P116 | OUTCOMES OF PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA TREATED WITH DOSE-ADJUSTMENT IBRUTINIB: A MONOCENTER-REAL-LIFE STUDY

Background: Clinical studies show IBR's safety and efficacy, but real-world data reveal increased toxicity and interruption rates. Adverse event (AE)-related interruptions occur in 14–29% of cases in clinical practice, compared to 4–9% in Phase III studies. Dose adjustments (DA) in real life are also more frequent (10–31% vs 9%). Temporary interruptions can negatively affect progression-free survival (PFS) and overall survival (OS), while clinically guided DA have minimal effects on PFS and OS. Flexible ibrutinib (IBR) dosing could help reduce AEs while preserving treatment efficacy. Methods: We conducted a retrospective study of 100 chronic lymphocytic leukemia (CLL) patients (pts) treated with IBR from Jan 2016 to Dec 2022. Pts were categorized into 2 groups: standard dosing (SD, 420 mg) and dose-adjusted (DA, 280 mg or 140 mg) based on AEs or drug interactions. Pts were categorized by biological characteristics, disease stage, and comorbidities, forming 2 groups: standard dosing (SD) (420 mg) and DA (280 mg or 140 mg). Aims: to assess PFS and time to next treatment (TTNT). Results: Eight-five pts (median age 64, range 57–90; M/F 64%/36%, 45% with at least 1 comorbidity started IBR at the SD of 420 mg, while 15 at DA (13 at 280 mg and 2 at 140 mg) due to drug interactions. The 2 groups were balanced in terms of biological characteristics, clinical stage, and performance status. Overall response rate was 71% complete remission (CR), 28% partial response (PR), 1% disease progression (PD), with best response at median 10.6 months. First DA occurred in 43% of patients after a median of 10 months. Atrial fibrillation caused 23% of first DAs. Among those with AE-related DA, 25.5% required further DA due to new AEs (an average of 9.7 months later) and 31% experienced recurrence of the initial AE. Treatment was temporarily discontinued in 29% (median 61 days) and permanently stopped in 19%.After a median follow-up of 84 months, 5-year PFS was 66.6% (SD) vs 63.8% (DA), p=0.45; 5-year TTNT was 66.7% (SD) vs 83.8% (DA), p=0.22 (Figure). Conclusions: Our real-world study confirms higher DA and discontinuation rates compared to clinical trials. Despite the limited sample, DA seem not negatively impact on PFS or TTNT, supporting the role of flexible dosing as strategy to manage toxicity while maintaining long-term efficacy. This observation is mainly relevant for very elderly pts or those with comorbidities.