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

Cristina Gasparetto, Gary J. Schiller, Sascha A. Tuchman, Natalie S. Callander, Muhamed Baljevic, Suzanne Lentzsch, Adriana C. Rossi, Rami Kotb, Darrell White, Nizar J. Bahlis, Christine I. Chen, Heather J. Sutherland, Sumit Madan, Richard LeBlanc, Michael Sebag, Christopher P. Venner, William I. Bensinger, Noa Biran, Sonia Ammu, Osnat Ben-ShaharAndrew DeCastro, Dane Van Domelen, Tianjun Zhou, Chris Zhang, Ohad S. Bentur, Jatin Shah, Sharon Shacham, Michael Kauffman, Brea Lipe

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)718-725
Number of pages8
JournalBritish journal of cancer
Volume126
Issue number5
DOIs
StatePublished - Mar 23 2022
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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