Tilly Varughese1, Ying Taur1,2, Nina Cohen3, M Lia Palomba2,4, Susan K Seo1,2, Tobias M Hohl1,2, Gil Redelman-Sidi1,2. 1. Infectious Diseases Service, Memorial Sloan Kettering Cancer Center. 2. Department of Medicine, Weill Cornell Medical College. 3. Department of Pharmacy, Memorial Sloan Kettering Cancer Center, New York, New York. 4. Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, New York.
Abstract
Background: Ibrutinib is a Bruton tyrosine kinase inhibitor that is used for the treatment of lymphoid cancers, including chronic lymphocytic leukemia, Waldenström macroglobulinemia, and mantle cell lymphoma. Several case series have described opportunistic infections among ibrutinib recipients, but the full extent of these infections is unknown. We sought to determine the spectrum of serious infections associated with ibrutinib treatment. Methods: We reviewed the electronic medical records of patients with lymphoid cancer at Memorial Sloan Kettering Cancer Center who received ibrutinib during a 5-year period from 1 January 2012 to 31 December 2016. Serious infections were identified by review of the relevant microbiology, clinical laboratory, and radiology data. Risk factors for infection were determined by means of univariate and multivariate analyses. Results: We analyzed findings in 378 patients with lymphoid cancer who received ibrutinib. The most common underlying cancers were chronic lymphocytic leukemia and mantle cell lymphoma. 84% of patients received ibrutinib as monotherapy. Serious infection developed in 43 patients (11.4%), primarily during the first year of ibrutinib treatment. Invasive bacterial infections developed in 23 (53.5%) of these patients, and invasive fungal infections (IFIs) in 16 (37.2%) .The majority of patients with IFIs during ibrutinib therapy (62.5%) lacked classic clinical risk factors for fungal infection (ie, neutropenia, lymphopenia, and receipt of corticosteroids). Infection resulted in death in 6 of the 43 patients (14%). Conclusions: Patients with lymphoid cancer receiving ibrutinib treatment are at risk for serious infections, including IFIs.
Background: Ibrutinib is a Bruton tyrosine kinase inhibitor that is used for the treatment of lymphoid cancers, including chronic lymphocytic leukemia, Waldenström macroglobulinemia, and mantle cell lymphoma. Several case series have described opportunistic infections among ibrutinib recipients, but the full extent of these infections is unknown. We sought to determine the spectrum of serious infections associated with ibrutinib treatment. Methods: We reviewed the electronic medical records of patients with lymphoid cancer at Memorial Sloan Kettering Cancer Center who received ibrutinib during a 5-year period from 1 January 2012 to 31 December 2016. Serious infections were identified by review of the relevant microbiology, clinical laboratory, and radiology data. Risk factors for infection were determined by means of univariate and multivariate analyses. Results: We analyzed findings in 378 patients with lymphoid cancer who received ibrutinib. The most common underlying cancers were chronic lymphocytic leukemia and mantle cell lymphoma. 84% of patients received ibrutinib as monotherapy. Serious infection developed in 43 patients (11.4%), primarily during the first year of ibrutinib treatment. Invasive bacterial infections developed in 23 (53.5%) of these patients, and invasive fungal infections (IFIs) in 16 (37.2%) .The majority of patients with IFIs during ibrutinib therapy (62.5%) lacked classic clinical risk factors for fungal infection (ie, neutropenia, lymphopenia, and receipt of corticosteroids). Infection resulted in death in 6 of the 43 patients (14%). Conclusions: Patients with lymphoid cancer receiving ibrutinib treatment are at risk for serious infections, including IFIs.
