P118 | REAL-WORLD OUTCOMES IN CHRONIC LYMPHOCYTIC LEUKEMIA: A 12-YEAR SINGLE-CENTER EXPERIENCE

Introduction Over the past decade, therapeutic strategies for Chronic Lymphocytic Leukemia (CLL) have undergone a profound transformation, shifting from chemoimmunotherapy to targeted agents. Personalized treatment approaches based on clinical and molecular features have been standardized, particularly in elderly and those with comorbidities. However, real-world data on treatment sequencing and outcomes are still limited and sometimes controversial. Methods We conducted a retrospective, single-center, real-world study on 230 consecutive CLL patients treated at the Hematology and Transplant Center, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, Salerno, Italy, between July 2011 and June 2023. Patients received a diagnosis of CLL according to international guidelines, and treatment was initiated based on iwCLL criteria. Therapeutic decisions were individualized, considering clinical status, comorbidities, cytogenetics, molecular profile, and patient preference. First-line therapy was administered in 51% of patients: 65% of them received standard chemoimmunotherapy, while 35% of cases were treated with targeted agents (mainly ibrutinib, or venetoclax+obinutuzumab). A second line treatment was required in 31% of patients. Hematologic responses were evaluated as per iwCLL criteria. Follow-up included flow cytometry immunophenotyping monitoring every 3-6 months. Outcomes were time-to-treatment initiation (TTI), time to next treatment (TTNT), progression-free survival (PFS), and overall survival (OS). Results Patients treated with standard chemoimmunotherapy showed a higher overall response rate (ORR) in first-line settings (70%) compared to those treated with targeted agents (30%), although a trend toward improved OS was observed in patients receiving targeted therapies. CD38 and CD49d expression emerged as relevant prognostic factor, as their co-expression was significantly associated with shorter PFS, particularly in patients treated with BTKi or BCL2i. Conversely, a CD38-CD49d- immunophenotype was linked to a favorable prognosis and significantly higher 5-year OS in patients receiving targeted therapies compared to chemoimmunotherapy (100% vs. 46%; p=0.0181). Conclusion Our real-world data confirm the importance of integrating clinical, biological, and immunophenotypic markers, like CD38 and CD49d, to guide personalized treatment strategies in CLL, even in elderly and/or frail patients, optimizing outcomes in routinely clinical practice.