Reducing ibrutinib dose shown not to adversely affect CLL patient outcome

In February 2017 in a correspondence in the British Journal of Haematology, Anthony R. Mato, Abramson Cancer Center, University of Pennsylvania, Philadelphia, and colleagues published results of a multicenter retrospective study into the efficacy of dose reduction in CLL patients. Retrospective chart review was conducted for ibrutinib treated CLL patients at three institutions between January 2010 and October 2015. Reduced dose was defined as being below the approved US FDA daily dose of 420 mg for longer than 2 months at treatment initiation or within 3 months of initiation.

Key highlights:

  • Identified 197 CLL pts treated with ibrutinib (R/R CLL = 81% pts, ND CLL = 19%)
    • Reduced ibrutinib dose = 37 pts (19%)
  • No reported difference in baseline patient characteristics
  • Median ibrutinib daily dosage:
    • Standard dose group = 5.1 mg/kg
    • Reduced dose group = 4.3 mg/kg
  • Results:
    • ORR: Standard dose = 85%, Reduced dose = 84%
    • Median OS: Standard dose = not reached, Reduced dose = not reached (P = 0.5)
    • Median PFS: Standard dose = 37.4 months, Reduced dose = not reached (P = 0.6)
  • Cox-regression univariate analysis:
    • PFS: standard reduced dose = 1.2 (95% CI, 0.5–2.6)
    • OS: standard reduced dose = 0.6 (95% CI, 0.14–2.7)
  • Reasons for ibrutinib dose reduction: G.I. toxicity 16%, bleeding (11%), pharmacokinetic considerations (11%)

In conclusion, the authors state that to their knowledge “this report describes the largest real-world experience of reduced dose ibrutinib in CLL patients” and that reducing ibrutinib dose has been shown for the first time to not result in poorer clinical outcome. The authors argue that future studies should consider weight-based dosing in light of this data, and that reduced dose may result in treatment cost-savings. The authors also acknowledge the small, retrospective nature of this study as being limitations, but they suggest that the data may provide reassurance in cases where reduction is required.

  1. Mato A.R. et al. Comparable outcomes in chronic lymphocytic leukaemia (CLL) patients treated with reduced-dose ibrutinib: results from a multi-centre study. British Journal of Haematology. 2017 Feb 21. DOI: 1111/bjh.14540. [Epub ahead of print: 2017 Feb 21].



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