Post-ibrutinib outcomes in patients with mantle cell lymphoma

Peter Martin, Kami Maddocks, John P. Leonard, Jia Ruan, Andre Goy, Nina Wagner-Johnston, Simon Rule, Ranjana Advani, David Iberri, Tycel Phillips, Stephen Spurgeon, Eliana Kozin, Katherine Noto, Zhengming Chen, Wojciech Jurczak, Rebecca Auer, Ewa Chmielowska, Stephan Stilgenbauer, Johannes Bloehdorn, Craig Portell, Michael E. Williams, Martin Dreyling, Paul M. Barr, Selina Chen-Kiang, Maurizio DiLiberto, Richard R. Furman and Kristie A. Blum

Key points

  • Patients with mantle cell lymphoma that progressed during treatment with ibrutinib have a poor outcome.

  • There are no therapies that appear to be uniquely successful in the post-ibrutinib setting. The post-ibrutinib setting is an unmet need.


Despite unprecedented clinical activity in mantle cell lymphoma (MCL), primary and acquired resistance to ibrutinib is common. The outcomes and ideal management of patients that experience ibrutinib failure are unclear. We performed a retrospective cohort study of all patients with MCL that experienced disease progression while receiving ibrutinib across 15 international sites. Medical records were evaluated for clinical characteristics, pathological, and radiological data, and therapies used pre and post ibrutinib. A total of 114 subjects met eligibility criteria. The median number of prior therapies was 3 (range 0-10). The MIPI scores at start of ibrutinib were low, intermediate, and high in 46%, 31%, and 23%, respectively. Of patients with available data prior to ibrutinib and post-ibrutinib, 34/47 and 11/12 had a Ki67>30%. The median time on ibrutinib was 4.7 months (range 0.7-43.6). The median overall survival (OS) following cessation of ibrutinib was 2.9 months (95% CI 1.6-4.9 months). Of the 104 patients with data available, 73 underwent subsequent treatment an average of 0.3 months after stopping ibrutinib with a median OS of 5.8 months (95% C.I. 3.7 to 10.4 months). Multivariate Cox regression analysis of MIPI prior to post-ibrutinib treatment, and subsequent treatment with bendamustine, cytarabine, or lenalidomide failed to reveal any association with OS. Poor clinical outcomes were noted in the majority of patients with primary or secondary ibrutinib resistance. We could not identify treatments that clearly improved outcomes. Future trials should focus on understanding the mechanisms of ibrutinib resistance and on treatment following ibrutinib.

  • Submitted October 1, 2015.
  • Accepted December 6, 2015.