Prognostic Impact and Risk Factors of Infections in Patients with Chronic Lymphocytic Leukemia Treated with Ibrutinib
Francesca Romana Mauro, Diana Giannarelli, Andrea Visentin, Gianluigi Reda, Paolo Sportoletti, Anna Maria Frustaci, Annalisa Chiarenza, Stefania Ciolli, Candida Vitale, Luca Laurenti, Lorenzo De Paoli, Roberta Murru, Massimo Gentile, Gian Matteo Rigolin, Luciano Levato, Annamaria Giordano, Giovanni Del Poeta, Caterina Stelitano, Claudia Ielo, Alessandro Noto, Valerio Guarente, Stefano Molica, Marta Coscia, Alessandra Tedeschi, Gianluca Gaïdano, Antonio Cuneo, Robin Foà, Maurizio Martelli, Corrado Girmenia, Giuseppe Gentile, Livio Trentin
Abstract
Ibrutinib represents extraordinary progress in the treatment of chronic lymphocytic leukemia (CLL). However, treatment-related adverse events limit the benefit of this agent. This observational, multicenter study focused on the incidence, risk factors, and prognostic impact of infections in 494 patients with CLL treated with an ibrutinib-based treatment. Ibrutinib was given to 89 (18%) previously untreated patients (combined with rituximab, 24) and 405 (82%) relapsed/refractory patients. Pneumonia (PN), grade ≥3 non-opportunistic infections (NOI), and opportunistic infections (OI) were recorded in 32% of patients with an overall incidence rate per 100 person-year of 15.3% (PN, 10%; NOI, 3.3%; OI, 2%). Infections were the reason for the permanent discontinuation of ibrutinib in 9% of patients. Patients who experienced pneumonia or a severe infection showed a significantly inferior survival than those who were infection-free (p < 0.0001). A scoring system based on the three factors associated with a significant and independent impact on infections—PN or severe infection in the year before starting ibrutinib, chronic obstructive pulmonary disease, ≥2 prior treatments—identified patients with a two- to threefold increase in the rate of infections. In conclusion, the results of this study highlight the adverse impact of infectious events on the outcomes of CLL patients treated with ibrutinib.