dexamethasone for myeloma patients who received at least one prior treatment, but researchers believe its efficacy, safety, and once-weekly dosing would make it ideal for use as a maintenance treatment.

Because maintenance therapy after an autologous stem cell transplant can delay disease progression and prolong survival in multiple myeloma patients, Takeda and its subsidiary, Millenium Pharmaceuticals, designed TOURMALINE-MM3 to determine if Ninlaro could be used in such setting.

The double-blind trial included 656 patients who randomly received Ninlaro (395 patients) or a placebo (261 patients) after responding to their first-line treatment — induction therapy with a proteasome inhibitor or a immunosuppressive medicine, followed by high-dose chemotherapy and a stem cell transplant.

Participants, with a median age of 58 years, received the treatment once weekly, in a three-weeks-on, one-week-off schedule until their disease progressed or signs of severe toxicity were reported. Of these patients, 79% had achieved a complete response or a very good partial response to the first-line induction therapy, and 21% had had a partial response.

Patients receiving Ninlaro lived a median of 26.5 months without their disease worsening or returning, compared with 21.3 months for those on the placebo. This represented a 28% reduction in the risk of disease progression or death.

This benefit was seen across multiple patient subgroups, including those with advanced disease, those at high risk of relapse, those who had never received a prior proteasome inhibitor, and those who did.

Patients were more likely to experience a deepening in their response after receiving Ninlaro, compared with the placebo. Additionally, 12% of patients on Ninlaro who were positive for minimal residual disease (MRD) — cancer cells that remain in the blood or bone marrow after treatment — at study entry were converted to MRD-negative. For those receiving placebo, the figure was 7%.

More patients on Ninlaro experienced a serious adverse event than those on placebo — 42% versus 26% — which included infections, gastrointestinal disorders, and low levels of blood cells. However, few patients on both groups discontinued treatment due to adverse events — 7% versus 5%. One patient died on Ninlaro, but researchers did not clarify if this death was related to treatment.

“This study demonstrated a 28% reduction in the risk of progression/death with ixazomib maintenance, supporting ixazomib as a valuable option for maintenance therapy in responding patients post-ASCT,” the researchers concluded.