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 (University of California)
Hillmen, Peter (St. James University Hospital)
Coutre, Steven E (Stanford University School of Medicine)
Barr, Paul M (University of Rochester Cancer Center)
Fraser, Graeme (McMaster University (Canadà))
Tedeschi, Alessandra (ASST Grande Ospedale Metropolitano Niguarda)
Burger, Jan A. (University of Texas MD Anderson Cancer Center)
Dilhuydy, Marie-Sarah (Centre Hospitalier Universitaire Hopitaux de Bordeaux)
Hess, Georg (Universitats Medizin Mainz)
Moreno Atanasio, Carol (Institut d'Investigació Biomèdica Sant Pau)
Cramer, Paula (University of Cologne)
Liu, Emily (Pharmacyclics LLC. an AbbVie Company)
Chang, Stephen (Pharmacyclics LLC. an AbbVie Company)
Vermeulen, Jessica (Janssen Research & Development)
Styles, Lori (Pharmacyclics LLC. an AbbVie Company)
Howes, Angela (Janssen Research & Development)
James, Danelle F. (Pharmacyclics LLC. an AbbVie Company)
Patel, Kalpesh (Janssen Pharmaceuticals. Inc)
Graef, Thorsten (Pharmacyclics LLC. an AbbVie Company)
Valentino, Rudolph (Pharmacyclics LLC. an AbbVie Company)
Universitat Autònoma de Barcelona

Date:	2018
Abstract:	Ibrutinib, a Bruton's tyrosine kinase inhibitor, has become a standard treatment for patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The present pooled safety analysis of 4 randomized controlled studies demonstrated a favorable benefit/risk profile for ibrutinib in patients with CLL/SLL and mantle cell lymphoma. 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. 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. 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. These results from an integrated analysis support a favorable benefit/risk profile of ibrutinib in patients with CLL/SLL and MCL.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Adverse events ; Benefit/risk profile ; Bruton's tyrosine kinase inhibitor ; Exposure-adjusted incidence rate ; Pooled analysis
Published in:	Clinical Lymphoma, Myeloma & Leukemia, Vol. 18 Núm. 10 (october 2018) , p. 648-657.e15, ISSN 2152-2669

DOI: 10.1016/j.clml.2018.06.016
PMID: 30061088

25 p, 1.7 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles