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Blood. 2018 Feb 22;131(8):855-863. doi: 10.1182/blood-2017-08-797886. Epub 2017 Dec 4.

Safety and efficacy of selinexor in relapsed or refractory multiple myeloma and Waldenstrom macroglobulinemia.

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Division of Medical Oncology & Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada.
The University of Toronto, Toronto, ON, Canada.
Department of Hematology, John Theurer Cancer Center, Hackensack, NJ.
Siteman Cancer Center, Washington University in Saint Louis, Saint Louis, MO.
Department of Internal Medicine, Division of Hematology, The Ohio State University, Columbus, OH.
Gabrail Cancer Institute, Canton, OH.
Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
Department of Oncology, Rigshospitalet, Copenhagen, Denmark.
Blood Cancer Research Program, Sarah Cannon Research Institute, Nashville, TN.
Division of Hematology & Oncology, Vanderbilt-Ingram Cancer Center/Vanderbilt University Medical Center, Nashville, TN.
Tom Baker Cancer Centre Division of Hematology, University of Calgary, Calgary, AB, Canada; and.
Karyopharm Therapeutics Inc, Newton, MA.


Novel therapies are needed for patients with relapsed or refractory multiple myeloma (MM). We conducted a multicenter, phase 1 study in advanced hematological malignancies to assess the safety, efficacy, and recommended phase 2 dose (RP2D) of oral selinexor, a selective inhibitor of the nuclear export protein XPO1. In the dose-escalation phase, 25 patients with heavily pretreated MM (22) or Waldenstrom macroglobulinemia (3) were administered selinexor (3-60 mg/m2) in 8 or 10 doses per 28-day cycle. In the dose-expansion phase, 59 patients with MM received selinexor at 45 or 60 mg/m2 with 20 mg dexamethasone, twice weekly in 28-day cycles, or selinexor (40 or 60 mg flat dose) without corticosteroids in 21-day cycles. The most common nonhematologic adverse events (AEs) were nausea (75%), fatigue (70%), anorexia (64%), vomiting (43%), weight loss (32%), and diarrhea (32%), which were primarily grade 1 or 2. The most common grade 3 or 4 AEs were hematologic, particularly thrombocytopenia (45%). Single-agent selinexor showed modest efficacy with an objective response rate (ORR) of 4% and clinical benefit rate of 21%. In contrast, the addition of dexamethasone increased the ORR with all responses of ‚Č•partial response occurring in the 45 mg/m2 selinexor plus 20 mg dexamethasone twice weekly cohort (ORR = 50%). Furthermore, 46% of all patients showed a reduction in MM markers from baseline. Based on these findings, we conclude that selinexor in combination with dexamethasone is active in heavily pretreated MM and propose a RP2D of 45 mg/m2 (80 mg) plus 20 mg dexamethasone given twice weekly. This trial was registered at as #NCT01607892.

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