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Safety Analysis of Four Randomized Controlled Studies of Ibrutinib in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma or Mantle Cell Lymphoma.
O'Brien, Susan; Hillmen, Peter; Coutre, Steven; Barr, Paul M; Fraser, Graeme; Tedeschi, Alessandra; Burger, Jan A; Dilhuydy, Marie-Sarah; Hess, Georg; Moreno, Carol; Cramer, Paula; Liu, Emily; Chang, Stephen; Vermeulen, Jessica; Styles, Lori; Howes, Angela; James, Danelle F; Patel, Kalpesh; Graef, Thorsten; Valentino, Rudolph.
Afiliación
  • O'Brien S; Chao Family Comprehensive Cancer Center, University of California, Irvine, Orange, CA. Electronic address: obrien@uci.edu.
  • Hillmen P; The Leeds Teaching Hospitals, St. James University Hospital, Leeds, United Kingdom.
  • Coutre S; Stanford University School of Medicine, Stanford, CA.
  • Barr PM; Wilmot Cancer Institute, University of Rochester Cancer Center, Rochester, NY.
  • Fraser G; Juravinski Cancer Centre, McMaster University, Hamilton, ON, Canada.
  • Tedeschi A; ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.
  • Burger JA; University of Texas MD Anderson Cancer Center, Houston, TX.
  • Dilhuydy MS; Centre Hospitalier Universitaire Hopitaux de Bordeaux, Pessac, France.
  • Hess G; Universitats Medizin Mainz, Mainz, Germany.
  • Moreno C; Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
  • Cramer P; University of Cologne, German CLL Study Group, Cologne, Germany.
  • Liu E; Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA.
  • Chang S; Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA.
  • Vermeulen J; Janssen Research & Development, Leiden, The Netherlands.
  • Styles L; Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA.
  • Howes A; Janssen Research & Development, Raritan, NJ.
  • James DF; Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA.
  • Patel K; Janssen Pharmaceuticals, Inc, Titusville, NJ.
  • Graef T; Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA.
  • Valentino R; Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA.
Clin Lymphoma Myeloma Leuk ; 18(10): 648-657.e15, 2018 10.
Article en En | MEDLINE | ID: mdl-30061088
BACKGROUND: Multiple studies have demonstrated the efficacy and safety of ibrutinib for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma (MCL). This first-in-class inhibitor of Bruton's tyrosine kinase has become a standard treatment for patients with CLL and MCL. PATIENTS AND METHODS: We conducted an integrated safety analysis to characterize the frequency, severity, natural history, and outcomes of adverse events (AEs) with ibrutinib versus comparators. Data were pooled from 4 completed randomized controlled studies that had included 756 ibrutinib-treated and 749 comparator-treated patients with CLL/SLL or relapsed/refractory MCL. Safety analyses included reporting of AEs using crude and exposure-adjusted incidence rates. RESULTS: The median treatment duration was 13.3 months (maximum, 28.2 months) for ibrutinib and 5.8 months (maximum, 27.3 months) for comparators. When adjusted for exposure, diarrhea, atrial fibrillation, and hypertension were the only common grade ≥ 3 AEs more often reported with ibrutinib than with the comparators. Dose reductions (7% vs. 14%) and discontinuation (12% vs. 16%) because of AEs occurred less often with ibrutinib, and deaths due to AEs occurred at similar rates (6% vs. 7%). When adjusted for exposure, the corresponding data were all lower with ibrutinib than with the comparators (0.06 vs. 0.22, 0.11 vs. 0.22, and 0.06 vs. 0.09 patient-exposure-years, respectively). The prevalence of common grade 3/4 AEs with ibrutinib generally decreased over time, with the exception of hypertension. CONCLUSION: These results from an integrated analysis support a favorable benefit/risk profile of ibrutinib in patients with CLL/SLL and MCL.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Linfocítica Crónica de Células B / Protocolos de Quimioterapia Combinada Antineoplásica / Linfoma de Células del Manto / Seguridad del Paciente Tipo de estudio: Clinical_trials / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Clin Lymphoma Myeloma Leuk Asunto de la revista: NEOPLASIAS Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Linfocítica Crónica de Células B / Protocolos de Quimioterapia Combinada Antineoplásica / Linfoma de Células del Manto / Seguridad del Paciente Tipo de estudio: Clinical_trials / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Clin Lymphoma Myeloma Leuk Asunto de la revista: NEOPLASIAS Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos