2025 - Real-world dosing patterns and outcomes in patients with chronic lymphocytic leukemia patients with or without dose adjustment of first-line ibrutinib

Introduction: Patients treated for chronic lymphocytic leukemia (CLL) with ibrutinib, a once-daily Bruton’s tyrosine kinase inhibitor with dosing flexibility options, may adjust their daily dose to help prevent recurrence or worsening of adverse events, while preserving efficacy. This real-world study describes outcomes for patients with CLL treated with first-line (1L) ibrutinib who did or did not have a dose adjustment.

Methods: Electronic medical records from the Acentrus database (1/1/2016-4/30/2022) were used to identify patients with CLL initiated on 1L ibrutinib (index date). The first 6 months post-index were used to identify patients who remained on a starting dose of 420 mg/day or with dose adjustment (reducing to a dose lower than 420 mg/day; reasons for adjustment not available). Treatment adherence (measured using proportion of days covered [PDC] and medication possession ratio [MPR]) and time to next treatment (TTNT) were described for patients with and without dose adjustment. Descriptive analyses are reported for all patients and for the subgroup with high cardiovascular (CV) risk, defined as having a pre-existing CV comorbidity or a high CV risk score (CV subgroup).

Results: In total, 1,171 patients with CLL were initiated on 1L ibrutinib at the recommended dose of 420 mg/day (Table). Of those, 1,038 (88.6%) remained on 420 mg for ≥6 months (mean age=70.2 years, 33.6% female, median follow-up: 30.5 months); 229 (19.6%) had a dose adjustment at any time post-index (median time to adjustment: 5.5 months) and 126 had an adjustment during the first 6 months (mean age=72.2 years, 42.9% female, median follow-up: 35.1 months). Mean PDC and MPR were descriptively higher in patients with dose adjustment (overall: PDC=0.81, MPR=0.84; CV subgroup: PDC=0.78, MPR=0.81) relative to patients with no adjustment (overall: PDC=0.70, MPR=0.73; CV subgroup: PDC=0.69, MPR=0.72). Median TTNT was not reached, regardless of the dose adjustment status; 12-month Kaplan-Meier rates were similar for patients with (overall: 89.1%; CV subgroup: 92.7%) and without adjustment (overall: 92.5%; CV subgroup: 92.0%).

Conclusions: Among patients with CLL initiating with standard-of-care 1L ibrutinib, 19.6% had a dose adjustment. Those with adjustment had descriptively higher treatment adherence with no detriment to TTNT, relative to those who maintained 420 mg/day starting dose, regardless of baseline CV risk. These findings are consistent with other real-world studies and suggest that ibrutinib dose adjustment can be an effective treatment strategy that does not negatively affect efficacy while being well-tolerated outside of clinical trials.