Cerebral aspergillosis under ibrutinib therapy: clinical features and management challenges.

BACKGROUND

Ibrutinib is a recognized risk factor for invasive fungal disease (IFD) recognized in the 2019 revised criteria of the European Organisation for Research and Treatment of Cancer. Cerebral aspergillosis (CA) under ibrutinib has been relatively frequently reported, but its particular characteristics remain insufficiently described.

METHODS

The CEREALS study was a nationwide retrospective cohort of 119 patients diagnosed with CA between 2006 and 2018. We analysed 10 patients who developed CA following ibrutinib therapy and compared their clinical, radiological and outcome data with those of other patients with haematological malignancies from this cohort.

RESULTS

Nine patients received ibrutinib for chronic lymphocytic leukaemia and one for diffuse large B-cell lymphoma after a median of two prior treatment lines. None received anti-mould prophylaxis, although 80% of them presented additional IFD risk factors. CA occurred a median of 2.9 months after ibrutinib initiation. All cases resulted from haematogenous dissemination, with extracerebral involvement in 70% of the patients, mostly the lungs. Brain imaging revealed supratentorial abscesses without meningeal involvement in all patients, typically manifesting with focal neurological deficits. Serum galactomannan was positive in 33% of tested patients, exclusively in neutropenic individuals. Six-week mortality was 40%. Compared with other haematological malignancy patients in the CEREALS cohort, ibrutinib-associated CA showed exclusive haematogenous spread, infrequent serum galactomannan positivity and lower mortality (40% versus 62%).

CONCLUSIONS

Cerebral aspergillosis during ibrutinib therapy shows particular features. An invasive microbiological workup is often required, as serum galactomannan appears to have limited sensitivity in this context.