Phase 1 study of ixazomib alone or combined with lenalidomide-dexamethasone in Japanese patients with relapsed/refractory multiple myeloma.

We report the first clinical investigation conducted in Japan to confirm the safety, tolerability, and pharmacokinetics of ixazomib alone and combined with lenalidomide-dexamethasone (Rd) in Japanese patients with relapsed/refractory multiple myeloma. Adult patients with measurable disease and ≥2 prior lines of therapy received oral ixazomib 4.0 mg on days 1, 8, 15 alone or combined with lenalidomide 25 mg on days 1-21 and dexamethasone 40 mg on days 1, 8, 15, 22 in 28-day cycles. Fourteen patients who had received a median of seven prior therapies were enrolled (seven per cohort). One of six evaluable patients in each cohort experienced dose-limiting toxicities [diarrhea, nausea, hypokalemia, hypertension, thrombocytopenia, hyponatremia (ixazomib cohort); thrombocytopenia, and neutropenia (ixazomib + Rd cohort)]. The most common drug-related adverse events were neutropenia, thrombocytopenia, leukopenia, and lymphopenia. Drug-related grade ≥3 adverse events occurring in ≥3 patients per cohort were (ixazomib/ixazomib + Rd cohort, n): neutropenia (4/2), thrombocytopenia (3/2), and lymphopenia (5/2). Ixazomib was rapidly absorbed with a median T max of approximately 1-2-h post-dose, and had a geometric mean terminal half-life of 5-6 days. Of 13 response-evaluable patients, one achieved a partial response (duration ∼38 weeks; ixazomib cohort) and seven had stable disease.