Once weekly selinexor, carfilzomib and dexamethasone in carfilzomib non-refractory multiple myeloma patients.
British journal of cancer
washington; seattle; swedish cancer
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
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
CONCLUSIONS: Weekly XKd is highly effective and well-tolerated. These data support further investigation of XKd in patients with MM.
Gasparetto, Cristina; Schiller, Gary J; Tuchman, Sascha A; Callander, Natalie S; Baljevic, Muhamed; Lentzsch, Suzanne; Rossi, Adriana C; Kotb, Rami; White, Darrell; Bahlis, Nizar J; Chen, Christine I; Sutherland, Heather J; Madan, Sumit; LeBlanc, Richard; Sebag, Michael; Venner, Christopher P; Bensinger, William; Biran, Noa; Ammu, Sonia; Ben-Shahar, Osnat; DeCastro, Andrew; Van Domelen, Dane; Zhou, Tianjun; Zhang, Chris; Bentur, Ohad S; Shah, Jatin; Shacham, Sharon; Kauffman, Michael; and Lipe, Brea, "Once weekly selinexor, carfilzomib and dexamethasone in carfilzomib non-refractory multiple myeloma patients." (2021). Articles, Abstracts, and Reports. 5509.