Safety Analysis of Four Randomized Controlled Studies of Ibrutinib in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma or Mantle Cell Lymphoma
Por:
O'Brien, S, Hillmen, P, Coutre, S, Barr, PM, Fraser, G, Tedeschi, A, Burger, JA, Dilhuydy, MS, Hess, G, Moreno, C, Cramer, P, Liu, E, Chang, S, Vermeulen, J, Styles, L, Howes, A, James, DF, Patel, K, Graef, T, Valentino, R
Publicada:
1 oct 2018
Resumen:
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.
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. (C) 2018 The Authors. Published by Elsevier Inc.
Filiaciones:
O'Brien, S:
Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Orange, CA 92668 USA
Hillmen, P:
St James Univ Hosp, Leeds Teaching Hosp, Leeds, W Yorkshire, England
Coutre, S:
Stanford Univ, Sch Med, Stanford, CA USA
Barr, PM:
Univ Rochester, Wilmot Canc Inst, Canc Ctr, Rochester, NY USA
Fraser, G:
McMaster Univ, Juravinski Canc Ctr, Hamilton, ON, Canada
Tedeschi, A:
ASST Grande Osped Metropolitano Niguarda, Milan, Italy
Burger, JA:
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA
Dilhuydy, MS:
CHU Hop Bordeaux, Pessac, France
Hess, G:
Univ Med Mainz, Mainz, Germany
Moreno, C:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Cramer, P:
Univ Cologne, German CLL Study Grp, Cologne, Germany
Liu, E:
Pharmacycl LLC, Sunnyvale, CA USA
Chang, S:
Pharmacycl LLC, Sunnyvale, CA USA
Vermeulen, J:
Janssen Res & Dev, Leiden, Netherlands
Styles, L:
Pharmacycl LLC, Sunnyvale, CA USA
Howes, A:
Janssen Res & Dev, Raritan, NJ USA
James, DF:
Pharmacycl LLC, Sunnyvale, CA USA
Patel, K:
Janssen Pharmaceut Inc, Titusville, NJ USA
Graef, T:
Pharmacycl LLC, Sunnyvale, CA USA
Valentino, R:
Pharmacycl LLC, Sunnyvale, CA USA
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