Suboptimal Dosing of Ibrutinib in Patients With CLL
Posted: Thursday, August 1, 2019
Patients with non-Hodgkin lymphoma and chronic lymphocytic leukemia (CLL) experienced poor outcomes after discontinuing treatment with ibrutinib for disease progression, according to single-center findings published in Clinical Lymphoma, Myeloma, & Leukemia. Paul M. Barr, MD, of the University of Rochester Medical Center, Rochester, New York, and colleagues found that the inferior survival related to suboptimal dose adherence of ibrutinib was predominantly because of early dose reduction.
“These data confirm poor survival in CLL and lymphoma patients alike after ibrutinib discontinuation and support recommendations for full dose at treatment initiation,” the authors concluded.
Researchers collected data on ibrutinib discontinuation, dose reductions, and treatment interruptions from 170 patients with non-Hodgkin lymphoma and CLL who were treated at a single institution. Ibrutinib dose adherence was calculated as the proportion of days in which ibrutinib was administered out of the total number of days ibrutinib was prescribed in the first 8 weeks.
Among the 51 patients who discontinued therapy for disease progression, the median overall survival was poor (1.7 months). Lower dose adherence (< 80%) was associated with significantly worse progression-free survival (P = .002) and overall survival (P = .021). However, among those with CLL, lower dose adherence was associated only with worse progression-free survival (P = .043). Patients with early dose reductions had significantly worse progression-free survival (P = .004) and overall survival (P = .14). In addition, patients who had dose interruptions lasting more than 1 week had worse progression-free survival (P = .047) but not overall survival (P = .577) rates.
“Together, these analyses raise concerns for the development of therapeutic resistance for patients receiving suboptimal ibrutinib dosing,” the authors added. “However, bias may arise because reduced adherence early in the treatment course may also be related to underlying illness limiting adherence or influencing physician prescribing.”
Disclosure: The study authors reported no conflicts of interest.