Ibrutinib Dose Adherence and Therapeutic Efficacy in Non-Hodgkin Lymphoma: A Single-Center Experience

Orally administered targeted therapies, including ibrutinib, are increasingly used to treat non-Hodgkin lymphoma (NHL); however, little is known about the clinical impact of suboptimal dosing. Data on reasons and time frames for ibrutinib discontinuation, dose reductions, and treatment interruptions were collected on 170 NHL and chronic lymphocytic leukemia patients treated with ibrutinib at a single institution. Discontinuation of ibrutinib therapy and suboptimal dose adherence were associated with poor outcome. Background: As oral targeted agents, such as ibrutinib, become more widely used, understanding the impact of suboptimal dosing on overall survival (OS) and progression-free survival (PFS) outside of clinical trials is imperative. Patients and Methods: Data on ibrutinib discontinuation, dose reductions, and treatment interruptions were collected on 170 non-Hodgkin lymphoma and chronic lymphocytic leukemia (CLL; n = 115, 64%) patients treated with ibrutinib 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. Kaplan-Meier curves and log-rank tests were used to compare conditional survival outcomes beyond 8 weeks in patients with >= 80% dose adherence and patients with < 80% dose adherence. Results: Median OS among those who discontinued therapy for progression was poor (n = 51, 1.7 months; 95% confidence interval, 0.3-3.7). Lower dose adherence (< 80%) was associated with significantly worse PFS (P = .002) and OS (P = .021). However, among CLL patients, lower dose adherence was only associated with worse PFS (P = .043). Patients with early dose reductions had significantly worse PFS (P = .004) and OS (P = .014). Patients with dose interruptions lasting > 1 week had worse PFS (P = .047) but not OS (P = .577). Conclusion: In this observational study, non-Hodgkin lymphoma and CLL patients experienced poor outcomes after discontinuing ibrutinib for disease progression. The inferior survival related to suboptimal dose adherence of ibrutinib was predominantly due to 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. (C) 2018 Elsevier Inc. All rights reserved.