SP08 | FEASIBILITY OF FIXED-DURATION IBRUTINIB PLUS VENETOCLAX COMBINATION AS TREATMENT IN A VERY FRAIL, COMORBID AND BEDRIDDEN PATIENT WITH PREVIOUSLY UNTREATED CHRONIC LYMPHOCYTIC LEUKEMIA

Introduction: Chronic Lymphocytic Leukemia (CLL) accounts for ~1–1.5% of all malignancies and is the most common adult leukemia in Europe and North America. It shows considerable heterogeneity in outcomes, with 50–70% of patients requiring treatment during the disease course. Standard therapies include BTK inhibitors (ibrutinib, acalabrutinib, zanubrutinib) and the BCL2 inhibitor venetoclax, alone or in combination with anti-CD20 antibodies. Since March 2024, the ibrutinib-venetoclax combination has been reimbursed in Italy as first-line therapy, with proven benefits in Progression Free Survival (PFS) and Time To Next Treatment (TTNT) in the GLOW and CAPTIVATE trials. Case Report: We present a 61-year-old man, heavy smoker, with chronic obstructive pulmonary disease (COPD), type 2 diabetes, ischemic-hypertensive cardiomyopathy, prior myocardial infarction, and multiple strokes (cerebellum, midbrain, pons) resulting in bedridden status, right hemiparesis, and dysphagia. Diagnosed with asymptomatic CLL in 2022, he developed symptomatic progression in Feb 2024, with anemia (Hb 9.6 g/dL), rapid lymphocytosis, bulky lymphadenopathy (7–10 cm), splenomegaly (26 cm), and constitutional symptoms (Rai III/Binet C). Beta-2 microglobulin and LDH were >3× ULN. PET/CT ruled out Richter transformation (SUVmax 6.6). FISH showed trisomy 12 and del(13q); del(17p) and TP53 mutation were negative, IGHV was unmutated. CLL-IPI was 5, ECOG PS 4, CIRS 22. Treatment and Outcome: Liver and kidney function were normal; cardiac evaluation was unremarkable. Given high TLS risk, fixed-duration therapy was started (Tab. 1): ibrutinib for 3 months, associating venetoclax from month 4 (WBC <50 × 10⁹/L), with standard 5-week ramp-up. Continuing his antiplatelet therapy, the patient achieved complete hematologic and radiologic response, is completing therapy without dose reductions or interruptions. No bleeding, TLS, or cardiovascular complications were observed, and MRD assessment in peripheral blood is planned. Conclusion: The ibrutinib-venetoclax combination has shown high efficacy across all CLL patient groups in registration trials. Despite safety concerns limiting its recommendation in the US, this case highlights the feasibility and tolerability of ibrutinib-venetoclax even in highly frail, comorbid patients when carefully managed, supporting its use as a best available first-line option in CLL.