Late-onset invasive aspergillosis following acalabrutinib in two patients with chronic lymphocytic leukemia: a case report
Hugo Bes-Berlandier, Bochra Sedaki, Dikélélé Elessa, Pilar Dutari, Anne Calleja, Barbara Foucher, Jazil Hassam, Hassina Guerchouche, Stephane Hernandes, Pierre-Christophe Leoni, Pierre Berger, Ferdinand Willetard, David Delarbre, Philippe Lavrard, Gabriel BrisouAbstract
BTK inhibitors (BTKi) have emerged over the past several years as a cornerstone of treatment for chronic lymphocytic leukemia (CLL). While ibrutinib, a first-generation BTKi, was the first in this therapeutic class associated invasive fungal infections (IFI), recent data also reported an increased risk with acalabrutinib, a second-generation BTKi. Acalabrutinib-associated aspergillosis tends to occur relatively early, often within the first few months after BTKI initiation. We describe two late-onset cases in chronic lymphocytic leukemia occurring 22 months after exposure. One patient had proven aspergillosis with brain abscess and pneumonia, while the other had probable aspergillosis with brain and lung involvement. The two patients discontinued BTKi and only one survived. These observations highlight the sustained IFI risk associated with prolonged BTKi therapy. Finally, these findings support a strategy combining vigilant clinical monitoring with regular serum galactomannan assessment in patients with risk factors such as refractory CLL, neutropenia or structural lung diseases.