Fungal infections in patients treated with ibrutinib: two unusual cases of invasive aspergillosis and cryptococcal meningoencephalitis

Ibrutinib‐associated invasive fungal diseases in patients with chronic lymphocytic leukaemia and non‐Hodgkin lymphoma: An observational study

“…To date, the present study is the largest international, multicentre cohort of patients reported, supporting many of the findings of the French study such as a male predominance, an underlying diagnosis of CLL in the majority of patients, with a notable high percentage of CLL patients with high‐risk features (17p deletions or TP53 mutations) but few with neutropenia. Aspergillus spp was the most common pathogens, with frequent CNS dissemination, similar to other reports . In the current cohort symptoms of IFD symptoms ensued shortly after initiating treatment with ibrutinib, in some as early as one day and in 59% of cases within two months.…”

“…Aspergillus spp was the most common pathogens, with frequent CNS dissemination, similar to other reports. 3,4,6,9,10,12,14,17,25,26 In the current cohort symptoms of IFD symptoms ensued shortly after initiating treatment with ibrutinib, in some as early as one day and in 59% of cases within two months. The number of reports of IFD, particularly moulds, following closely upon the initiation of treatment with ibrutinib is increasing.…”

“…Most patients in the current study (86%) were not neutropenic in appropriate anti-fungal therapy, mortality was extremely high (69%) in comparison to 39% of patients in the pre-ibrutinib era. 21 Ibrutinib-associated IFD have been described in several case reports and series of patients, 6,[9][10][11][12][13][14]16,17,19,24 the largest originated in France and included 33 patients (Table 3). 6 To date, the present study is the largest international, multicentre cohort of patients reported, supporting many of the findings of the French study such as a male predominance, an underlying diagnosis of CLL in the majority of patients, with a notable high percentage of CLL patients with high-risk features (17p deletions or TP53 mutations) but few with neutropenia.…”

“…Thereafter, an increasing number of reports of IFD and other opportunistic infections during ibrutinib treatment have been published, with Aspergillus species, being the most frequent pathogens . Epidemiological data concerning fungal infections in patients with lymphoproliferative disorders are scarce and are mainly based on the Italian SEIFEM‐2004 study which reported an annual incidence of invasive moulds and yeast infections of 0.4% and 0.1%, respectively, for CLL and 0.9% and 0.7%, respectively, for NHL…”

“…7 Thereafter, an increasing number of reports of IFD and other opportunistic infections during ibrutinib treatment have been published, with Aspergillus species, being the most frequent pathogens. 6,[8][9][10][11][12][13][14][15][16][17][18][19][20] Epidemiological data concerning fungal infections in patients with lymphoproliferative disorders are scarce and are mainly based on the Italian SEIFEM-2004 study which reported an annual incidence of invasive moulds and yeast infections of 0.4% and 0.1%, respectively, for CLL and 0.9% and 0.7%, respectively, for NHL. 21 This retrospective, multi-national survey was undertaken to add a systematic collection of data to the accumulating reports of ibrutinib-associated IFD in CLL and NHL patients and to determine the prevalence and clinical features of IFD in this setting.…”