Ibrutinib, a Bruton’s tyrosine kinase inhibitor used for treatment of lymphoproliferative disorders, eliminates both aeroallergen skin test and basophil activation test reactivity

• Published in: Journal of allergy and clinical immunology 2017-09, Vol.140 (3), p.875-879.e1
• Main Authors: Regan, Jennifer A., Cao, Yun, Dispenza, Melanie C., Ma, Shuo, Gordon, Leo I., Petrich, Adam M., Bochner, Bruce S.
• Format: Article
• Language: English
• Subjects: Agammaglobulinaemia Tyrosine Kinase - antagonists & inhibitors; Aged; Allergens - immunology; Anaphylaxis; Anti-Allergic Agents - therapeutic use; Asthma; Basophils - drug effects; Basophils - immunology; Drug dosages; Food allergies; Humans; Immunoproliferative diseases; Leukemia; Lymphocytes; Lymphoma; Lymphoproliferative Disorders - drug therapy; Lymphoproliferative Disorders - immunology; Male; Middle Aged; Protein Kinase Inhibitors - therapeutic use; Pyrazoles - therapeutic use; Pyrimidines - therapeutic use; Skin Tests; Studies; Tyrosine kinase inhibitors
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2017.03.013

Tyrosine kinases, including Bruton's tyrosine kinase (BTK), have been shown to be critical for allergen reactivity by transducing Fc[epsilon]RI crosslinking signals into cellular activation and mediator release from mast cells and basophils.2 Pharmacyclics, Inc, together with Janssen Pharmaceuticals, recently received Food and Drug Administration approval of ibrutinib (Imbruvica, PCI-32765) as a selective, irreversible BTK inhibitor for the treatment of mantle cell lymphoma, chronic lymphocytic leukemia (CLL), and Waldenstrom's macroglobulinemia. Furthermore, multiple studies have shown defects in Fc[epsilon]RI-dependent mast cell degranulation and cytokine production in patients with X-linked agammaglobulinemia, a disease caused by BTK deficiency, or in BTK null mice.2,8 These data suggest that BTK signaling plays a critical role in basophil and mast cell IgE-dependent activation, and therefore, its safe and effective pharmacologic inhibition could result in profound antiallergic effects. Using a Northwestern University institutional review board (IRB)-approved protocol, we screened a total of 28 out of 35 patients before the start of commercial ibrutinib treatment for treatment of mantle cell lymphoma, CLL, or Waldenstrom's macroglobulinemia over a period of approximately 18 months for the presence of aeroallergen sensitivity by brief questionnaire (see this article's Online Repository at www.jacionline.org), BAT, and aeroallergen skin testing using the Multi-Test II device (Lincoln Diagnostics, Inc, Decatur, Ill) using 8 skin test materials (saline, histamine, cat allergen, dust mite mix, ragweed mix, mold mix, tree mix, and grass mix from ALK-Abello, Round Rock, Tex). 1 R.S. Gupta, E.E. Springston, M.R. Warrier, B. Smith, R. Kumar, J. Pongracic, The prevalence, severity, and distribution of childhood food allergy in the United States, Pediatrics, Vol. 128, 2011, 9-17 2 D. Hata, Y. Kawakami, N. Inagaki, C.S. Lantz, T. Kitamura, W.N. Khan, J Exp Med, Vol. 187, 1998, 1235-1247 3 J.C. Byrd, R.R. Furman, S.E. Coutre, I.W. Flinn, J.A. Burger, K.A. Blum, Targeting Btk with ibrutinib in relapsed chronic lymphocytic leukemia, N Engl J Med, Vol. 369, 2013, 32-42 4 M.L. Wang, S. Rule, P. Martin, A. Goy, R. Auer, B.S. Kahl, Targeting Btk with ibrutinib in relapsed or refractory mantle-cell lymphoma, N Engl J Med, Vol. 369, 2013, 507-516 5 S.P. Treon, C.K. Tripsas, K. Meid, D. Warren, G. Varma, R. Green, N Engl J Med, Vol. 372, 2015, 1430-1440 6 R.B. Advanti, J.J.