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Treatment with the BTK inhibitor ibrutinib has been an important therapeutic advance for patients with chronic lymphocytic leukemia (CLL) and B-cell non-Hodgkin lymphomas. However, invasive fungal infections have been reported in some patients receiving this agent.
This observation led French investigators to conduct a retrospective multicenter survey of 33 patients with invasive fungal infections who were treated with the drug. Of these, 30 had CLL, 2 had Waldenström macroglobulinemia, and 1 had mantle cell lymphoma. Patients had received a median of 2 prior treatments, and all had received prior immunochemotherapy, but not stem-cell transplantation.
Most patients (27) had aspergillosis, including 11 with central nervous system infection. The other infections were disseminated Cryptococcus (4), mucormycosis (1), and pneumocystis pneumonia (1). Most cases (28) occurred within the first 6 months of ibrutinib therapy, including 20 that occurred within 3 months. Nine patients died from the fungal infection.
Ghez D et al. Early-onset invasive aspergillosis and other fungal infections in patients treated with ibrutinib. Blood 2018 Feb 1; [e-pub]. (http://dx.doi.org/10.1182/blood-2017-11-818286)
Comment
Although the incidence of invasive fungal infections appears to be low overall among ibrutinib-treated patients, it is increased in immunocompromised patients and has been observed with ibrutinib plus immunochemotherapy combination regimens. The mechanisms are unclear but may involve off-target effects of ibrutinib on T-cells or monocyte/macrophage function. Patients need to be informed of this risk, and providers should be vigilant for early diagnosis and therapy.