1. Once weekly selinexor, carfilzomib and dexamethasone in carfilzomib non-refractory multiple myeloma patients
- Author
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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 I, 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
- Subjects
Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Oncology and Carcinogenesis ,Rare Diseases ,Cancer ,Hematology ,Clinical Research ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Adult ,Aged ,Antineoplastic Combined Chemotherapy Protocols ,Dexamethasone ,Drug Administration Schedule ,Female ,Humans ,Hydrazines ,Male ,Maximum Tolerated Dose ,Middle Aged ,Multiple Myeloma ,Oligopeptides ,Survival Analysis ,Translocation ,Genetic ,Treatment Outcome ,Triazoles ,Public Health and Health Services ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
BackgroundProteasome 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).MethodsThe 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.ResultsThirty-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.ConclusionsWeekly XKd is highly effective and well-tolerated. These data support further investigation of XKd in patients with MM.
- Published
- 2022