Ibrutinib as first line therapy in chronic lymphocytic leukemia patients over 80 years old: A retrospective real‐life multicenter Italian cohort

• Published in: Hematological oncology 2024-01, Vol.42 (1), p.e3249-n/a
• Main Authors: Martino, Enrica Antonia, Mauro, Francesca Romana, Reda, Gianluigi, Laurenti, Luca, Visentin, Andrea, Frustaci, Annamaria, Vigna, Ernesto, Pepe, Sara, Catania, Gioacchino, Loseto, Giacomo, Murru, Roberta, Chiarenza, Annalisa, Sportoletti, Paolo, Principe, Maria Ilaria, Laureana, Roberta, Coscia, Marta, Galimberti, Sara, Ferretti, Eleonora, Zucchetto, Antonella, Bomben, Riccardo, Polesel, Jerry, Tedeschi, Alessandra, Rossi, Davide, Trentin, Livio, Neri, Antonino, Morabito, Fortunato, Gattei, Valter, Gentile, Massimo
• Format: Article
• Language: English
• Subjects: Adenine - analogs & derivatives; Aged, 80 and over; Anemia; Bleeding; Chromosome 17; Chronic lymphocytic leukemia; Clinical trials; Congestive heart failure; elderly; Gene deletion; Humans; Hypertension; ibrutinib; Italy; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell - pathology; Malignancy; Neutropenia; p53 Protein; Pharmacology; Piperidines; Retrospective Studies; Survival; Therapy; Treatment Outcome
• ISSN: 0278-0232; 1099-1069
• DOI: 10.1002/hon.3249

Although chronic lymphocytic leukemia (CLL) predominantly affects the elderly, limited data exists about the outcomes of over 80‐year‐old patients, usually underrepresented in clinical trials. We conducted a multicenter study enrolling 79 consecutive CLL patients ≥80 years at the time of frontline therapy, all treated with ibrutinib. Nearly 48% of cases exhibited unmutated IGHV genes, 32% 17p deletion, and 39.2% TP53 mutations; 63.3% displayed a cumulative illness rating scale (CIRS) > 6. The overall response rate on ibrutinib, computed in 74/79 patients (5 patients excluded for early withdrawal), was 89.9%. After a median follow‐up of 28.9 months, the median progression‐free survival (PFS) and overall survival (OS) were 42.5 and 51.8 months, respectively. CIRS>6 and temporary discontinuation of ibrutinib lasting for 7–30 days were the only parameters associated with a significantly shorter PFS and were both relevant in predicting a shorter PFS compared to patients with CIRS≤6 and therapy discontinuation ≤7 days. The most common grade≥3 adverse events were infections (25.5%), neutropenia (10.1%), and anemia (2.5%). Eighteen patients (22.8%) experienced a cardiovascular event, including grade‐2 atrial fibrillation (n = 9; 11%), grade‐2 hypertension (n = 5; 6%), heart failure (n = 3; 3%), and acute coronary syndrome (n = 1; 1%). Mild bleeding events were observed in 27 patients (34.2%). Ibrutinib was permanently discontinued in 26 patients due to progressive disease (n = 11, including 5 Richter's syndromes), secondary malignancies (n = 6), infections (n = 3), cardiac failure (n = 3), severe bleeding (n = 2), and sudden death (n = 1). In conclusion, our analyses confirmed the overall effectiveness and favorable safety profile of the ibrutinib‐single agent therapeutic approach in CLL patients ≥80 years.