Once weekly selinexor, carfilzomib and dexamethasone in carfilzomib non-refractory multiple myeloma patients.
Br J Cancer
; 126(5): 718-725, 2022 03.
Article
en En
| MEDLINE
| ID: mdl-34802051
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Oligopéptidos
/
Triazoles
/
Dexametasona
/
Hidrazinas
/
Mieloma Múltiple
Límite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Br J Cancer
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos