Abstract
The objective in this study was to characterize the pattern of the treatment-related lymphocytosis curve in chronic lymphocytic leukemia (CLL) patients treated with ibrutinib, and assess the relationship between the baseline factors and absolute lymphocyte counts (ALC). The PCYC-1102-CA study was a five-arm phase Ib/II open-label, nonrandomized, multicenter study in CLL/SLL. The arms and accruals were 420 and 840 mg/day treatment-naive elderly CLL/SLL (N = 27 and N = 4, respectively), 420 and 840 mg/day relapsed/refractory CLL/SLL (N = 27 and N = 34, respectively), and 420 mg/day high-risk CLL/SLL (N = 24). The results were generated through statistical modeling using data from a clinical trial (PCYC-1102) in five cohorts of treatment-naïve or relapsed/refractory CLL patients treated at 420 and 840 mg daily of ibrutinib. In cases in which the initial increase in ALC doubles by day 28, it takes patients longer to reach their maximum ALC when compared with those with a lower rate of increase. Our models show that all of the cohorts exhibited the same pattern of treatment-related lymphocytosis from ibrutinib, and there are no significant differences between cohorts, including no detectable dose effect. The ALC of the majority of patients return to baseline ALC values by the end of cycle 5.
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Acknowledgments
The authors would like to thank the PCYC-1102 study team, especially Eric Hedrick, Tasheda Navarro, and Clara Plascencia. The authors also thank Raymond Lee and his programming team for their support in data extraction and cleaning. Finally, the authors are grateful for the constructive comments from our anonymous reviewers who made excellent suggestions and enhanced our analyses of the data.
Contributions
A.H., R.I., D. F.J., and L.A.K. designed and managed the trial and the data collection; D.D.S. and L.G. performed the statistical modeling; D.D.S., L.G., M.C., and F.C. interpreted the data and wrote the manuscript; and M.F. and J.J.B. critically reviewed the manuscript and made substantive contributions to answer the research questions. All authors gave final approval for the manuscript.
Conflict of interest
D.D.S. serves on the Board of Directors and is a shareholder of Pharmacyclics, Inc. D.F.J., L.A.K., M.C., F.C., M.F., and J.B. are shareholders and employees of Pharmacyclics, Inc. A.H. and R.I. are shareholders of Pharmacyclics, Inc. L.G. The authors have no conflict of interest.
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Smith, D.D., Goldstein, L., Cheng, M. et al. Modeling absolute lymphocyte counts after treatment of chronic lymphocytic leukemia with ibrutinib. Ann Hematol 94, 249–256 (2015). https://doi.org/10.1007/s00277-014-2187-9
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DOI: https://doi.org/10.1007/s00277-014-2187-9