Final results on effectiveness and safety of Ibrutinib in patients with chronic lymphocytic leukemia from the non-interventional FIRE study

• DOI: 10.1007/s00277-024-05666-3
• Publication Date: 2024-03-06T04:35:04Z
• Authors: Caroline Dartigeas; Anne Quinquenel; Loïc Ysebaert; Marie-Sarah Dilhuydy; Bruno Anglaret; Borhane Slama; Katell Le Du; Stéphanie Tardy; Emmanuelle Tchern...; Hubert Orfeuvre; Laurent Voillat; Stéphanie Guidez; Jean-Valère Malfuson; Sandrine Dupuis; Marine Deslandes; Pierre Feugier; Véronique Leblond; ; Didier Adiko; Philippe Agape; Sophie Auger Quittet; Benoît Bareau; Omar Benbrahim; Philippe Bernard; Charles Bescond; Fontanet Bijou; Laurys Boudin; Sylvie Cailleres; Claire Calmettes; Guillaume Cartron; Régis Costello; Selva David; Jacques Delaunay; Caroline Delette; Sophie Dennetiere; Bernard Drenou; Abderrazak El Yamani; Alain Delmer; Olivier Fitoussi; Emmanuel Fleck; Joël Fleury; Jean Gutnecht; Maya Hacini; Éric Jourdan; Régis Kaphan; Jean-Michel Karsenti; Jean-Luc Labourey; Vincent Launay; Ronan Le Calloch; Isabelle Leduc; François Lefrere; Stevan Le Gall; Marielle Le Goff; Éric Legouffe; Steven Le Gouill; Stéphane Lepretre; Jixing Liu; Carine Luttiau Mo...; Marius Moldovan; Lysiane Molina; Isabelle Moullet; Frédéric Peyrade; Philippe Quittet; Daniel Re; Virginie Roland; Damien Roos-Weil; Alain Saad; Hussam Saad; Delphine Senecal; Alexia Thannberger; Catherine Thieble...; Olivier Tournilhac; Sorin Visanica
• Keywords: Real-world evidence; [SDV] Life Sciences [q-bio]; 03 medical and health sciences; 0302 clinical medicine; Ibrutinib; Chronic lymphocytic leukemia; Effectiveness; Safety

Abstract 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.