Final results on effectiveness and safety of Ibrutinib in patients with chronic lymphocytic leukemia from the non-interventional FIRE study
Authors: Dartigeas Caroline , Quinquenel Anne , Ysebaert Loïc , Dilhuydy Marie-Sarah , Anglaret Bruno , Slama Borhane , Le Du Katell , Tardy Stéphanie , Tchernonog Emmanuelle , Orfeuvre Hubert , Voillat Laurent , Guidez Stéphanie , Malfuson Jean-Valère , Dupuis Sandrine , Deslandes Marine , Feugier Pierre , Leblond Véronique ,   on behalf of the FIRE Investigators Group, Adiko Didier , Agape Philippe , Auger Quittet Sophie , Bareau Benoît , Benbrahim Omar , Bernard Philippe , Bescond Charles , Bijou Fontanet , Boudin Laurys , Cailleres Sylvie , Calmettes Claire , Cartron Guillaume , Costello Régis , David Selva , Delaunay Jacques , Delette Caroline , Dennetiere Sophie , Drenou Bernard , El Yamani Abderrazak , Delmer Alain , Fitoussi Olivier , Fleck Emmanuel , Fleury Joël , Gutnecht Jean , Hacini Maya , Jourdan Éric , Kaphan Régis , Karsenti Jean-Michel , Labourey Jean-Luc , Launay Vincent , Le Calloch Ronan , Leduc Isabelle , Lefrere François , Le Gall Stevan , Le Goff Marielle , Legouffe Éric , Le Gouill Steven , Lepretre Stéphane , Liu Jixing , Luttiau Motard Carine , Moldovan Marius , Molina Lysiane , Moullet Isabelle , Peyrade Frédéric , Quittet Philippe , Re Daniel , Roland Virginie , Roos-Weil Damien , Saad Alain , Saad Hussam , Senecal Delphine , Thannberger Alexia , Thieblemont Catherine , Tournilhac Olivier , Visanica Sorin 
Published: March 2024

We conducted an observational study (FIRE) to understand the effectiveness and safety outcomes of ibrutinib in patients with chronic lymphocytic leukemia (CLL) in France, after a maximum follow-up of five years. Patients were included according to the French marketing authorization in 2016 (i.e. patients with relapsed or refractory CLL or to previously untreated CLL patients with deletion 17p and/or tumor protein p53 mutations unsuitable for chemoimmunotherapy) and could have initiated ibrutinib more than 30 days prior their enrolment in the study (i.e. retrospective patients) or between 30 days before and 14 days after their enrolment (i.e. prospective patients). The results showed that in the effectiveness population (N = 388), the median progression-free survival (PFS) was 53.1 (95% CI: 44.5–60.5) months for retrospective patients and 52.9 (95% CI: 40.3–60.6) months for prospective patients and no difference was shown between the PFS of patients who had at least one dose reduction versus the PFS of patients without dose reduction (p = 0.7971 for retrospective and p = 0.3163 for prospective patients). For both retrospective and prospective patients, the median overall survival was not reached. The most frequent treatment-emergent adverse event of interest was infections (57.6% retrospective; 71.4% prospective). A total of 14.6% of the retrospective patients and 22.4% of the prospective patients had an adverse event leading to death. Our findings on effectiveness were consistent with other studies and the fact that patients with dose reductions had similar PFS than patients without dose reduction is reassuring. No additional safety concerns than those already mentioned in previous studies could be noticed.

Trial registration ClinicalTrials.gov, NCT03425591. Registered 1 February 2018 – Retrospectively registered.