Selinexor plus low-dose bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma.

Journal Article (Journal Article;Multicenter Study)

Selinexor is an oral inhibitor of the nuclear export protein exportin 1. Preclinical studies demonstrated synergistic antimyeloma activity between selinexor and proteasome inhibitors (PI) through suppression of NF-κB signaling and nuclear retention of tumor suppressor proteins. We tested selinexor in combination with low-dose bortezomib and dexamethasone (SVd) for the treatment of relapsed or refractory multiple myeloma (MM). The primary objectives of this study were to determine the safety profile, overall response rate (ORR), and a recommended phase 2 dose (RP2D) of SVd. We enrolled 42 patients to receive selinexor (60, 80, or 100 mg orally) plus bortezomib (1.3 mg/m2 subcutaneously) and dexamethasone (20 mg orally) once or twice weekly in 21- or 35-day cycles. Patients had a median of 3 (range 1-11) prior lines of therapy, and 50% were refractory to a PI. Treatment-related grade 3 or 4 adverse events reported in ≥10% of patients were thrombocytopenia (45%), neutropenia (24%), fatigue (14%), and anemia (12%). Incidence (4 patients, 10%) and grade (≤2) of peripheral neuropathy were low. The ORR for the entire population was 63%: 84% ORR for PI nonrefractory and 43% for PI-refractory patients. The median progression-free survival for all patients was 9.0 months; 17.8 months for PI nonrefractory, and 6.1 months for PI refractory. SVd treatment produced high response rates in patients with relapsed or refractory MM, including borezomib-refractory MM, with no unexpected side effects. The RP2D is selinexor (100 mg once weekly), bortezomib (1.3 mg/m2 once weekly for 4 weeks), and dexamethasone (40 mg once weekly) per 35-day cycle. This trial was registered at as #NCT02343042.

Full Text

Duke Authors

Cited Authors

  • Bahlis, NJ; Sutherland, H; White, D; Sebag, M; Lentzsch, S; Kotb, R; Venner, CP; Gasparetto, C; Del Col, A; Neri, P; Reece, D; Kauffman, M; Shacham, S; Unger, TJ; Jeha, J; Saint-Martin, J-R; Shah, J; Chen, C

Published Date

  • December 13, 2018

Published In

Volume / Issue

  • 132 / 24

Start / End Page

  • 2546 - 2554

PubMed ID

  • 30352784

Pubmed Central ID

  • PMC6302280

Electronic International Standard Serial Number (EISSN)

  • 1528-0020

Digital Object Identifier (DOI)

  • 10.1182/blood-2018-06-858852


  • eng

Conference Location

  • United States