title: Postibrutinib outcomes in patients with mantle cell lymphoma.
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.
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, NY;
authors.forename: Peter
authors.initials: P
authors.lastname: Martin
authors.affiliation: Ohio State University Comprehensive Cancer Center, Columbus, OH;
authors.forename: Kami
authors.initials: K
authors.lastname: Maddocks
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, NY;
authors.forename: John P
authors.initials: JP
authors.lastname: Leonard
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, NY;
authors.forename: Jia
authors.initials: J
authors.lastname: Ruan
authors.affiliation: Hackensack University Medical Center, Hackensack, NJ;
authors.forename: Andre
authors.initials: A
authors.lastname: Goy
authors.affiliation: Division of Oncology, Washington University School of Medicine, St. Louis, MO;
authors.forename: Nina
authors.initials: N
authors.lastname: Wagner-Johnston
authors.affiliation: Department of Haematology, Plymouth University Peninsula Schools of Medicine and Dentistry and Derriford Hospital, Plymouth, United Kingdom;
authors.forename: Simon
authors.initials: S
authors.lastname: Rule
authors.affiliation: Stanford Cancer Institute, Stanford, CA;
authors.forename: Ranjana
authors.initials: R
authors.lastname: Advani
authors.affiliation: Stanford Cancer Institute, Stanford, CA;
authors.forename: David
authors.initials: D
authors.lastname: Iberri
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, MI;
authors.forename: Tycel
authors.initials: T
authors.lastname: Phillips
authors.affiliation: Center for Hematologic Malignancies, Oregon Health and Science University, Portland, OR;
authors.forename: Stephen
authors.initials: S
authors.lastname: Spurgeon
authors.affiliation: Center for Hematologic Malignancies, Oregon Health and Science University, Portland, OR;
authors.forename: Eliana
authors.initials: E
authors.lastname: Kozin
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, NY;
authors.forename: Katherine
authors.initials: K
authors.lastname: Noto
authors.affiliation: Department of Healthcare Policy and Research, Weill Cornell Medical College, New York, NY;
authors.forename: Zhengming
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Hematology, Jagiellonian University, Krakow, Poland;
authors.forename: Wojciech
authors.initials: W
authors.lastname: Jurczak
authors.affiliation: St. Bartholomew's Hospital, London, United Kingdom;
authors.forename: Rebecca
authors.initials: R
authors.lastname: Auer
authors.affiliation: Oddzial Kliniczny Onkologii, Bydgoszcz, Poland;
authors.forename: Ewa
authors.initials: E
authors.lastname: Chmielowska
authors.affiliation: Universitätsklinikum Ulm, Ulm, Germany;
authors.forename: Stephan
authors.initials: S
authors.lastname: Stilgenbauer
authors.affiliation: Universitätsklinikum Ulm, Ulm, Germany;
authors.forename: Johannes
authors.initials: J
authors.lastname: Bloehdorn
authors.affiliation: University of Virginia Cancer Center, Charlottesville, VA;
authors.forename: Craig
authors.initials: C
authors.lastname: Portell
authors.affiliation: University of Virginia Cancer Center, Charlottesville, VA;
authors.forename: Michael E
authors.initials: ME
authors.lastname: Williams
authors.affiliation: Klinikum der Universität München, Munich, Germany;
authors.forename: Martin
authors.initials: M
authors.lastname: Dreyling
authors.affiliation: Department of Medicine, University of Rochester Medical Center, Rochester, NY; and.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Barr
authors.affiliation: Department of Pathology, Weill Cornell Medical College, New York, NY.
authors.forename: Selina
authors.initials: S
authors.lastname: Chen-Kiang
authors.affiliation: Department of Pathology, Weill Cornell Medical College, New York, NY.
authors.forename: Maurizio
authors.initials: M
authors.lastname: DiLiberto
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, NY;
authors.forename: Richard R
authors.initials: RR
authors.lastname: Furman
authors.affiliation: Ohio State University Comprehensive Cancer Center, Columbus, OH;
authors.forename: Kristie A
authors.initials: KA
authors.lastname: Blum
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D005260:Female; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010880:Piperidines; D016016:Proportional Hazards Models; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011720:Pyrazoles / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D010880:Piperidines; D011720:Pyrazoles; D011743:Pyrimidines; C551803:ibrutinib; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000225:Adenine