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Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial

Title: Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial
Authors: Dimopoulos, MA; Gay, F; Schjesvold, F; Beksac, M; Hajek, R; Weisel, KC; Goldschmidt, H; Maisnar, V; Moreau, P; Min, CK; Pluta, A; Chng, W-J; Kaiser, M; Zweegman, S; Mateos, M-V; Spencer, A; Iida, S; Morgan, G; Suryanarayan, K; Teng, Z; Skacel, T; Palumbo, A; Dash, AB; Gupta, N; Labotka, R; Rajkumar, SV; on behalf of the TOURMALINE-MM3 study group
Publisher Information: Elsevier
Publication Year: 2019
Collection: White Rose Research Online (Universities of Leeds, Sheffield & York)
Description: Background Maintenance therapy following autologous stem cell transplantation (ASCT) can delay disease progression and prolong survival in patients with multiple myeloma. Ixazomib is ideally suited for maintenance therapy given its convenient once-weekly oral dosing and low toxicity profile. In this study, we aimed to determine the safety and efficacy of ixazomib as maintenance therapy following ASCT. Methods The phase 3, double-blind, placebo-controlled TOURMALINE-MM3 study took place in 167 clinical or hospital sites in 30 countries in Europe, the Middle East, Africa, Asia, and North and South America. Eligible participants were adults with a confirmed diagnosis of symptomatic multiple myeloma according to International Myeloma Working Group criteria who had achieved at least a partial response after undergoing standard-of-care induction therapy followed by high-dose melphalan (200 mg/m2) conditioning and single ASCT within 12 months of diagnosis. Patients were randomly assigned in a 3:2 ratio to oral ixazomib or matching placebo on days 1, 8, and 15 in 28-day cycles for 2 years following induction, high-dose therapy, and transplantation. The initial 3 mg dose was increased to 4 mg from cycle 5 if tolerated during cycles 1–4. Randomisation was stratified by induction regimen, pre-induction disease stage, and response post-transplantation. The primary endpoint was progression-free survival (PFS) by intention-to-treat analysis. Safety was assessed in all patients who received at least one dose of ixazomib or placebo, according to treatment actually received. This trial is registered with ClinicalTrials.gov, number NCT02181413, and follow-up is ongoing. Findings Between July 31, 2014, and March 14, 2016, 656 patients were enrolled and randomly assigned to receive ixazomib maintenance therapy (n=395) or placebo (n=261). With a median follow-up of 31 months (IQR 27·3–35·7), we observed a 28% reduction in the risk of progression or death with ixazomib versus placebo (median PFS 26·5 months [95% CI 23·7–33·8] vs 21·3 ...
Document Type: article in journal/newspaper
Language: unknown
ISSN: 0140-6736
Relation: Dimopoulos, MA, Gay, F, Schjesvold, F et al. (24 more authors) (2019) Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial. The Lancet, 393 (10168). pp. 253-264. ISSN: 0140-6736
Availability: https://eprints.whiterose.ac.uk/id/eprint/170658/
Accession Number: edsbas.E1634E39
Database: BASE