Once weekly selinexor, carfilzomib and dexamethasone in carfilzomib non-refractory multiple myeloma patients.

Journal Article (Journal Article)

BACKGROUND: Proteasome inhibitors (PIs), including carfilzomib, potentiate the activity of selinexor, a novel, first-in-class, oral selective inhibitor of nuclear export (SINE) compound, in preclinical models of multiple myeloma (MM). METHODS: The safety, efficacy, maximum-tolerated dose (MTD) and recommended phase 2 dose (RP2D) of selinexor (80 or 100 mg) + carfilzomib (56 or 70 mg/m2) + dexamethasone (40 mg) (XKd) once weekly (QW) was evaluated in patients with relapsed refractory MM (RRMM) not refractory to carfilzomib. RESULTS: Thirty-two patients, median prior therapies 4 (range, 1-8), were enrolled. MM was triple-class refractory in 38% of patients and 53% of patients had high-risk cytogenetics del(17p), t(4;14), t(14;16) and/or gain 1q. Common treatment-related adverse events (all/Grade 3) were thrombocytopenia 72%/47% (G3 and G4), nausea 72%/6%, anaemia 53%/19% and fatigue 53%/9%, all expected and manageable with supportive care and dose modifications. MTD and RP2D were identified as selinexor 80 mg, carfilzomib 56 mg/m2, and dexamethasone 40 mg, all QW. The overall response rate was 78% including 14 (44%) ≥ very good partial responses. Median progression-free survival was 15 months. CONCLUSIONS: Weekly XKd is highly effective and well-tolerated. These data support further investigation of XKd in patients with MM.

Full Text

Duke Authors

Cited Authors

  • Gasparetto, C; Schiller, GJ; Tuchman, SA; Callander, NS; Baljevic, M; Lentzsch, S; Rossi, AC; Kotb, R; White, D; Bahlis, NJ; Chen, CI; Sutherland, HJ; Madan, S; LeBlanc, R; Sebag, M; Venner, CP; Bensinger, WI; Biran, N; Ammu, S; Ben-Shahar, O; DeCastro, A; Van Domelen, D; Zhou, T; Zhang, C; Bentur, OS; Shah, J; Shacham, S; Kauffman, M; Lipe, B

Published Date

  • March 2022

Published In

Volume / Issue

  • 126 / 5

Start / End Page

  • 718 - 725

PubMed ID

  • 34802051

Pubmed Central ID

  • PMC8605887

Electronic International Standard Serial Number (EISSN)

  • 1532-1827

Digital Object Identifier (DOI)

  • 10.1038/s41416-021-01608-2

Language

  • eng

Conference Location

  • England