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Three-year follow-up of treatment-naïve and previously treated patients with CLL and SLL receiving single-agent ibrutinib

John C. Byrd, Richard R. Furman, Steven E. Coutre, Jan A. Burger, Kristie A. Blum, Morton Coleman, William G. Wierda, Jeffrey A. Jones, Weiqiang Zhao, Nyla A. Heerema, Amy J. Johnson, Yun Shaw, Elizabeth Bilotti, Cathy Zhou, Danelle F. James and Susan O'Brien

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  • Atypical Infectious Complications as Adverse Events Due to Ibrutinib
    • Natalie Goldstein, Medical Student Tufts University School of Medicine
    • Other Contributors:
      • Athena Kritharis, Hematology/Oncology Fellow
      • Michael Coyle, Hematology/Oncology Fellow
      • Mabi Singh, Associate Professor
      • Kenneth Miller, Hematology/Oncology Professor of Medicine
      • Andrew Evens, Hematology/Oncology Professor of Medicine

    Studies of ibrutnib have shown an overall favorable therapeutic index, but the relatively short timeframe and limited number of patients in clinical trials treated to date restrict insights into less common and potential serious toxicities. We report two, severe atypical infections in CLL/SLL patients treated with ibruitinib.

    Case 1: A 64-year-old man with relapsed/refractory CLL/SLL presented with severe, painful oral ulcers 4 months after starting ibruitinib. After being observed initially for four years, he was treated with pentostatin/cyclophosphamide/rituximab (6 cycles) followed by lenalidomide maintenance (9 months) with 3-year remission. The lesions did not improve with antiviral therapy, steroids or antibiotics (Figure) and the cultures demonstrated enterovirus infection. The lesions ultimately improved with intravenous immunoglobulin.

    Case 2: An 89-year-old Vietnamese woman with history of latent Mycobacterium tuberculosis (MTB) (diagnosed/treated in 1990) and untreated CLL/SLL with 17p deletion (Figure) presented with severe, acute-onset hemoptysis. Three weeks prior, she started ibrutinib for bulky lymphadenopathy. She had no pulmonary symptoms prior to ibrutinib. Chest-computed tomography revealed prominent bilateral pulmonary opacities and sputum stains were positive for acid-fast bacilli (AFB) and the smear/culture was positive for non-MTB AFB (Figure).

    The pathogenesis of these ibrutinib-related atypical infections are not known, althou...

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    Conflict of Interest:
    None declared.