Invasive fungal infection incidence and risk factors in patients receiving ibrutinib in real‐life settings: A nationwide population‐based cohort study

Author:

Allouchery Marion123ORCID,Brunet Kévin245ORCID,Tomowiak Cécile67,Singier Allison3ORCID,Pambrun Elodie3,Pariente Antoine3,Bezin Julien38,Pérault‐Pochat Marie‐Christine19,Salvo Francesco38

Affiliation:

1. Pharmacologie Clinique et Vigilances CHU de Poitiers Poitiers France

2. Faculté de Médecine et de Pharmacie Université de Poitiers Poitiers France

3. Univ. Bordeaux, INSERM, BPH, U1219, Team AHeaD Bordeaux France

4. INSERM U1070 PHAR2 Université de Poitiers Poitiers France

5. Laboratoire de Parasitologie et Mycologie Médicale CHU de Poitiers Poitiers France

6. Onco‐Hématologie et Thérapie Cellulaire CHU de Poitiers Poitiers France

7. INSERM CIC 1402 CHU de Poitiers Poitiers France

8. CHU de Bordeaux, Pôle de Santé Publique, Service de Pharmacologie médicale Bordeaux France

9. Laboratoire de Neurosciences Expérimentales et Cliniques, INSERM, UMR1084 Université de Poitiers Poitiers France

Abstract

AbstractBackgroundData on the risk of invasive fungal infections (IFI) with ibrutinib treatment are scarce.ObjectivesThis study aimed to determine IFI incidence and risk factors in ibrutinib‐treated patients in real‐life settings.MethodsWe constituted a cohort of ibrutinib incident users in the French National Healthcare Database. All patients ≥18 years with a first dispensing of ibrutinib between 21 November 2014 and 31 December 2019 were included. Patients were followed from the cohort entry date until IFI, ibrutinib discontinuation, death, or 31 December 2020, whichever came first. The cumulative incidence function method was used to estimate the probability of IFI accounting for competing risk of death. A multivariate cause‐specific Cox proportional hazards model was used to assess independent IFI risk factors.ResultsAmong 6937 ibrutinib‐treated patients, 1‐year IFI cumulative incidence was 1.3%, with invasive aspergillosis being the most frequent. Allogenic or autologous stem cell transplantation (ASCT) (hazard ratio [HR] 3.59, 95% confidence interval [1.74; 7.41]), previous anticancer treatment (HR 2.12, CI 95% [1.34; 3.35]) and chronic respiratory disease (HR 1.66, [1.03; 2.67]) were associated with higher risk of IFI. Besides neutropenia and corticosteroids, use of anti‐CD20 agents was significantly more frequent in patients having experienced IFI (HR 3.68, [1.82; 7.45]).ConclusionsIn addition to patients with ASCT history, severe neutropenia or treated with corticosteroids, our findings support active surveillance of IFIs in those with chronic respiratory disease, previously treated, or treated with anti‐CD20 agents in combination with ibrutinib. Further studies are needed to optimise IFI prophylaxis in these patient subgroups.

Publisher

Wiley

Subject

Infectious Diseases,Dermatology,General Medicine

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