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Blood. 2016 Mar 24;127(12):1559-63. doi: 10.1182/blood-2015-10-673145. Epub 2016 Jan 13.

Postibrutinib outcomes in patients with mantle cell lymphoma.

Author information

1
Department of Medicine, Weill Cornell Medical College, New York, NY;
2
Ohio State University Comprehensive Cancer Center, Columbus, OH;
3
Hackensack University Medical Center, Hackensack, NJ;
4
Division of Oncology, Washington University School of Medicine, St. Louis, MO;
5
Department of Haematology, Plymouth University Peninsula Schools of Medicine and Dentistry and Derriford Hospital, Plymouth, United Kingdom;
6
Stanford Cancer Institute, Stanford, CA;
7
Department of Internal Medicine, University of Michigan, Ann Arbor, MI;
8
Center for Hematologic Malignancies, Oregon Health and Science University, Portland, OR;
9
Department of Healthcare Policy and Research, Weill Cornell Medical College, New York, NY;
10
Department of Hematology, Jagiellonian University, Krakow, Poland;
11
St. Bartholomew's Hospital, London, United Kingdom;
12
Oddzial Kliniczny Onkologii, Bydgoszcz, Poland;
13
Universitätsklinikum Ulm, Ulm, Germany;
14
University of Virginia Cancer Center, Charlottesville, VA;
15
Klinikum der Universität München, Munich, Germany;
16
Department of Medicine, University of Rochester Medical Center, Rochester, NY; and.
17
Department of Pathology, Weill Cornell Medical College, New York, NY.

Abstract

Despite unprecedented clinical activity in mantle 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 with MCL who 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 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.

Comment in

PMID:
26764355
DOI:
10.1182/blood-2015-10-673145
[Indexed for MEDLINE]
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