@article{3085534,
    title = "Improvement in overall survival with carfilzomib, lenalidomide, and dexamethasone in patients with relapsed or refractory multiple myeloma",
    author = "Siegel, D.S. and Dimopoulos, M.A. and Ludwig, H. and Facon, T. and Goldschmidt, H. and Jakubowiak, A. and San-Miguel, J. and Obreja, M. and Blaedel, J. and Stewart, A.K.",
    journal = "Journal of Clinical Oncology",
    year = "2018",
    volume = "36",
    number = "8",
    pages = "728-734",
    publisher = "American Society of Clinical Oncology",
    issn = "0732-183X, 1527-7755",
    doi = "10.1200/JCO.2017.76.5032",
    keywords = "bendamustine;  bortezomib;  carfilzomib;  cisplatin;  cyclophosphamide;  dexamethasone;  doxorubicin;  lenalidomide;  melphalan;  pomalidomide;  prednisone;  thalidomide;  antineoplastic agent;  carfilzomib;  dexamethasone;  lenalidomide;  oligopeptide, acute kidney failure;  adult;  anemia;  Article;  backache;  bronchitis;  cancer growth;  cancer mortality;  cancer recurrence;  comparative study;  constipation;  controlled study;  coughing;  diarrhea;  drug dose regimen;  drug efficacy;  drug withdrawal;  fatigue;  female;  fever;  heart failure;  human;  hypertension;  hypokalemia;  insomnia;  ischemic heart disease;  major clinical study;  male;  multicenter study;  multiple cycle treatment;  multiple myeloma;  muscle spasm;  nausea;  neutropenia;  outcome assessment;  overall survival;  peripheral neuropathy;  phase 3 clinical trial;  pneumonia;  priority journal;  progression free survival;  randomized controlled trial;  survival time;  thrombocytopenia;  treatment outcome;  upper respiratory tract infection;  viral upper respiratory tract infection;  mortality;  multiple myeloma;  pathology;  survival analysis;  tumor recurrence, Antineoplastic Combined Chemotherapy Protocols;  Dexamethasone;  Female;  Humans;  Lenalidomide;  Male;  Multiple Myeloma;  Neoplasm Recurrence, Local;  Oligopeptides;  Survival Analysis",
    abstract = "Purpose: In the ASPIRE study of carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide plus dexamethasone (Rd) in patients with relapsed or refractory multiple myeloma, progression-free survival was significantly improved in the carfilzomib group (hazard ratio, 0.69; two-sided P < .001). This prespecified analysis reports final overall survival (OS) data and updated safety results. Patients and Methods: Adults with relapsed multiple myeloma (one to three prior lines of therapy) were eligible and randomly assigned at a one-to-one ratio to receive KRd or Rd in 28-day cycles until withdrawal of consent, disease progression, or occurrence of unacceptable toxicity. After 18 cycles, all patients received Rd only. Progression-free survival was the primary end point; OS was a key secondary end point. OS was compared between treatment arms using a stratified log-rank test. Results: Median OS was 48.3 months (95% CI, 42.4 to 52.8 months) for KRd versus 40.4 months (95% CI, 33.6 to 44.4 months) for Rd (hazard ratio, 0.79; 95% CI, 0.67 to 0.95; one-sided P = .0045). In patients receiving one prior line of therapy, median OS was 11.4 months longer for KRd versus Rd; it was 6.5 months longer for KRd versus Rd among patients receiving ≥ two prior lines of therapy. Rates of treatment discontinuation because of adverse events (AEs) were 19.9% (KRd) and 21.5% (Rd). Grade ≥3 AE rates were 87.0% (KRd) and 83.3% (Rd). Selected grade ≥ 3 AEs of interest (grouped terms; KRd v Rd) included acute renal failure (3.8% v 3.3%), cardiac failure (4.3% v 2.1%), ischemic heart disease (3.8% v 2.3%), hypertension (6.4% v 2.3%), hematopoietic thrombocytopenia (20.2% v 14.9%), and peripheral neuropathy (2.8% v 3.1%). Conclusion: KRd demonstrated a statistically significant and clinically meaningful reduction in the risk of death versus Rd, improving survival by 7.9 months. The KRd efficacy advantage is most pronounced at first relapse. © 2018 by American Society of Clinical Oncology."
}