PS1264 FRENCH IBRUTINIB OBSERVATIONAL STUDY (FIRE): REAL‐WORLD STUDY OF IBRUTINIB TREATMENT FOR MANTLE CELL LYMPHOMA (MCL) IN FRANCE
Authors: B. Slama, A. Delmer, G. Cartron, B. Anglaret, O. Fitoussi, K. le DÛ, L. Oberic, F. Peyrade, H. Orfeuvre, D. Senecal, L. Molina, C. Albrecht, J. Thevenon, S. Beauclair, C. Kavanagh, S. Le Gouill
Journal: HemaSphere (2019)

Background: Ibrutinib is a first‐in‐class oral inhibitor of Bruton's tyrosine kinase approved for the treatment of adult patients (pts) with MCL who have received ≥1 prior therapy (R/R). In registrational clinical trials (Study 1104 [NCT01236391]; Wang et al. Blood. 2015;126:739–745; MCL3001 [NCT01646021]; Dreyling et al. Lancet. 2016;387:770–778), single‐agent ibrutinib provided durable responses and good progression‐free survival (PFS) and was well tolerated in pts with R/R MCL. The FIRE study was conducted in France to examine real‐world efficacy and safety of ibrutinib in MCL. The first interim analysis (IA) was presented at the 38 th Congress of the Société Française d’Hématologie (March 28–30, 2018, Paris, France). Aims: To assess ibrutinib outcomes in real‐world pts with MCL in France. Methods: This retrospective (ret) and prospective (pro), noninterventional, multicenter study enrolled pts aged ≥18 years with a confirmed diagnosis of R/R MCL who initiated ibrutinib on or after November 21, 2014 (date of commercialization). Pts who initiated ibrutinib after this date but before the study initiation date, May 2016, were retrospectively included. After ibrutinib initiation, pts will be followed for up to 5 years. The primary efficacy end point was PFS; secondary end points included overall survival (OS). This second IA reports baseline characteristics, ibrutinib treatment exposure, efficacy, and safety. Results: Of the 106 pts (47 ret/59 pro) with MCL who received ibrutinib and were included in the IA efficacy population, 41 (38.7%) had received 1 prior line of therapy, 33 (31.1%) 2 prior lines, and 32 (30.3%) ≥3 prior lines. Median age was 74.0 years (range 49.0–88.0 years), and 81.1% were male. Median time from diagnosis to ibrutinib initiation was 4.3 (0.2–25.4) years. In the IA efficacy population, with median follow‐up of 23.7 months, median PFS was 20.0 months (Figure) with PFS rates of 66.8% at 12 months and 42.2% at 24 months. In pts receiving 1, 2, or ≥3 prior lines of therapy, median PFS was 20.0, 19.8, and 17.9 months, respectively. With median follow‐up of 25.6 months, median OS was 29.8 months. In the IA safety population (receiving ≥1 dose of ibrutinib: N = 107), 86.0% of pts received ibrutinib 560 mg at initiation (420 mg, 8.4%) and median exposure was 13.4 months. 32.7% of pts required ≥1 ibrutinib dose modification, and 35.5% had ≥1 temporary discontinuation of ibrutinib. Concomitant antithrombotic treatment was received by 32 (30.2%) pts. At least 1 treatment‐emergent adverse event (TEAE) of any grade was reported in 99.1% of pts; TEAEs were related to ibrutinib in 69.2% of pts and TEAEs resulting in drug withdrawal in 32.7% of pts. Serious TEAEs of any grade were reported in 68.2% of pts (related to ibrutinib in 19.6% of pts). The most common TEAEs of interest of any grade were infection (36.4%), diarrhea (20.6%), arthralgia (12.1%), atrial fibrillation (10.3%), rash (6.5%), hypertension (5.6%), and myalgia (1.9%). At least 1 bleeding TEAE was reported in 34.6% of pts overall and in 50.0% of pts receiving concomitant antithrombotic therapy. 6.5% of pts experienced ≥1 major bleeding TEAE. Summary/Conclusion: FIRE is the first real‐world study of ibrutinib use in clinical practice in France. The data collected in R/R MCL reflect ibrutinib efficacy and safety in clinical trials. Response and outcome data are in line with previous reports and no new safety signals were identified. image