Bortezomib in the rapid reduction of high sustained antibody titers in disorders treated with therapeutic protein: lessons learned from Pompe disease
| Autor: | Amy S. Rosenberg, Judeth K. McGann, Jonathan D. Feldman, David Viskochil, Priya S. Kishnani, Robert L. Conway, Jesse A. Tannenbaum, Sean N. Prater, Joyce A. Kobori, Suhrad G. Banugaria, Carrie Bailey, Renuka Gera |
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| Rok vydání: | 2012 |
| Předmět: |
Male
education Plasma Cells Antineoplastic Agents Disease Antibodies Article Bortezomib Pharmacotherapy immune system diseases hemic and lymphatic diseases Glycogen storage disease type II medicine Humans Child Genetics (clinical) biology business.industry Glycogen Storage Disease Type II Antibody titer Immunoglobulins Intravenous Enzyme replacement therapy medicine.disease Boronic Acids Methotrexate Treatment Outcome Child Preschool Pyrazines Immunology biology.protein Drug Therapy Combination Antibody business medicine.drug |
| Zdroj: | Genetics in medicine : official journal of the American College of Medical Genetics. 15(2) |
| ISSN: | 1530-0366 |
| Popis: | High sustained antibody titers complicate many disorders treated with a therapeutic protein, including those treated with enzyme replacement therapy, such as Pompe disease. Although enzyme replacement therapy with alglucosidase alfa (Myozyme) in Pompe disease has improved the prognosis of this otherwise lethal disorder, patients who develop high sustained antibody titers to alglucosidase alfa enter a prolonged phase of clinical decline resulting in death despite continued enzyme replacement therapy. Clinically effective immune-tolerance induction strategies have yet to be described in the setting of an entrenched immune response characterized by high sustained antibody titers, wherein antibody-producing plasma cells play an especially prominent role.We treated three patients with infantile Pompe disease experiencing marked clinical decline due to high sustained antibody titers. To target the plasma cell source of high sustained antibody titers, a regimen based on bortezomib (Velcade) was used in combination with rituximab, methotrexate, and intravenous immunoglobulin.The treatment regimen was well tolerated, with no obvious side effects. Patient 1 had a 2,048-fold, and patients 2 and 3 each had a 64-fold, reduction in anti-alglucosidase alfa antibody titer, with concomitant sustained clinical improvement.The addition of bortezomib to immunomodulatory regimens is an effective and safe treatment strategy in infantile Pompe disease, with potentially broader clinical implications. |
| Databáze: | OpenAIRE |
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