Safety and efficacy of selinexor in relapsed or refractory multiple myeloma and Waldenstrom macroglobulinemia - PubMed (original) (raw)

Clinical Trial

. 2018 Feb 22;131(8):855-863.

doi: 10.1182/blood-2017-08-797886. Epub 2017 Dec 4.

David Siegel 3, Martin Gutierrez 3, Meagan Jacoby 4, Craig C Hofmeister 5, Nashat Gabrail 6, Rachid Baz 7, Morten Mau-Sorensen 8, Jesus G Berdeja 9, Michael Savona 10, Lynn Savoie 11, Suzanne Trudel 1 2, Nuchanan Areethamsirikul 1 2, T J Unger 12, Tami Rashal 12, Tim Hanke 12, Michael Kauffman 12, Sharon Shacham 12, Donna Reece 1 2

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Free article

Clinical Trial

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

Christine Chen et al. Blood. 2018.

Free article

Abstract

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 ≥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 clinicaltrials.gov as #NCT01607892.

© 2018 by The American Society of Hematology.

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