title: Long-term follow-up of MCL patients treated with single-agent ibrutinib: updated safety and efficacy results.
abstract: Ibrutinib, an oral inhibitor of Bruton tyrosine kinase, is approved for patients with mantle cell lymphoma (MCL) who have received one prior therapy. We report the updated safety and efficacy results from the multicenter, open-label phase 2 registration trial of ibrutinib (median 26.7-month follow-up). Patients (N = 111) received oral ibrutinib 560 mg once daily, and those with stable disease or better could enter a long-term extension study. The primary end point was overall response rate (ORR). The median patient age was 68 years (range, 40-84), with a median of 3 prior therapies (range, 1-5). The median treatment duration was 8.3 months; 46% of patients were treated for >12 months, and 22% were treated for ≥2 years. The ORR was 67% (23% complete response), with a median duration of response of 17.5 months. The 24-month progression-free survival and overall survival rates were 31% (95% confidence interval [CI], 22.3-40.4) and 47% (95% CI, 37.1-56.9), respectively. The most common adverse events (AEs) in >30% of patients included diarrhea (54%), fatigue (50%), nausea (33%), and dyspnea (32%). The most frequent grade ≥3 infections included pneumonia (8%), urinary tract infection (4%), and cellulitis (3%). Grade ≥3 bleeding events in ≥2% of patients were hematuria (2%) and subdural hematoma (2%). Common all-grade hematologic AEs were thrombocytopenia (22%), neutropenia (19%), and anemia (18%). The prevalence of infection, diarrhea, and bleeding was highest for the first 6 months of therapy and less thereafter. With longer follow-up, ibrutinib continues to demonstrate durable responses and favorable safety in relapsed/refractory MCL. The trial is registered to www.ClinicalTrials.gov as #NCT01236391.
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX;
authors.forename: Michael L
authors.initials: ML
authors.lastname: Wang
authors.affiliation: Ohio State University Comprehensive Cancer Center, Columbus, OH;
authors.forename: Kristie A
authors.initials: KA
authors.lastname: Blum
authors.affiliation: Weill Cornell Medical College, New York, NY;
authors.forename: Peter
authors.initials: P
authors.lastname: Martin
authors.affiliation: John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ;
authors.forename: Andre
authors.initials: A
authors.lastname: Goy
authors.affiliation: Barts Health National Health Service (NHS) Trust, London, United Kingdom;
authors.forename: Rebecca
authors.initials: R
authors.lastname: Auer
authors.affiliation: University of Wisconsin School of Medicine and Public Health, Madison, WI;
authors.forename: Brad S
authors.initials: BS
authors.lastname: Kahl
authors.affiliation: Jagiellonian University, Krakow, Poland;
authors.forename: Wojciech
authors.initials: W
authors.lastname: Jurczak
authors.affiliation: Stanford University Medical Center, Stanford, CA;
authors.forename: Ranjana H
authors.initials: RH
authors.lastname: Advani
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX;
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Romaguera
authors.affiliation: University of Virginia School of Medicine, Charlottesville, VA;
authors.forename: Michael E
authors.initials: ME
authors.lastname: Williams
authors.affiliation: Hofstra North Shore-Long Island Jewish School of Medicine, Hempstead, NY;
authors.forename: Jacqueline C
authors.initials: JC
authors.lastname: Barrientos
authors.affiliation: Oddzial Kliniczny Onkologii, Centrum Onkologii, Bydgoszcz, Poland;
authors.forename: Ewa
authors.initials: E
authors.lastname: Chmielowska
authors.affiliation: The University of Manchester and the Christie NHS Foundation Trust, Manchester, United Kingdom;
authors.forename: John
authors.initials: J
authors.lastname: Radford
authors.affiliation: Universitatsklinikum Ulm, Klinik fur Innere Medizin II, Ulm, Germany;
authors.forename: Stephan
authors.initials: S
authors.lastname: Stilgenbauer
authors.affiliation: University Hospital LMU Munich, Germany;
authors.forename: Martin
authors.initials: M
authors.lastname: Dreyling
authors.affiliation: Medical University of Warsaw, Warsaw, Poland;
authors.forename: Wieslaw Wiktor
authors.initials: WW
authors.lastname: Jedrzejczak
authors.affiliation: Cancer Research UK Clinical Centre, Southampton General Hospital, Southampton, United Kingdom;
authors.forename: Peter
authors.initials: P
authors.lastname: Johnson
authors.affiliation: Oregon Health and Science University, Portland, OR;
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Spurgeon
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX;
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Pharmacyclics LLC, Sunnyvale, CA; and.
authors.forename: Linda
authors.initials: L
authors.lastname: Baher
authors.affiliation: Pharmacyclics LLC, Sunnyvale, CA; and.
authors.forename: Mei
authors.initials: M
authors.lastname: Cheng
authors.affiliation: Pharmacyclics LLC, Sunnyvale, CA; and.
authors.forename: Dana
authors.initials: D
authors.lastname: Lee
authors.affiliation: Pharmacyclics LLC, Sunnyvale, CA; and.
authors.forename: Darrin M
authors.initials: DM
authors.lastname: Beaupre
authors.affiliation: Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Rule
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D003967:Diarrhea / Q000139:chemically induced / Q000503:physiopathology; D004334:Drug Administration Schedule; D004417:Dyspnea / Q000139:chemically induced / Q000503:physiopathology; D005221:Fatigue / Q000139:chemically induced / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000503:physiopathology; D009503:Neutropenia / Q000139:chemically induced / Q000503:physiopathology; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011505:Protein-Tyrosine Kinases / Q000008:administration & dosage* / Q000009:adverse effects; D012008:Recurrence; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000139:chemically induced / Q000503:physiopathology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase