Biomaterial Database

Randomized, placebo-controlled, phase 3 study of perifosine combined with bortezomib and dexamethasone in patients with relapsed, refractory multiple myeloma previously treated with bortezomib. 2020

Paul G Richardson, and Arnon Nagler, and Dina Ben-Yehuda, and Ashraf Badros, and Parameswaran N Hari, and Roman Hajek, and Ivan Spicka, and Hakan Kaya, and Richard LeBlanc, and Sung-Soo Yoon, and Kihyun Kim, and Joaquin Martinez-Lopez, and Moshe Mittelman, and Ofer Shpilberg, and Paul Blake, and Teru Hideshima, and Kathleen Colson, and Jacob P Laubach, and Irene M Ghobrial, and Merav Leiba, and Moshe E Gatt, and Peter Sportelli, and Michael Chen, and Kenneth C Anderson

Jerome Lipper Center for Multiple Myeloma Research Dana-Farber Cancer Institute Boston Massachusetts USA.

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]; P = .287); overall response rates were 20% and 27%, respectively. Conversely, median overall survival (OS) was 141.9 weeks and 83.3 weeks (hazard ratio 0.734 [0.380-1.419]; P = .356). Overall, 61% and 55% of patients in the perifosine and placebo arms reported grade 3/4 adverse events, including thrombocytopenia (26% vs 14%), anemia (7% vs 8%), hyponatremia (6% vs 8%), and pneumonia (9% vs 3%). These findings demonstrate no PFS benefit from the addition of perifosine to bortezomib-dexamethasone in this study of relapsed/refractory MM, but comparable safety and OS.