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Ibrutinib, Obinutuzumab, Idelalisib, and Beyond: Review of Novel and Evolving Therapies for Chronic Lymphocytic Leukemia
Author(s) -
Chung Clement,
Lee Rosetta
Publication year - 2014
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/phar.1509
Subject(s) - ibrutinib , idelalisib , obinutuzumab , chronic lymphocytic leukemia , medicine , rituximab , oncology , venetoclax , leukemia , immunology , lymphoma
Chronic lymphocytic leukemia ( CLL ) is a neoplasm resulting from the progressive accumulation of functionally incompetent monoclonal B lymphocytes in the blood, bone marrow, lymph nodes, and spleen. It is the most common leukemia in Western countries and typically occurs in elderly patients. Initial treatment of CLL often includes a first‐generation anti‐ CD 20 antibody (rituximab) with chemotherapy and is the current standard of treatment for “younger” old adults (< 70 yrs of age) or older, clinically fit patients. However, because disease progression and drug resistance are inevitable, patients typically die from their disease or treatment‐related complications. Improved understanding of the B‐cell receptor signaling pathway, which is essential for normal B‐cell growth and tumorigenesis, has led to the development of targeted therapies, with improved short‐term clinical outcomes. Ibrutinib, obinutuzumab, and idelalisib, three novel agents recently approved by the U.S. Food and Administration for CLL , all have the potential to change the treatment paradigm. In this article, we describe the pathogenesis of CLL and some of its prognostic factors. Emphasis is on the pharmacology, dosing, clinical efficacy, safety, and place of therapy of ibrutinib, obinutuzumab, and idelalisib. Investigational agents that target different parts of the CLL pathogenic pathway are also described.