@article{3105737,
    title = "Oral selinexor-dexamethasone for triple-class refractory multiple myeloma",
    author = "Chari, A. and Vogl, D.T. and Gavriatopoulou, M. and Nooka, A.K. and Yee, A.J. and Huff, C.A. and Moreau, P. and Dingli, D. and Cole, C. and Lonial, S. and Dimopoulos, M. and Stewart, A.K. and Richter, J. and Vij, R. and Tuchman, S. and Raab, M.S. and Weisel, K.C. and Delforge, M. and Cornell, R.F. and Kaminetzky, D. and Hoffman, J.E. and Costa, L.J. and Parker, T.L. and Levy, M. and Schreder, M. and Meuleman, N. and Frenzel, L. and Mohty, M. and Choquet, S. and Schiller, G. and Comenzo, R.L. and Engelhardt, M. and Illmer, T. and Vlummens, P. and Doyen, C. and Facon, T. and Karlin, L. and Perrot, A. and Podar, K. and Kauffman, M.G. and Shacham, S. and Li, L. and Tang, S. and Picklesimer, C. and Saint-Martin, J.-R. and Crochiere, M. and Chang, H. and Parekh, S. and Landesman, Y. and Shah, J. and Richardson, P.G. and Jagannath, S.",
    journal = "The New England journal of medicine",
    year = "2019",
    volume = "381",
    number = "8",
    pages = "727-738",
    publisher = "Massachussetts Medical Society",
    doi = "10.1056/NEJMoa1903455",
    keywords = "alkylating agent;  bortezomib;  carfilzomib;  daratumumab;  dexamethasone;  immunomodulating agent;  lenalidomide;  pomalidomide;  proteasome inhibitor;  selinexor;  antineoplastic agent;  cell receptor;  dexamethasone;  exportin 1 protein;  hydrazine derivative;  karyopherin;  KPT-330;  triazole derivative;  tumor marker, adult;  aged;  anemia;  Article;  bleeding;  blurred vision;  body weight loss;  cancer combination chemotherapy;  cancer patient;  cancer survival;  chromosome aberration;  confidence interval;  constipation;  controlled study;  coughing;  decreased appetite;  diarrhea;  dizziness;  drug dose reduction;  drug efficacy;  drug fever;  drug safety;  drug withdrawal;  dyspnea;  epistaxis;  Europe;  falling;  fatigue;  female;  hematologic disease;  high risk patient;  human;  hyperglycemia;  hypokalemia;  hyponatremia;  insomnia;  intention to treat analysis;  leukopenia;  low drug dose;  lymphocytopenia;  major clinical study;  male;  mental disease;  multicenter study;  multiple cycle treatment;  multiple myeloma;  nausea;  neutropenia;  overall survival;  peripheral edema;  phase 2 clinical trial;  pneumonia;  population research;  priority journal;  progression free survival;  sepsis;  side effect;  thrombocytopenia;  treatment duration;  treatment response;  United States;  upper respiratory tract infection;  very elderly;  vomiting;  antagonists and inhibitors;  blood;  chemically induced;  clinical trial;  drug administration;  drug resistance;  middle aged;  multiple myeloma;  oral drug administration;  survival analysis;  thrombocytopenia;  young adult, Administration, Oral;  Adult;  Aged;  Antineoplastic Combined Chemotherapy Protocols;  Biomarkers, Tumor;  Dexamethasone;  Drug Administration Schedule;  Drug Resistance, Neoplasm;  Female;  Humans;  Hydrazines;  Intention to Treat Analysis;  Karyopherins;  Male;  Middle Aged;  Multiple Myeloma;  Receptors, Cytoplasmic and Nuclear;  Survival Analysis;  Thrombocytopenia;  Triazoles;  Young Adult",
    abstract = "BACKGROUND Selinexor, a selective inhibitor of nuclear export compound that blocks exportin 1 (XPO1) and forces nuclear accumulation and activation of tumor suppressor proteins, inhibits nuclear factor κB, and reduces oncoprotein messenger RNA translation, is a potential novel treatment for myeloma that is refractory to current therapeutic options. METHODS We administered oral selinexor (80 mg) plus dexamethasone (20 mg) twice weekly to patients with myeloma who had previous exposure to bortezomib, carfilzomib, lenalidomide, pomalidomide, daratumumab, and an alkylating agent and had disease refractory to at least one proteasome inhibitor, one immunomodulatory agent, and daratumumab (triple-class refractory). The primary end point was overall response, defined as a partial response or better, with response assessed by an independent review committee. Clinical benefit, defined as a minimal response or better, was a secondary end point. RESULTS A total of 122 patients in the United States and Europe were included in the modified intention-to-treat population (primary analysis), and 123 were included in the safety population. The median age was 65 years, and the median number of previous regimens was 7; a total of 53% of the patients had high-risk cytogenetic abnormalities. A partial response or better was observed in 26% of patients (95% confidence interval, 19 to 35), including two stringent complete responses; 39% of patients had a minimal response or better. The median duration of response was 4.4 months, median progression-free survival was 3.7 months, and median overall survival was 8.6 months. Fatigue, nausea, and decreased appetite were common and were typically grade 1 or 2 (grade 3 events were noted in up to 25% of patients, and no grade 4 events were reported). Thrombocytopenia occurred in 73% of the patients (grade 3 in 25% and grade 4 in 33%). Thrombocytopenia led to bleeding events of grade 3 or higher in 6 patients. CONCLUSIONS Selinexor-dexamethasone resulted in objective treatment responses in patients with myeloma refractory to currently available therapies. (Funded by Karyopharm Therapeutics; STORM ClinicalTrials.gov number, NCT02336815. © 2019 Massachusetts Medical Society."
}