Ninlaro Found to Be Effective and Safe for Treatment of Newly Diagnosed Multiple Myeloma

In addition to improving progression-free survival (PFS) in patients with multiple myeloma who have undergone an autologous stem cell transplant, Ninlaro (ixazomib) is also well-tolerated, with low-grade, manageable side effects, according to results of the TOURMALINE-MM3 study.

After earlier phase 3 results of the TOURMALINE-MM1 study led to the approval of Ninlaro in combination with Revlimid (lenalidomide) and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy, the safety and efficacy of the oral proteasome inhibitor were further studied in the TOURMALINE-MM3 trial.

Using the findings from this study, researchers then published additional safety data in the Annals of Hematology, focusing on adverse event (AE) management recommendations for clinical practice, which doctors can use to help patients adhere to treatment and maintain their quality of life.

In the MM3 study, 656 patients were randomized 3:2 to receive either oral Ninlaro at a dose of 3 mg (395 patients) or placebo (261 patients) on days one, eight and 15 in 28-day cycles. If the drug was found to be tolerable, the dosage was increased to 4 mg at cycle five and continued up to 26 cycles (around 2 years) or until disease progression or unacceptable toxicity.

Measuring PFS, which is the time from treatment to disease worsening, was the main goal of the study. Assessing safety was another goal.

At a median follow-up of 30.9 months in the Ninlaro arm and 31.1 months in the placebo arm, 97% of patients experienced AEs of any severity, including thrombocytopenia, neutropenia, gastrointestinal toxicities, peripheral neuropathy, thromboembolic events, pneumonia, and herpes zoster.

While the rate of serious or severe AEs was higher in the Ninlaro arm compared to the placebo arm (19% versus 5%), the rate of treatment discontinuation due to AEs was similar between both arms (7% for Ninlaro versus 5% for placebo).

The most frequently reported AEs in the Ninlaro arm were nausea, diarrhea, and vomiting, which researchers noted were expected and consistent with previous studies evaluating the drug. The overall rates of AEs of clinical interest were higher in the treatment arm than in placebo, as seen with:

• nausea (in 39% of the Ninlaro arm versus 15% in the placebo arm),
• vomiting (27% versus 11%),
• diarrhea (35% versus 24%),
• thrombocytopenia (13% versus 3%), and
• peripheral neuropathy (19% versus 15%)

According to the study, the majority of AEs experienced were low-grade, non-serious, manageable with supportive therapy or dose reduction, and did not result in cumulative or long-term/late-onset toxicity. The researchers also noted that the AEs were reversible, and did not result in discontinuation, leading them to conclude that single-agent Ninlaro is a safe and effective option for this newly diagnosed patient population.