Prognostic Impact and Risk Factors of Infections in Patients with Chronic Lymphocytic Leukemia Treated with Ibrutinib

SIMPLE SUMMARY: Ibrutinib demonstrated superior efficacy compared to chemoimmunotherapy in patients with chronic lymphocytic leukemia. However, adverse events are a frequent reason for treatment discontinuation. This study was aimed to evaluate the incidence, risk factors, and prognostic impact of infections in a large series of patients with chronic lymphocytic leukemia who received an ibrutinib-based therapy. Approximately one-third of patients developed pneumonia or a severe infection with an overall rate of 15.3% infections per 100 person-year. Patients who experienced a severe infection in the year before starting ibrutinib, those with chronic obstructive pulmonary disease, and those heavily pretreated showed greater vulnerability to infection. A scoring system based on these factors identified patients with a two- to threefold increase in the rate of infections. Infections showed an unfavorable impact in terms of treatment discontinuation and inferior survival. Our results demonstrate that infections are a relevant reason for treatment failure in patients treated with ibrutinib. 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.