P123 | IBRUTINIB AND VENETOCLAX IN CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS OUTSIDE CLINICAL TRIALS: A SINGLE-CENTER REAL-WORLD EXPERIENCE

Introduction: The combination of ibrutinib, a Bruton's tyrosine kinase inhibitor, and venetoclax, a BCL-2 inhibitor, has shown synergistic efficacy in chronic lymphocytic leukemia (CLL). Pivotal trials like CAPTIVATE and GLOW report high rates of complete remission (CR) and undetectable minimal residual disease (uMRD) in over 70% of patients. Methods: A retrospective analysis was performed on 11 treatment-naive (TN) CLL patients who started ibrutinib and venetoclax (I-V) as first-line therapy between March 2024 and April 2025 at our institution, outside clinical trials. Biological and clinical data were collected at baseline. Tumor lysis syndrome (TLS) risk was assessed based on lymphocyte count and lymph node size. The treatment protocol followed international guidelines, beginning with ibrutinib lead-in followed by venetoclax ramp-up. Response was evaluated at 6 months. Safety data were also analyzed according CTCAE. Results: The median age at treatment initiation was 55 years (range: 49-70). TP53 mutations were not detected in any of the 10 patients for whom data were available; IGHV was mutated in 6 patients (60%). FISH analysis showed no cases of del(17p). At baseline, 7 patients (64%) had limited disease (Rai stage I-II) and 4 (36%) had advanced disease (Rai stage III-IV). According to Binet staging, 1 patient (9%) was stage A, 6 (55%) were stage B, and 4 (36%) were stage C. Eight patients (73%) had intermediate TLS risk, and 3 (27%) had high risk. The median treatment duration at data analysis was 6 months. Among the 6 patients who received at least 6 months of treatment, 5 (83%) achieved CR, and 1 (17%) achieved partial remission (PR). Although MRD was not formally assessed, clinical and radiological responses suggested deep remissions in all CR cases. The treatment was well tolerated. Adverse events included grade 2 thrombocytopenia in 1 patient (9%), grade 2 neutropenia in 1 (9%), grade 3 neutropenia in 1 (9%), grade 3 infectious diarrhea in 1 (9%), and grade 1 headache in 1 (9%). No cases of febrile neutropenia, atrial fibrillation, or hypertension were observed. No severe adverse events were reported. Conclusion: This small real-world series supports the effectiveness of the I-V combination as first-line therapy in CLL. The high complete remission rate and favorable safety profile suggest its clinical utility. Larger studies with longer follow-up are needed to confirm these findings and assess MRD status and response durability over time.