Single-Agent Ibrutinib in Treatment-Naïve and Relapsed/Refractory Chronic Lymphocytic Leukemia: A 5-Year Experience

Susan O'Brien, Richard R. Furman, Steven Coutre, Ian W. Flinn, Jan A. Burger, Kristie Blum, Jeff Sharman, William Wierda, Jeffrey Jones, Weiqiang Zhao, Nyla A. Heerema, Amy J. Johnson, Ying Luan, Danelle F. James, Alvina D. Chu and John C. Byrd

Key points

  • This 5-year experience demonstrates sustained single-agent efficacy of ibrutinib in patients with CLL, with CR rates increasing over time.

  • Long-term ibrutinib was well tolerated with no new safety signals, and rates of grade ≥3 cytopenias decreased with continued therapy.


We previously reported durable responses and manageable safety of ibrutinib from a 3-year follow-up of treatment-naive (TN) older patients (≥65 years) and relapsed/refractory (R/R) patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). We now report on long-term efficacy and safety with median follow-up of 5 years in this patient population with TN (N=31) and R/R (N=101) CLL/SLL. With the current 5-year follow-up, ibrutinib continues to yield a high overall response rate of 89%, with complete response rates increasing over time to 29% in TN and 10% in R/R patients. The median progression-free survival (PFS) was not reached in TN patients. The 5-year PFS rate was 92% in TN and 44% in R/R patients. Median PFS in R/R patients was 51 months and in those with del(11q), del(17p), and unmutated IGHV was 51, 26, and 43 months, respectively, demonstrating long-term efficacy of ibrutinib in some high-risk subgroups. Survival outcomes were less robust for R/R patients with del(17p) and those who received more prior therapies. The onset of grade ≥3 cytopenias, such as neutropenia, and thrombocytopenia, decreased over time. Treatment–limiting adverse events were more frequent during the first year compared with subsequent time periods. These results demonstrate sustained efficacy and acceptable tolerability of ibrutinib over extended time, providing the longest experience for Bruton’s tyrosine kinase inhibitor treatment in patients with CLL/SLL. The trials were registered at as NCT01105247 and NCT01109069.

  • Submitted October 13, 2017.
  • Accepted January 24, 2018.