Long term safety and efficacy results of ibrutinib use in CLL patients

On 8 February 2018, long term safety and efficacy study results of ibrutinib use in patients with chronic lymphocytic leukemia (CLL) were published online in Blood. The study by Susan O’Brien, University of Texas MD Anderson Cancer Center, and the University of California, and colleagues, highlighted outcomes in relapsed/refractory (R/R) and treatment-naïve (TN) patients after a follow-up of 5 years.

Study Overview
  • N = 132 patients included in the study, either TN (n = 31) or R/R (n = 101)
  • Treatment dose was 420 or 840mg ibrutinib orally once daily
  • The primary endpoint of the study was safety and secondary endpoints included overall response rate (ORR), complete response (CR), progression-free survival (PFS) and overall survival (OS)
  • Median time on treatment; TN = 65 months and R/R = 39 months
  • Discontinuation of treatment occurred in 72% of R/R patients (disease progression 33% and adverse events (AEs) 21%) and 45% of TN patients (disease progression 6% and AEs 19%)
  • Most common ≥3 AEs for TN vs R/R = hypertension (32% vs 25%), pneumonia (10% vs 27%), neutropenia (3% vs 21%), thrombocytopenia (3% vs 11%) and atrial fibrillation (6% vs 9%)
  • Analysis showed that R/R patients with unmutated IGHV and CK were more likely to discontinue treatment. Additionally, discontinuation rates were not affected by del(11q)
  • Median time on study = 61.5 months (0.7–75.2)
  • Efficacy results described as TN vs R/R:
    • Median PFS = not reached (NR) vs 51 months
    • 5-year estimated PFS = 92% vs 44%
    • Median OS = NR vs NR
    • 5-year OS = 92% vs 60%
    • Median duration of response (DOR) = 72.8 months vs 57
    • ORR = 87% (95% CI, 70.2–96.4%) vs 89% (95% CI, 81.3–94.4%)
    • CR = 29% vs 10%
    • Disease progression at 5-year follow-up = 3% vs 36%
  • Patients with del(11q) and CK had a shorter DOR. The authors also found that patients with del(17p) and CK had shorter median PFS and OS. In further analysis, it was also found that patients with CK and del(17p) had lower ORR, DOR, median PFS and OS compared to those with just CK
  • Patients with fewer lines of therapy (1–3) experienced better ORR and median DOR

The authors concluded that ibrutinib as a single agent showed long term efficacy and durable responses with an acceptable safety profile in patients with CLL. Similar results were also reflected in another long term follow-up study with ibrutinib in CLL patients by Inhye Ahn et al. The study authors found that ibrutinib also demonstrated durable responses after 5 years in TN and R/R CLL patients.

  1. O’Brien S. et al. Single-agent ibrutinib in treatment-naïve and relapsed/refractory chronic lymphocytic leukemia: a 5-year experience. Blood. 2018 Feb 2. pii: blood-2017-10-810044. doi: 10.1182/blood-2017-10-810044. [Epub ahead of print]
  2. Ahn IE. Et al. Depth and durability of response to ibrutinib in CLL: 5-year follow-up of a phase II study. Blood. 2018 Feb 26. pii: blood-2017-12-820910. doi: 10.1182/blood-2017-12-820910. [Epub ahead of print]
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