PF494 CLINICAL OUTCOMES WITH SINGLE‐AGENT IBRUTINIB FOR RELAPSED/REFRACTORY (R/R) MANTLE CELL LYMPHOMA (MCL): INTERIM ANALYSIS (IA) OF THE BELGIAN IBRUTINIB REAL‐WORLD DATA (BIRD) STUDY

Background: MCL is an aggressive B‐cell hematologic malignancy with poor prognosis. Approval of single‐agent ibrutinib, a first in class, once daily oral inhibitor of Bruton's tyrosine kinase, for R/R MCL was based on the high overall response rate (ORR) and sustained activity observed in a phase 2, open‐label, single‐arm trial (Study 1104 [NCT01236391]; Wang et al. Blood. 2015;126:739–745), and improved progression‐free survival (PFS) and tolerability vs temsirolimus in a phase 3, randomized controlled trial (MCL3001 [NCT01646021]; Dreyling et al. Lancet. 2016;387:770–778). Real‐world (RW) studies provide valuable insights into ibrutinib effectiveness and safety in routine clinical practice. Aims: To assess ibrutinib outcomes in RW patients (pts) with MCL in Belgium. Methods: BiRD is a multicenter, observational study of pts with a confirmed diagnosis of MCL, chronic lymphocytic leukemia, or Waldenström's macroglobulinemia who were eligible for ibrutinib reimbursement at treatment initiation (70–80%), or who participated in a Medical Need Program and switched to reimbursed treatment (20–30%). Data were collected both prospectively (pro) and retrospectively (ret). This IA is based on pts with MCL in the evaluable population with ≥12 months of treatment follow‐up (or who discontinued ibrutinib within the first year). We assessed baseline demographics and disease characteristics, survival outcomes, response rates, and safety in pts with MCL who received ibrutinib. Results: Data from 71 evaluable pts with MCL were included in the IA for efficacy (ret n = 56; pro n = 15). Median age at ibrutinib initiation was 72.5 (range 47–88) years, 74.6% of pts were male, and 94.4% had an Eastern Cooperative Oncology Group performance status of 0–1. Median time between diagnosis and ibrutinib initiation was 2.7 years; pts had a median 1 prior line of therapy (range 1–5; 1 line 50.7%, 2 lines 31.0%, ≥3 lines 18.3%). Ibrutinib treatment led to an ORR of 93.0% (complete response 32.4%, partial response 60.6%). Median time to best response was 3.1 months (95% confidence interval [CI], 2.8–4.5) and median duration of response was 25.2 months (95% CI, 16.3‐nonestimable [NE]). With median follow‐up of 24.4 months, median PFS was 22.3 months (95% CI, 18.0–37.9; Figure). PFS rates were 81.3%, 49.5%, 36.8%, and 18.4% at 12, 24, 36, and 48 months, respectively. With median follow‐up of 26.7 months, median overall survival (OS) was 39.4 months (95% CI, 31.8‐NE). The 12‐, 24‐, 36‐, and 48‐month OS rates were 87.3%, 77.0%, 59.8%, and 47.9%, respectively. In the safety analysis (N = 76; ret n = 56; pro n = 20), all pts experienced ≥1 treatment‐emergent adverse event (TEAE), leading to ibrutinib discontinuation in 21.1%. 55.3% of pts had ≥1 serious TEAE. TEAEs of interest (any grade: ret/pro) included infection (51.8%/45.0%), diarrhea (12.5%/25.0%), atrial fibrillation (8.9%/10.0%), rash (7.1%/10.0%), major bleeding (1.8%/10.0%), myalgia (1.8%/10.0%), and hypertension (1.8%/10.0%). 38.2% of pts had received ≥1 antithrombotic therapy. No toxic deaths were reported. Summary/Conclusion: BiRD provides information on RW ibrutinib treatment in routine practice in Belgium, and suggests that ibrutinib is commonly used at first relapse. Compared with clinical trial results, ORR, survival outcomes, and number of TEAEs were similar. Ibrutinib was well tolerated and no new safety signals were reported. As approximately 50% of pts were treated with ibrutinib following 2 or more prior lines of therapy, these median PFS results with ibrutinib are particularly encouraging. image