Ibrutinib for Relapsed / Refractory CLL: A UK and Ireland Analysis of Outcomes in 315 patients

A Jacob, A Bloor, A Whiteway, AE Milne, AA Kirkwood, A Hodson, AS Duncombe, A Schuh, B von Barsewisch, C Fegan, CP Fox, C Pocock, C William, C Dearden, C Hutchinson, C Balotis, C De Lord, DB Kennedy, D Tucker, E VendenbergheE Maughan, E Kumar, F McNichol, F Scott, F Forconi, G Campbell, GA Follows, G Pratt, H Knight, H Parry, I Ringshausen, I Whalley, J Nielson, J Allen, J Arnold, J Gribbon, J Wallis, J Blundell, K Cwynarski, KM Bowles, M Ewings, M Karanth, MJ Dyer, M Hamblin, M Leach, M Badat, N Mir, N Morley, N Bienz, N Philpott, UK CLL Forum

Research output: Contribution to journalArticlepeer-review

99 Citations (Scopus)
4 Downloads (Pure)

Abstract

In 2014, ibrutinib was made available for relapsed/refractory chronic lymphocytic leukaemia (CLL) patients. The UK CLL Forum collected data from UK/Ireland patients with a minimum of 1 year follow-up with pre-planned primary endpoints; the number of patients still on therapy at 1 year (Discontinuation Free Survival; DFS) and 1 year overall survival (OS). With a median 16 months follow-up, data on 315 patients demonstrated 1 year DFS of 73.7% and 1 year OS of 83.8%. Patients with better pre-treatment performance status (PS 0/1 vs 2+) had superior DFS (77.5% vs 61.3%;p<0.0001) and OS (86.3% vs 76.0%;p=0.0001). In univariable analysis OS and DFS were not associated with number of prior lines of therapy or 17p deletion. However, mutivariable analysis identified an interaction between prior lines of therapy, age and 17p deletion suggesting that older patients with 17p deletion did worse when treated with ibrutinib beyond 2nd line. Overall, 55.6% of patients had no first year dose reductions or treatment breaks >14 days and had OS of 89.7%, while 26% of patients had dose reductions and 13% had temporary treatment breaks >14 days. We could not demonstrate a detrimental effect of dose reductions alone (1 year OS: 91.7%), but patients who had first year treatment breaks > 14 days, particularly permanent cessation of ibrutinib had both reduced 1 year OS (68.5%) and also a statistically significant excess mortality rate beyond one year. Although outcomes appear inferior to the RESONATE trial (1 year OS;90%: PFS;84%), this may partly reflect the inclusion of PS 2+ patients and that 17.5% of patients permanently discontinued ibrutinib due to an event other than disease progression.

Original languageEnglish
Pages (from-to)1563-1572
Number of pages10
JournalHaematologica
Volume101
Issue number12
Early online date18 Oct 2016
DOIs
Publication statusPublished - 30 Nov 2016

Keywords

  • Chronic Lymphocytic Leukemia
  • Clinical and Molecular Epidemiology
  • Cytogenetics and Molecular Genetics
  • Lymphocytes
  • ibrutinib

Cite this