Authors: Jan A Burger; Michael J Keating; William G Wierda; Elena Hartmann; Julia Hoellenriegel; Nathalie Y Rosin; Iris de Weerdt; Ghayathri Jeyakumar; Alessandra Ferrajoli; Marylou Cardenas-Turanzas; Susan Lerner; Jeffrey L Jorgensen; Graciela M Nogueras-González; Gracy Zacharian; Xuelin Huang; Hagop Kantarjian; Naveen Garg; Andreas Rosenwald; Susan O'Brien Journal: Lancet Oncol Date: 2014-08-20 Impact factor: 41.316
Authors: Michail S Lionakis; Kieron Dunleavy; Mark Roschewski; Brigitte C Widemann; John A Butman; Roland Schmitz; Yandan Yang; Diane E Cole; Christopher Melani; Christine S Higham; Jigar V Desai; Michele Ceribelli; Lu Chen; Craig J Thomas; Richard F Little; Juan Gea-Banacloche; Sucharita Bhaumik; Maryalice Stetler-Stevenson; Stefania Pittaluga; Elaine S Jaffe; John Heiss; Nicole Lucas; Seth M Steinberg; Louis M Staudt; Wyndham H Wilson Journal: Cancer Cell Date: 2017-05-25 Impact factor: 31.743
Authors: D Vetrie; I Vorechovský; P Sideras; J Holland; A Davies; F Flinter; L Hammarström; C Kinnon; R Levinsky; M Bobrow Journal: Nature Date: 1993-01-21 Impact factor: 49.962
Authors: Ben De Pauw; Thomas J Walsh; J Peter Donnelly; David A Stevens; John E Edwards; Thierry Calandra; Peter G Pappas; Johan Maertens; Olivier Lortholary; Carol A Kauffman; David W Denning; Thomas F Patterson; Georg Maschmeyer; Jacques Bille; William E Dismukes; Raoul Herbrecht; William W Hope; Christopher C Kibbler; Bart Jan Kullberg; Kieren A Marr; Patricia Muñoz; Frank C Odds; John R Perfect; Angela Restrepo; Markus Ruhnke; Brahm H Segal; Jack D Sobel; Tania C Sorrell; Claudio Viscoli; John R Wingard; Theoklis Zaoutis; John E Bennett Journal: Clin Infect Dis Date: 2008-06-15 Impact factor: 9.079
Authors: S Tsukada; D C Saffran; D J Rawlings; O Parolini; R C Allen; I Klisak; R S Sparkes; H Kubagawa; T Mohandas; S Quan Journal: Cell Date: 1993-01-29 Impact factor: 41.582
Authors: Michael L Wang; Simon Rule; Peter Martin; Andre Goy; Rebecca Auer; Brad S Kahl; Wojciech Jurczak; Ranjana H Advani; Jorge E Romaguera; Michael E Williams; Jacqueline C Barrientos; Ewa Chmielowska; John Radford; Stephan Stilgenbauer; Martin Dreyling; Wieslaw Wiktor Jedrzejczak; Peter Johnson; Stephen E Spurgeon; Lei Li; Liang Zhang; Kate Newberry; Zhishuo Ou; Nancy Cheng; Bingliang Fang; Jesse McGreivy; Fong Clow; Joseph J Buggy; Betty Y Chang; Darrin M Beaupre; Lori A Kunkel; Kristie A Blum Journal: N Engl J Med Date: 2013-06-19 Impact factor: 91.245
Authors: John C Byrd; Richard R Furman; Steven E Coutre; Ian W Flinn; Jan A Burger; Kristie A Blum; Barbara Grant; Jeff P Sharman; Morton Coleman; William G Wierda; Jeffrey A Jones; Weiqiang Zhao; Nyla A Heerema; Amy J Johnson; Juthamas Sukbuntherng; Betty Y Chang; Fong Clow; Eric Hedrick; Joseph J Buggy; Danelle F James; Susan O'Brien Journal: N Engl J Med Date: 2013-06-19 Impact factor: 91.245
Authors: Sejal Morjaria; John Frame; Alexandra Franco-Garcia; Alexander Geyer; Mini Kamboj; N Esther Babady Journal: Clin Infect Dis Date: 2019-09-27 Impact factor: 9.079
Authors: Priyanka Banerjee; Ronghua Zhang; Cristina Ivan; Giovanni Galletti; Karen Clise-Dwyer; Federica Barbaglio; Lydia Scarfò; Miguel Aracil; Christian Klein; William Wierda; William Plunkett; Federico Caligaris-Cappio; Varsha Gandhi; Michael J Keating; Maria Teresa S Bertilaccio Journal: Cancer Immunol Res Date: 2019-09-17 Impact factor: 11.151
Authors: Michael J Buege; Anita Kumar; Brianne N Dixon; Laura A Tang; Terry Pak; Jennifer Orozco; Tim J Peterson; Kathryn T Maples Journal: Ann Pharmacother Date: 2020-02-20 Impact factor: 3.154
Authors: Kerry A Rogers; Luay Mousa; Qiuhong Zhao; Seema A Bhat; John C Byrd; Zeinab El Boghdadly; Tomas Guerrero; Lauren B Levine; Fabienne Lucas; Polina Shindiapina; Audrey M Sigmund; Matthew Sullivan; Tracy E Wiczer; Jennifer A Woyach; Farrukh T Awan Journal: Leukemia Date: 2019-05-13 Impact factor: 11.528