Randomized, placebo-controlled, phase 3 study of perifosine combined with bortezomib and dexamethasone in patients with relapsed, refractory multiple myeloma previously treated with bortezomib.

Perifosine, an investigational, oral, synthetic alkylphospholipid, inhibits signal transduction pathways of relevance in multiple myeloma (MM) including PI3K/Akt. Perifosine demonstrated anti-MM activity in preclinical studies and encouraging early-phase clinical activity in combination with bortezomib. A randomized, double-blind, placebo-controlled phase 3 study was conducted to evaluate addition of perifosine to bortezomib-dexamethasone in MM patients with one to four prior therapies who had relapsed following previous bortezomib-based therapy. The primary endpoint was progression-free survival (PFS). The study was discontinued at planned interim analysis, with 135 patients enrolled. Median PFS was 22.7 weeks (95% confidence interval 16·0-45·4) in the perifosine arm and 39.0 weeks (18.3-50.1) in the placebo arm (hazard ratio 1.269 [0.817-1.969];

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© 2020 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.

Déclaration de conflit d'intérêts

P.G.R. received research support from Oncopeptides, Celgene, Takeda, and Bristol‐Myers Squibb and served as advisory committee member for Karyopharm, Oncopeptides, Celgene, Takeda, Amgen, Janssen, and Sanofi. P.N.H. received research funding from Takeda and Celgene, and served as a consultant for Takeda, Celgene, Bristol‐Myers Squibb, Janssen, Spectrum, Pharmacyclics, and Kite. R.H. received consulting fees, honoraria, and research funding from Amgen, Takeda, Celgene, Janssen, Abbvie, Novartis, PharmaMar, and BMS. H.K. served as a consultant and also served on a Speakers Bureau for Takeda. J.M.‐L. received research funding from BMS, Janssen, Novartis, and Celgene, and served as a consultant for Janssen, Novartis, Celgene, and Roche. P.B. was an employee of Aeterna Zentaris. K.C. served as a consultant for Celgene. I.M.G. served as a consultant for GSK, Sanofi, Janssen, Takeda, Celgene, Karyopharm, AbbVie, GNS, Cellectar, Medscape, Genentech, Adaptive, BMS, Aptitude, Curio Science, and Oncopeptides, and served as an advisor for GSK, AbbVie, and BMS. P.S. was an employee and had equity interest in Keryx Biopharmaceuticals. M.C. served as a consultant for Keryx Biopharmaceuticals. K.C.A. served as a consultant for Celgene, Millennium Pharmaceuticals, Bristol Myers Squibb, Janssen, Gilead, and Sanofi, and was a scientific founder of Oncopep and C4 Therapeutics.