Impact of adherence to ibrutinib on clinical outcomes in real-world patients with chronic lymphocytic leukemia

Abstract

Background: Chronic lymphocytic leukemia (CLL) is a B-cell neoplasm with clonal expansion of small lymphocytes. Ibrutinib, an irreversible inhibitor of Bruton tyrosine kinase (BTK), is a first-line treatment option, and recent data suggest that strict adherence is directly related to clinical outcomes. Objectives: The primary objective of this study was to quantify ibrutinib adherence rates in real-world patients with CLL on ibrutinib; secondary outcomes included progression-free survival and overall survival. Methods: This retrospective study included subjects who were treated at a large academic medical center over approximately 5 years. Subjects were at least 18 years, diagnosed with CLL or small lymphocytic lymphoma, and treated with ibrutinib monotherapy for at least 6 months. Adherence was quantified using the medication possession ratio (MPR), which is the ratio of the sum of days' supply of medication in a period over the number of days in that period, and was based on fill history from the medical center's specialty pharmacy. Results: For the 32 subjects in this study, the mean ibrutinib adherence rate was 91.7% (range, 84.4%-100%). Only 3 subjects had disease progression, and 1 death was recorded while on therapy (all with MPR < 95%); therefore, analyses of clinical outcomes were unable to be assessed due to a low number of events. There were no statistically significant differences in rates of adherence based on baseline characteristics and adverse drug events. Conclusion: In patients with CLL treated with ibrutinib, mean adherence was 91.7%, which is lower than rates seen in clinical trials.

Real-World Comparison of First-Line Treatment Adherence Between Single-Agent Ibrutinib and Acalabrutinib in Patients with Chronic Lymphocytic Leukemia

“… 32 A second follow-up study reported a mean PDC of 95% (range: 65–100%) among patients treated with ibrutinib for at least 6 months. 33 The mean PDC and MPR reported in the current study for patients treated with ibrutinib with at least 6 months of LOT duration were similarly high at 85% and may be more generalizable, as the data came from a larger cohort of 1374 patients treated with ibrutinib in 15 academic and 12 non-teaching hospital systems across 15 US states (compared to only 32–149 patients from one or two centers).…”

Results from a Real-World Multicenter Analysis of 482 Patients with Chronic Lymphocytic Leukemia Treated with Ibrutinib: A Look at Racial Differences

“…For patients on a treat-to-progression regimen, treatment interruptions may have impacted overall disease outcomes. A recent study by Collins et al assessed impact of adherence to ibrutinib on clinical outcomes using proportion of days covered (PDC) as a measurement of adherence and found that patients with PDC > 95% during the first 6 months of treatment experienced fewer events of disease progression, but discontinued ibrutinib sooner and more often due to AEs compared with patients with PDC ≤ 95% [ 29 ]. The authors hypothesized that high PDC while the patient was on therapy led to more AEs, which could be indicative of tolerability issues with the dosage [ 29 ].…”

“…A recent study by Collins et al assessed impact of adherence to ibrutinib on clinical outcomes using proportion of days covered (PDC) as a measurement of adherence and found that patients with PDC > 95% during the first 6 months of treatment experienced fewer events of disease progression, but discontinued ibrutinib sooner and more often due to AEs compared with patients with PDC ≤ 95% [ 29 ]. The authors hypothesized that high PDC while the patient was on therapy led to more AEs, which could be indicative of tolerability issues with the dosage [ 29 ]. However, PDC only addresses adherence when a patient has an active prescription and does not account for any time after the patient discontinues therapy [ 29 ].…”

“…The authors hypothesized that high PDC while the patient was on therapy led to more AEs, which could be indicative of tolerability issues with the dosage [ 29 ]. However, PDC only addresses adherence when a patient has an active prescription and does not account for any time after the patient discontinues therapy [ 29 ].…”

Adherence to ibrutinib remains an unmet clinical need in chronic lymphocytic leukemia

“…In this issue of Leukemia & Lymphoma Collins et al (14) present the results of a retrospective, multicenter study wherein the authors assessed ibrutinib adherence and the impact of adherence on real-world clinical outcomes of CLL patients over the complete duration of ibrutinib treatment. .…”