Postibrutinib 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 PortellMichael E. Williams, Martin Dreyling, Paul M. Barr, Selina Chen-Kiang, Maurizio DiLiberto, Richard R. Furman, Kristie A. Blum

Research output: Contribution to journalArticlepeer-review

139 Scopus citations


Despite unprecedented clinical activity inmantle cell lymphoma (MCL), primary and acquired resistance to ibrutinib is common. The outcomes and ideal management of patients who experience ibrutinib failure are unclear. We performed a retrospective cohort study of all patients withMCLwho experienced disease progressionwhile receiving ibrutinib across 15 international sites. Medical records were evaluated for clinical characteristics, pathological and radiological data, and therapies used pre- and postibrutinib. A total of 114 subjects met eligibility criteria. The median number of prior therapies was 3 (range, 0-10). The Mantle Cell Lymphoma International Prognostic Index (MIPI) scores at the start of ibrutinib were low, intermediate, and high in 46%, 31%, and 23% of patients, respectively. Of patients with available data prior to ibrutinib and postibrutinib, 34 of 47 and 11 of 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% confidence interval [CI], 1.6-4.9). 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% CI, 3.7-10.4). Multivariate Cox regression analysis of MIPI before postibrutinib 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 after ibrutinib.

Original languageEnglish (US)
Pages (from-to)1559-1563
Number of pages5
Issue number12
StatePublished - Mar 24 2016
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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