2027 - Real-world assessment of dosing patterns and treatment outcomes in patients with chronic lymphocytic leukemia who initiated first-line single-agent ibrutinib in an integrated claims-based database

Introduction: In patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who are receiving ibrutinib (IBR), a once-daily Bruton’s tyrosine kinase inhibitor, dose modifications may be recommended for managing clinical events during treatment.

Methods: This retrospective cohort study aimed to describe real-world dosing patterns and treatment outcomes in CLL/SLL patients who did or did not have a dose adjustment (DA) after initiation of first-line (1L) single-agent IBR. The study was conducted using health insurance claims data from the Komodo Health payer complete dataset, derived from >150 private insurers in the U.S. and >140 million individuals from 2015 to 2022 with age and geographic representation of the insured U.S. population including patients from the community practice setting. Included CLL/SLL patients initiated on 1L single-agent IBR at the recommended dose of 420 mg/day on or after March 4, 2016. The IBR initiation date was defined as the index date and 1L single-agent IBR treatment was defined as having no other CLL/SLL treatment within 12 months before and 28 days after index. Dosing patterns between index and the end of patient follow-up (earliest of initiation of next line of therapy, end of enrollment, or end of data availability) were described. Further, patients with or without a DA to a dose lower than 420 mg/day during the first 6 months after index were classified into two separate cohorts. Adherence (measured by proportion of days covered [PDC] and medication possession ratio [MPR]) and time to next treatment (TTNT; a surrogate measure of treatment efficacy) after IBR initiation were assessed descriptively in these two cohorts. All analyses were repeated in the corresponding subgroups of patients with high cardiovascular (CV) risk (defined as pre-existing CV comorbidity or high-risk CHA2DS2-VASc score).

Results: 3174 patients initiated 1L IBR at 420 mg/day. Mean age at index was 67 years. Over a median follow-up period of 19.9 months, 18% (n=562) had a DA; of those, 50% (n=280) experienced DA within the first 6 months after IBR initiation, 85% (n=478) received 280 mg/day as the first reduced dose, 70% (n=396) stayed on the first reduced dose for the remainder of 1L therapy, 12% (n=68) returned to 420 mg/day, and 13% (n=74) further reduced the dose. Similar dosing patterns were observed in the subgroup of high CV risk patients (n=2334). In the cohort of patients with a DA within the first 6 months after IBR initiation (n=280) and the cohort of patients who remained on 420 mg/day for ≥6 months (n=2894), 55% and 65% of patients were male, the mean baseline Quan Charlson Comorbidity Index score was 2.87 and 2.83, and 77% (n=216) and 73% (n=2118) had high CV risk, respectively. Mean PDC was 0.67 and 0.68, and mean MPR was 0.68 and 0.70 in patients with and without a DA, respectively. In the analysis of TTNT, the Kaplan-Meier estimates were similar between the two cohorts (Figure); the probability of not initiating the next line of therapy within 12 months was 90% (95% confidence interval [CI]: 87%, 94%) and 92% (95% CI: 91%, 93%) for the cohort with a DA and the cohort without a DA, respectively. Findings of adherence and TTNT were similar for the high CV risk subgroups.

Conclusions: In CLL/SLL patients who initiated 1L single-agent IBR at a dose of 420 mg/day, only 18% had a DA during a median follow-up of 20 months, suggesting that the recommended starting dose was generally well-tolerated. Measures of adherence and probabilities of not initiating the next line of therapy were numerically comparable in patients with or without a DA. These findings highlight that IBR dose modification may be an effective treatment strategy when dose modifications are warranted in the real-world.