FIRE is a noninterventional, multicenter observational trial of patients in France receiving ibrutinib for the treatment of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). For a study, researchers sought to gather empirical data to define ibrutinib treatment patterns and evaluate the drug’s efficacy and safety in CLL/SLL.

The start date for the retrospective (ret) and prospective (pro) study was May 12, 2016, and its anticipated completion date is 6 years. Patients who began taking ibrutinib therapy on or after November 21, 2014—the date of ibrutinib commercialization—and who had a confirmed diagnosis of CLL or SLL, as well as those who were ≥18 years, had a del17p and/or TP53 mutation, or who had relapsed or refractory disease R/R—were eligible. Within 30 days of the study’s commencement, pro patients began taking ibrutinib. Before enrollment in the study, ret patients began their ibrutinib medication more than 30 days earlier. Progression-free survival (PFS) was the primary outcome indicator; other indicators were overall response rate (ORR), overall survival (OS), time to next treatment (TTNT), and safety. Ibrutinib-related adverse events (AEs) were the only ones in RET-collected AEs, but ALL treatment-emergent AEs (TEAEs) were included in PRO-collected AEs. Consequently, AEs are reported individually for each group. Results for total population efficacy were left-truncated. Patients were cared for in accordance with customary regional clinical practice.

With a median follow-up of 47.2 months and an emphasis on subgroup analysis, we provide the findings from the third interim analysis for patients with previously untreated and R/R CLL/SLL. There were 394 patients (pro, n = 200; ret, n = 194) and 400 patients (pro, n = 202; ret, n = 198) in each of the effectiveness and safety populations, respectively. Ibrutinib was effectiveness and safety population, 39.0-93.0); 66.2% of patients were male; and the median time from diagnosis to Ibrutinib start was 7 years (range, 0.0-35.0). Patients had either 0 (15.0%), 1, 36.3%, 2, or ≥3 (20.6%) previous lines of treatment (LOT). A complete response (CR; 50.0%) or partial response (PR; 36.2%) to the most recent therapy was noted at the baseline. The majority of patients (87.4%) progressed after their last course of treatment, and the median time from progression to the start of ibrutinib was 2.1 months (range, 0.0-100.1). The most frequent justification (42.6%) for starting ibrutinib treatment among reported patients (n = 399) was massive or symptomatic lymphadenopathy and/or splenomegaly. The median PFS was 47.5 months (in pro/ret, it was 48.5/51.6 months). Age (≤75 years vs >75 years) and LOT were statistically significant predictors of PFS. The median PFS was not estimable (NE), 53.9 months, 47.5 months, and 33.5 months, respectively, in patients with 0, 1, 2, and ≥3 previous LOTs. ORR was 91.4% after a follow-up of 48 months. The median TTNT was 54.6 (NE/54.8 in pro/ret) months. In both pro/ret cohorts and overall, the median OS was NE. In the pro/ret cohorts, serious TEAEs associated with ibrutinib were recorded in 25.8% and 28.2/23.2%, respectively. In the pro/ret cohorts, AEs resulted in dosage stoppage (37.6/29.8%), withdrawal (30.2/22.7%), or decrease (26.7/11.1%). Infection (68.8/57.1%), diarrhea (27.2/15.7%), arthralgia/myalgia (25.2/13.1%), arrhythmia (15.8/13.6% [including atrial fibrillation 9.4%/7.1%]), hypertension (14.9/14.6%), rash (10.4/8.1%), and significant bleeding (7.9/1.5%) were the TEAEs of concern in the pro/ret cohorts. In 234 individuals (58.5%), ibrutinib was permanently stopped; the most common causes (n = 212) were AEs (36.8%) and disease progression (31.1%).

Ibrutinib was demonstrated to be an effective treatment for patients with CLL/SLL in the longer follow-up of the real-world FIRE study reflecting clinical practice in France, and patients who received ibrutinib in earlier LOT achieved better PFS. Clinical study findings were consistent with the efficacy and adverse event patterns.