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Early-onset invasive aspergillosis and other fungal infections in patients treated with ibrutinib

David Ghez, Anne Calleja, Caroline Protin, Marine Baron, Marie-Pierre Ledoux, Gandhi Damaj, Mathieu Dupont, Brigitte Dreyfus, Emmanuelle Ferrant, Charles Herbaux, Kamel Laribi, Ronan Le Calloch, Marion Malphettes, Franciane Paul, Laetitia Souchet, Malgorzata Truchan-Graczyk, Karen Delavigne, Caroline Dartigeas and Loïc Ysebaert

Key points

  • Ibrutinib may be associated with invasive fungal infections especially invasive aspergillosis

  • Most infections usually occur during the first months of treatment, often in patients with other risk factors for fungal infections

Abstract

Ibrutinib has revolutionized the management of chronic lymphocytic leukemia and is now being increasingly used. Although considered to be less immunosuppressive than conventional immunochemotherapy, the observation a few cases of invasive fungal infections in patients treated with ibrutinib prompted us to conduct a retrospective survey. We identified 33 cases of invasive fungal infections in patients receiving ibrutinib alone or in combination. Invasive aspergillosis was overrepresented (27/33) and was associated with cerebral localizations in 40% of the cases. Remarkably, most cases of invasive fungal infections occurred with a median of 3 months after starting ibrutinib. In 18/33 cases, other conditions that could have contributed to decreased antifungal responses, such as corticosteroids, neutropenia or combined immunochemotherapy, were present. These observations indicate that ibrutinib may be associated with early-onset invasive fungal infections, in particular invasive aspergillosis with frequent cerebral involvement, and that patients on ibrutinib should be closely monitored in particular when other risk factors of fungal infections are present.

  • Submitted November 27, 2017.
  • Accepted January 20, 2018.