Impact of ibrutinib dose adjustment on TTNT in first-line CLL/SLL: a real-world analysis using target trial emulation

Ibrutinib, a once-daily Bruton's tyrosine kinase inhibitor (BTKi), is a standard-of-care first-line (1L) treatment for patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Dosing flexibility (adjustment to daily dose <420 mg/day) with ibrutinib can help prevent recurrence or worsening of adverse events, while maintaining long-term efficacy. This study compared time to next treatment (TTNT) among CLL/SLL patients in the United States initiating 1L single-agent ibrutinib at 420 mg/day (index date) and staying on this dose versus patients with dose adjustment (DA) within 3-12 months. Two databases were used: Komodo claims (a majority from community practices) and Acentrus electronic medical records (from academic and non-teaching hospital systems). To account for immortal time bias (patients with DA survived on 1L therapy until DA) and overlap between follow-up time and definition of treatment strategies, a target trial emulation approach was used, where patients were cloned at index date and contributed follow-up to both treatment strategy arms until deviation from the strategy. Among 3,343 patients in Komodo (mean age: 67.5 years; 37.6% female) and 1,171 patients in Acentrus (mean age: 70.4 years; 34.6% female) who initiated 1L single-agent ibrutinib 420 mg/day, 18.0% and 19.6% had a DA, respectively. DA was not associated with an increased risk of having a next treatment in both databases (adjusted hazard ratio [95% confidence interval]: Komodo: 0.95 [0.80-1.14], Acentrus: 1.14 [0.80-1.62]). These findings suggest that a flexible dosing approach with ibrutinib may be effective in allowing patients to achieve optimal outcomes while remaining on long-term continuous 1L treatment.