According to a thorough literature, these drugs do not expose patients to an increased risk of infections 13, 14. Agents targeting lymphoid or myeloid cell surface antigens Over the last two decades, there has been increasing interest in developing monoclonal antibodies targeting different surface proteins on cells of lymphoid and myeloid lineages for the treatment of leukemia, lymphoma, and multiple myeloma. 22, 23. For these reasons, the Docosanol risk of infection in patients with CLL and NHL treated with these new kinase inhibitors is higher than the overall risk reported in CLL and NHL populations 24, 25. Evidence supporting the potential for infectious complications by the agents affecting the BCR has been provided mostly by clinical trials where infections (frequently of the respiratory tract) occurred typically at the beginning of treatment and the infection rate declined by more than half after a few months of therapy. However, specific epidemiological studies on infections treated with ibrutinib and idelalisib are scarce and most of the data derived from retrospective studies or from phase II or III clinical trials performed to test the efficacy and overall safety of these therapeutic agents but without detailed information on the infectious complications. An association with pulmonary IA was observed shortly after ibrutinib was licensed for use. Of 127 patients with relapsed or refractory CLL treated with ibrutinib with or without rituximab in a single-center study published in 2015, 33 (26%) discontinued treatment for different reasons. Overall, 14 of them discontinued ibrutinib because of adverse events or death, and in two cases a pulmonary IA was diagnosed 26. Some real-life clinical series of patients who received ibrutinib as first-line or salvage therapy have recently been published along with detailed data on infectious complications. The spectrum of serious infections in 378 patients whose lymphoid malignancies were treated with ibrutinib from 2012 to 2016 at the Memorial Sloan Kettering Cancer Center was retrospectively reviewed 27. Overall, serious infection developed in 43 patients (11.4%), primarily during the first year of ibrutinib treatment, and IFDs were documented in 16 (37.2%). IFDs included proved or probable IA in eight patients and Docosanol a concurrent probable IA and pneumonia in one patient. No patient was receiving an anti-fungal prophylactic regimen at the time of IA. The presence of neutropenia at any time during ibrutinib treatment and receipt of three or more previous anti-tumor regimens were significantly associated with an Docosanol increased risk of severe infection. Specifically, the risk factor of corticosteroid use at any point during ibrutinib treatment was associated with the occurrence of IA. A single-institution retrospective study was carried out to find the type and incidence of opportunistic infections (OIs) during ibrutinib treatment and the characteristics and outcomes associated with risk Rabbit polyclonal to EGFR.EGFR is a receptor tyrosine kinase.Receptor for epidermal growth factor (EGF) and related growth factors including TGF-alpha, amphiregulin, betacellulin, heparin-binding EGF-like growth factor, GP30 and vaccinia virus growth factor. 28. In 566 patients who received ibrutinib from June 2010 to March 2016 (74% of patients affected by CLL), the cumulative incidence of OI was 2.3% at 0.5 years and increased to 4.7% at 5 years. IFDs (mainly IA) accounted for 74% of OIs. In a multivariable analysis of at least three prior treatments (hazard ratio [HR] 2.87, 95% confidence interval [CI] 1.12C7.35; = 0.028), diabetes (HR 3.63, 95% CI 1.50C8.77; = 0.004) and liver disease (HR 7.53, 95% CI 2.14C26.49; = 0.002) retained an independent association with OI development. A multicenter survey aimed at identifying cases of IFD in patients whose CLL was treated with ibrutinib was conducted in France 29. Out of 33 IFDs, 27 were proven, probable, or possible IA with cerebral localization in 40% of cases. Remarkably, 85% of IFDs occurred in the first 6 months after starting ibrutinib and 61% occurred in the first 3 months. This trend suggests the possibility that the risk of IFDs, such as IA, decreases with longer exposure to ibrutinib. In the majority of cases, other factors such as corticosteroids, neutropenia, or combined immunochemotherapy that potentially contributed to decreased anti-fungal responses were present. The phenomenon of the high risk of cerebral localization of IA during ibrutinib therapy was also shown in a phase Ib study of ibrutinib treatment of primary central nervous system (CNS) lymphoma; that study reported a 39% incidence of IA in patients who concurrently received corticosteroids in the absence of neutropenia 30. To assess the role of BTK in the risk of infections, the authors evaluated the outcome of IA by comparing the effect of an experimental infection via pharyngeal aspiration in 26 BTK knockout and 20 wild-type mice. Overall, 27% of BTK Docosanol knockout mice and no wild-type mice died after infection, and more severe lung tissue damage and fungal burden were assessed by histology, indicating a contribution of BTK to the innate immune control of infection. These findings suggest that BTK.