Ibrutinib in patients over 80 years old with CLL: a multicenter Italian cohort

Chronic lymphocytic leukemia (CLL) is the most frequent leukemia in Western countries, with an incidence increasing to 30/100 000 per years at an age of >80 years.According to recent International Workshop on Chronic Lymphocytic Leukemia guidelines, symptomatic/active disease requires therapeutic interventions aiming to improve overall survival (OS). 1 Ibrutinib is a first-in-class Bruton tyrosine kinase inhibitor (BTKi) that has changed the treatment paradigm of both treatment-naïve (TN) and relapsed/refractory (R/R) patients.2 This therapeutic option has high rates of responses but also a not neglectable toxicity in the published clinical trials with accurately selected candidate patients.[3][4][5] Few real-world studies regarding patients treated with ibrutinib are available, integrating the information reported by trials, although not focused on patients that are over 80. [6][7][8][9][10] We aimed to retrospectively evaluate ibrutinib in a cohort of older patients with TN or R/R CLL to retrieve real-world information for safety and effectiveness of the drug.We performed a multicenter, national study enrolling 60 consecutive patients diagnosed with TN or R/R CLL who were ≥80 years old, with a median age of 81 years (range, 80-87 years) at ibrutinib start.Patients starting ibrutinib in label from January 2014 to March 2021 were enrolled from 6 Italian sites (Table 1).Second-generation BTKis were not available as compassionate use or in clinical trials.The median observation period was 27 months, with a maximum of 87.7 months.The study was approved by the Istituto di Ricerca e Cura a Carattere Scientifico Ca' Granda Ospedale Maggiore Policlinico and was conducted according to the Declaration of Helsinki.A total of 13 patients (21.7%) achieved nodal complete response (CR; bone marrow evaluation not performed), 40 (66.7%)achieved partial response (PR; 88.3% overall response rate), and 7 (11.6%)achieved stable disease (SD).Discontinuation because of progressive disease (PD) occurred mostly in R/R patients and in 1 TN patient, whereas discontinuation because of toxicity occurred in 8 R/R patients and 6 TN patients.Median progression-free survival (PFS) was 51.8 months (95% confidence interval [CI]: 47.4-56.2),and median OS was 53.2 months (95% CI: 43.3-63.0),as most patients died after PD.Patients achieving a response during ibrutinib experienced a prolonged PFS compared with patients achieving SD (P < .0001).A median PFS of 69.7 months (95% CI: 46.1-93.2) was achieved in patients not experiencing temporary drug withholding (7-30 days), whereas patients who had drug interruptions had a median PFS of 49.7 months (95% CI: 35.4-63.9;P = .079);a total of 10 patients (28.6%) among the 35 patients who did not temporarily suspended ibrutinib then permanently discontinued the drug, and among the 25 patients experiencing drug withholdings, 19 patients (76%) discontinued treatment (Figure 1).