P114 | FACTORS INFLUENCING THE REGIMEN CHOICE FOR FIRST-LINE THERAPY IN CHRONIC LYMPHOCYTIC LEUKEMIA: THE FIRST-CLL STUDY

Treatment options for patients with chronic lymphocytic leukemia (CLL) have significantly increased over the years, and different first-line chemo-free regimens are now available. Selecting the optimal treatment requires careful consideration of multiple factors, including biological risk, side effect profiles, concomitant medications, patient fitness and individual preferences. In the absence of mature head-to-head comparisons, this decision-making process remains complex. The FIRST-CLL study describes the allocation of first-line treatments for CLL in a real-world Italian cohort and explores the relative weight of several parameters – such as clinical-biological characteristics, logistical factors and patient preference - in the regimen selection. We collected data from 133 consecutive patients who started treatment from February 2024 to February 2025 in 9 Italian centers. For each case, the treating physician was asked to score from 1 to 5 the importance of different variables in the treatment choice. Among enrolled patients, 56 (42%) received a Bruton tyrosine kinase inhibitor (BTKi), 46 (35%) ibrutinib plus venetoclax (IV) and 31 (23%) venetoclax plus obinutuzumab (VO). IV was the most prescribed regimen in patients <70 years old (60%). Conversely, BTKi were preferred in patients >80 years old (84%). VO, mainly prescribed to older patients with reliable caregiver support, was avoided when caregiver availability was limited, in which case BTKi was favored. Among patients with TP53 disruption, 73% received zanubrutinib. In patients with a history of cardiac arrhythmias, the regimen not including a BTKi (VO) was favored in 50% of cases. Interestingly, a history of heart failure or a recent major bleeding did not preclude BTKi use, although the number of patients is limited. Among BTKi-treated patients, acalabrutinib was preferred in those on antiplatelet therapy. Figure 1 depicts the impact of each analyzed parameter on treatment selection, according to treating physicians. Prognostic features, routes of administration, therapy duration, patient’s preference, age and comorbidities resulted key factors, while tumor lysis syndrome risk and lymph node size did not significantly affect physicians’ choices. With the limit of subjective judgment of individual physicians, our real-world findings highlight how a range of clinical and logistical factors influence therapeutic decisions in the current Italian scenario for first-line CLL treatment.