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

Autor: Gasparetto C; Duke University Medical Center, Durham, NC, USA. cristina.gasparetto@duke.edu., Schiller GJ; David Geffen School of Medicine at UCLA, Los Angeles, CA, USA., Tuchman SA; University of North Carolina, Chapel Hill, NC, USA., Callander NS; Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA., Baljevic M; University of Nebraska Medical Center, Omaha, NE, USA., Lentzsch S; Colombia University, New York, NY, USA., Rossi AC; NYPH Weill Cornell, New York, NY, USA., Kotb R; Cancer Care Manitoba, Winnipeg, MB, Canada., White D; Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada., Bahlis NJ; Charbonneau Cancer Research Institute, Calgary, AB, Canada., Chen CI; Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada., Sutherland HJ; Vancouver General Hospital, Vancouver, BC, Canada., Madan S; Banner MD Anderson Cancer Center, Gilbert, AZ, USA., LeBlanc R; Maisonneuve-Rosemont Hospital, University of Montreal, Montreal, QC, Canada., Sebag M; Royal Victoria Hospital, Montreal, QC, Canada., Venner CP; Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada., Bensinger WI; Myeloma and Transplant Program, Swedish Cancer Institute, Seattle, WA, USA., Biran N; Hackensack Meridian Health, Hackensack University Medical Center, Teaneck, USA., Ammu S; Karyopharm Therapeutics Inc., Newton, MA, USA., Ben-Shahar O; Karyopharm Therapeutics Inc., Newton, MA, USA., DeCastro A; Karyopharm Therapeutics Inc., Newton, MA, USA., Van Domelen D; Karyopharm Therapeutics Inc., Newton, MA, USA., Zhou T; Karyopharm Therapeutics Inc., Newton, MA, USA., Zhang C; Karyopharm Therapeutics Inc., Newton, MA, USA., Bentur OS; Karyopharm Therapeutics Inc., Newton, MA, USA., Shah J; Karyopharm Therapeutics Inc., Newton, MA, USA., Shacham S; Karyopharm Therapeutics Inc., Newton, MA, USA., Kauffman M; Karyopharm Therapeutics Inc., Newton, MA, USA., Lipe B; University of Rochester Medical College, Rochester, NY, USA.
Jazyk: angličtina
Zdroj: British journal of cancer [Br J Cancer] 2022 Mar; Vol. 126 (5), pp. 718-725. Date of Electronic Publication: 2021 Nov 20.
DOI: 10.1038/s41416-021-01608-2
Abstrakt: 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/m 2 ) + 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/m 2 , 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
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