PF384 EFFECTIVENESS AND SAFETY OF IBRUTINIB FOR CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) IN ROUTINE CLINICAL PRACTICE: INTERIM ANALYSIS (IA) OF THE BELGIAN IBRUTINIB REAL-WORLD DATA (BIRD) STUDY
Authors: A. Janssens, M. André, Z. Berneman, S. Snauwaert, B. De Beleyr, A. Smet, C. Van Bogaert, R. Wapenaar, D. Bron
Journal: HemaSphere (2019)

Background: Single-agent ibrutinib, a first in class, once daily oral inhibitor of Bruton's tyrosine kinase, has shown considerable activity in patients (pts) with CLL in phase 2 trials and improved progression-free survival (PFS) and overall survival (OS) vs chlorambucil in treatment-naïve pts (RESONATE-2™ [NCT01722487]; Burger et al. N Engl J Med. 2015;373:2425–2437) and vs ofatumumab in relapsed/refractory pts (RESONATE™ [NCT01578707]; Byrd et al. N Engl J Med. 2014;371:213–223) in phase 3 registration trials Aims: To assess ibrutinib outcomes in real-world (RW) clinical practice in pts with CLL in Belgium. Methods: BiRD is a multicenter, observational study of pts with a confirmed diagnosis of CLL, mantle cell lymphoma, or Waldenström's macroglobulinemia eligible for ibrutinib reimbursement at treatment initiation (70–80%) or participating in a Medical Need Program and switched to reimbursed treatment (20–30%). Data were collected retrospectively (ret) and prospectively (pro). This IA is based on the CLL population with ≥12 months of treatment follow-up (or who discontinued ibrutinib ≤1 year [yr]). We examined baseline demographics/disease characteristics, survival outcomes, response rates, and safety in pts with CLL receiving ibrutinib. Results: Data from 160 evaluable pts with CLL were included in the IA for efficacy (ret n = 123; pro n = 37). Median age at ibrutinib initiation was 71.3 (range 38.0–90.0) yrs, 62.5% were male, and 85.9% had an Eastern Cooperative Oncology Group performance status of 0–1. Median time from diagnosis to ibrutinib initiation was 6.4 yrs; pts had a median 2 prior lines of therapy (range 0–6; 0 lines 10.0%, 1 line 28.8%, 2 lines 35.0%, ≥3 lines 25.6%). In tested pts, 56/91 (61.5%) had del17p and/or TP53 mutation, and 42/58 (72.4%) had unmutated IGHV. Pts with/without del17p and/or TP53 mutation received ibrutinib in first (28.6%/0%), second (35.7%/28.6%), third (23.2%/34.3%), or fourth/later lines (12.5%/37.2%). Overall response rate was 86.9% (complete response 5.0%, partial response [PR] 52.5%, PR with lymphocytosis 29.4%). Median time to best response was 4.8 months (95% confidence interval [CI], 3.7–5.5) and median duration of response was not reached. With median follow-up of 20.9 months, 26.9% of pts had progressed or died. Median PFS was 38.3 months (95% CI, 34.3-nonestimable [NE]) (Figure); PFS rates at 12, 24, 36, and 48 months were 84.6%, 76.2%, 61.5%, and 44.0%, respectively. Median PFS with ibrutinib was comparable in pts with/without del17p and/or TP53 mutation (38.3 [95% CI, 27.3-NE] vs 37.3 months [95% CI, 25.7-NE]) and with unmutated/mutated IGHV (36.8 [95% CI, 25.7–36.8] vs 37.3 months [95% CI, 37.3–38.3]). With median follow-up of 24.8 months, median OS was not reached; OS rates were 92.5%, 83.8%, and 79.8% at 12, 24, and 36/48 months, respectively. In the safety analysis (N = 189; ret n = 132; pro n = 57), 94.2% of pts had ≥1 treatment-emergent adverse event (TEAE) and 40.2% ≥1 serious TEAE. TEAEs led to dose reduction, interruption, or discontinuation in 38 (20.1%), 49 (25.9%), and 32 (16.9%) pts. TEAEs of interest (any grade: ret/pro) included infection (48.5%/52.6%), diarrhea (8.3%/12.3%), hypertension (3.8%/12.3%) arthralgia (2.3%/12.3%), atrial fibrillation (5.3%/7.0%), myalgia (1.5%/8.8%), and major bleeding (3.8%/5.3%). 26.5% of pts had received antithrombotic therapy.Summary/Conclusion: The BiRD study shows ibrutinib outcomes in an RW population with similar efficacy as clinical trials; most pts did not progress and/or are alive at 4 yrs. TEAEs related to ibrutinib were manageable; no new safety signals were reported.