TOURMALINE — new gem unearthed in the MM treatment landscape

Over the past 15 years, proteasome inhibitors have been incorporated in the treatment armamentarium for multiple myeloma (MM) with promising outcomes, in particular when combined with other chemotherapeutic drugs. New data supporting these combinations are now available from the phase III TOURMALINE-MM1 trial.

In this trial, patients with relapsed and/or refractory MM received lenalidomide and dexamethasone supplemented with either the proteasome inhibitor ixazomib (n = 360) or placebo (n = 362). Median progression-free survival (PFS) in the ixazomib group was 20.6 months versus 14.7 months for the placebo group (P = 0.01). In patients with high-risk cytogenetic abnormalities, the PFS difference was more pronounced: 21.4 months with ixazomib versus 9.7 months with placebo (P = 0.02).

Treatment was discontinued in 62% of patients in the ixazomib cohort and 63% in the placebo cohort; disease progression was the main reason for discontinuation (in 34% and 40% of patients, respectively), followed by adverse events (in 17% and 14%, respectively). The rates of adverse events were similar for both groups, but grade 3 or 4 thrombocytopenia was more frequent in the patients who received ixazomib (12% versus 7%).

Overall survival results from this study are awaited — the median survival had not been reached in either group at the time of reporting. The current results, however, have been sufficient for the FDA to approve the use of ixazomib in combination with lenalidomide and dexamethasone for patients with MM who have received at least one prior therapy.