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- Title
Severe infections requiring intensive care unit admission in patients receiving ibrutinib for hematological malignancies: a groupe de recherche respiratoire en réanimation onco-hématologique (GRRR-OH) study.
- Authors
Baucher, Louise; Lemiale, Virginie; Joseph, Adrien; Wallet, Florent; Pineton de Chambrun, Marc; Ferré, Alexis; Lombardi, Romain; Platon, Laura; Contejean, Adrien; Fuseau, Charline; Calvet, Laure; Pène, Frédéric; Kouatchet, Achille; Mokart, Djamel; Azoulay, Elie; Lafarge, Antoine
- Abstract
Background: In the last decade, Ibrutinib has become the standard of care in the treatment of several lymphoproliferative diseases such as chronic lymphocytic leukemia (CLL) and several non-Hodgkin lymphoma. Beyond Bruton tyrosine kinase inhibition, Ibrutinib shows broad immunomodulatory effects that may promote the occurrence of infectious complications, including opportunistic infections. The infectious burden has been shown to vary by disease status, neutropenia, and prior therapy but data focusing on severe infections requiring intensive care unit (ICU) admission remain scarce. We sought to investigate features and outcomes of severe infections in a multicenter cohort of 69 patients receiving ibrutinib admitted to 10 French intensive care units (ICU) from 1 January 2015 to 31 December 2020. Results: Median time from ibrutinib initiation was 6.6 [3–18] months. Invasive fungal infections (IFI) accounted for 19% (n = 13/69) of severe infections, including 9 (69%; n = 9/13) invasive aspergillosis, 3 (23%; n = 3/13) Pneumocystis pneumonia, and 1 (8%; n = 1/13) cryptococcosis. Most common organ injury was acute respiratory failure (ARF) (71%; n = 49/69) and 41% (n = 28/69) of patients required mechanical ventilation. Twenty (29%; n = 20/69) patients died in the ICU while day-90 mortality reached 55% (n = 35/64). In comparison with survivors, decedents displayed more severe organ dysfunctions (SOFA 7 [5–11] vs. 4 [3–7], p = 0.004) and were more likely to undergo mechanical ventilation (68% vs. 31%, p = 0.010). Sixty-three ibrutinib-treated patients were matched based on age and underlying malignancy with 63 controls receiving conventional chemotherapy from an historic cohort. Despite a higher median number of prior chemotherapy lines (2 [1–2] vs. 0 [0–2]; p < 0.001) and higher rates of fungal [21% vs. 8%, p = 0.001] and viral [17% vs. 5%, p = 0.027] infections in patients receiving ibrutinib, ICU (27% vs. 38%, p = 0.254) and day-90 mortality (52% vs. 48%, p = 0.785) were similar between the two groups. Conclusion: In ibrutinib-treated patients, severe infections requiring ICU admission were associated with a dismal prognosis, mostly impacted by initial organ failures. Opportunistic agents should be systematically screened by ICU clinicians in this immunocompromised population.
- Subjects
FRANCE; OPPORTUNISTIC infections; INTENSIVE care units; STATISTICS; RESEARCH; RESPIRATORY insufficiency; CRITICALLY ill; PNEUMOCYSTIS pneumonia; CRYPTOCOCCOSIS; CANCER chemotherapy; EARLY warning score; MULTIVARIATE analysis; ANTINEOPLASTIC agents; RETROSPECTIVE studies; PATIENTS; QUANTITATIVE research; MANN Whitney U Test; FISHER exact test; TREATMENT duration; SEVERITY of illness index; PROTEIN-tyrosine kinase inhibitors; TREATMENT effectiveness; CANCER patients; QUALITATIVE research; ASPERGILLOSIS; ARTIFICIAL respiration; HOSPITAL mortality; COMPARATIVE studies; HOSPITAL care; HEMATOLOGIC malignancies; SYMPTOMS; DESCRIPTIVE statistics; MYCOSES; VIRUS diseases; KAPLAN-Meier estimator; LYMPHOPROLIFERATIVE disorders; DATA analysis software; ALGORITHMS; LONGITUDINAL method; ACUTE diseases; DISEASE complications
- Publication
Annals of Intensive Care, 2023, Vol 13, Issue 1, p1
- ISSN
2110-5820
- Publication type
Article
- DOI
10.1186/s13613-023-01219-5