FIRE Study: Real-World Effectiveness and Safety of Ibrutinib in Clinical Practice in Patients with CLL and MCL

Abstract

The FIRE study investigated the real-world effectiveness and safety of ibrutinib in prospectively observed patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and mantle cell lymphoma (MCL) in France. Patients were mostly relapsed/refractory with high-risk features. First-line CLL/SLL patients had del17p and/or TP53 mutations. In this interim analysis, the median follow-up time for patients with CLL/SLL and MCL was 17.7 and 15.1 months, respectively. In the effectiveness populations for CLL/SLL (n = 200) and MCL (n = 59), the median progression-free survival was not estimable and 12.4 months, respectively; the 12-month overall survival rates were 88.5% and 65.8%, respectively. Treatment-emergent adverse events of interest for patients with CLL/SLL (n = 202) and MCL (n = 59) included: infections and infestations (53.5% and 32.2%), major bleeding (5.0% and 5.1%), and atrial fibrillation (5.9% and 8.5%); 135 (66.8%) and 20 (33.9%) patients were continuing treatment at the time of data cutoff. Future analyses will report on longer-term follow-up (Trial registration: ClinicalTrials.gov, NCT03425591. Registered 1 February 2018—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03425591).

Outcomes with ibrutinib in patients with chronic lymphocytic leukaemia: Results from the German multicentre REALITY study

“…However, retention rates were comparable with those observed in the real‐world evidence FIRE study for patients with relapsed/refractory CLL (66.8% at ~17 months) 28 and another real‐world study of patients with previously untreated CLL (81% at 1 year) 29 . In REALITY, the most common reason for permanent treatment discontinuation was because of AEs (33% overall), which is consistent with data seen in previous real‐world studies 28‐31 . Compared with the number of patients who discontinued ibrutinib treatment ( n = 127), not many reinitiated their next line of therapy ( n = 66).…”

“…Within the REALITY study, overall retention rates (overall 69.9%; 1L 77.9% at 1 year) were generally lower than those observed in randomized controlled trials for previously untreated patients, such as RESONATE‐2 (87% at ~18 months), 1 CAPTIVATE (92% at ~15 months) 15 and an ibrutinib + rituximab trial (78.8% at ~34 months) 13 . However, retention rates were comparable with those observed in the real‐world evidence FIRE study for patients with relapsed/refractory CLL (66.8% at ~17 months) 28 and another real‐world study of patients with previously untreated CLL (81% at 1 year) 29 . In REALITY, the most common reason for permanent treatment discontinuation was because of AEs (33% overall), which is consistent with data seen in previous real‐world studies 28‐31 .…”

“…29 In REALITY, the most common reason for permanent treatment discontinuation was because of AEs (33% overall), which is consistent with data seen in previous realworld studies. [28][29][30][31] Compared with the number of patients who discontinued ibrutinib treatment (n = 127), not many reinitiated their next line of therapy (n = 66). This suggests that many patients benefited from ibrutinib even though therapy had been discontinued, as alternative treatment is not always needed after stopping continuous ibrutinib, particularly if CLL is in remission.…”

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

“…deletion (del)17p or TP53 mutation; unmutated immunoglobulin heavy chain (IGHV) genes). Results of the second and third interim analyses were previously reported [13,14]. In the second interim analysis, with a median follow-up of 17.4 months, the ndings con rmed effectiveness in R/R patients with high-risk features and did not highlight additional adverse events (AE) than those documented in clinical trials [13,15].…”

“…Results of the second and third interim analyses were previously reported [13,14]. In the second interim analysis, with a median follow-up of 17.4 months, the ndings con rmed effectiveness in R/R patients with high-risk features and did not highlight additional adverse events (AE) than those documented in clinical trials [13,15]. In the third interim analysis, with a median follow-up of 47.2 months, the results showed that ibrutinib was still an effective treatment for CLL patients and that patients who have received ibrutinib in earlier line of treatment had a better PFS [14].…”