Two phase 3 studies of the oral proteasome inhibitor (PI) ixazomib for multiple myeloma (MM) in the maintenance setting: TOURMALINE-MM3, and -MM4.

TPS8068 Background: Extended treatment for MM, including maintenance therapy, can improve long-term outcomes; however, the feasibility of long-term treatment with current regimens is limited due to toxicities or the need for regular clinic visits. In the phase 3 study TOURMALINE-MM1, the oral PI ixazomib, when added to lenalidomide and dexamethasone, significantly improved progression-free survival (PFS) in patients (pts) with relapsed/refractory MM, with limited toxicities (Moreau et al. ASH 2015). The phase 3 trials TOURMALINE-MM3 (NCT02181413) and -MM4 (NCT02312258) will investigate single-agent ixazomib maintenance therapy in pts who received autologous stem cell transplantation (ASCT), and those who have not undergone ASCT, respectively. Methods: Both trials are randomized, double-blind, placebo-controlled, single-agent, multicenter studies. To be eligible for inclusion in TOURMALINE-MM3, adult pts (N = 652 planned) with newly-diagnosed MM must have received standard-of-care induction therapy including a PI and/or immunomodulatory drug-based regimen, followed by a conditioning regimen containing high-dose melphalan (200 mg/m2) and a single ASCT, within 12 months of diagnosis. Pts must have achieved a partial response (PR) or better by IMWG criteria, and be randomized no later than 115 days after ASCT. For TOURMALINE-MM4, pts (N = 761 planned) who have not undergone ASCT (due to frailty, advanced age [ ≥ 65 yrs], comorbidity, or other reasons) must have completed 6–12 months of initial standard-of-care therapy with a response of PR or better, and be randomized no later than 60 days after the last dose of initial therapy. For both trials, eligible pts will be randomized 3:2 to ixazomib or placebo given on days 1, 8, and 15 of 28-day cycles; 3 mg for cycles 1–4 and 4 mg for cycles 5–26, or until disease progression or intolerable toxicities. The primary endpoint for both trials is PFS, with a key secondary endpoint of overall survival (OS). Other secondary endpoints include response rate, time to first progression, second PFS, assessment of minimal residual disease, safety, and PFS and OS in pts with high-risk cytogenetics. Recruitment is ongoing. Clinical trial information: NCT02181413, NCT02312258.