TY - JOUR
T1 - Chronic lymphocytic leukemia
T2 - New concepts for future therapy
AU - Wierda, William
AU - Chiorazzi, Nicholas
AU - Dearden, Claire
AU - Brown, Jennifer
AU - Montserrat, Emili
AU - Shpall, Elizabeth
AU - Stilgenbauer, Stephan
AU - Muneer, Sabeeha
AU - Grever, Michael
N1 - Funding Information:
William G. Wierda has served as a consultant or been on an advisory board for Berlex Oncology/Bayer Pharmaceuticals Corporation, Biogen Idec, Celgene Corporation, Cephalon, Inc., Genentech, Inc., Genzyme Corporation, Ligand Pharmaceuticals, Inc., MedImmune, Inc., Micromet, Inc., and Schering-Plough Corporation; has served on a Speaker's Bureau for Celgene Corporation, Cephalon, Inc., Genzyme Corporation, GlaxoSmithKline, and Roche Pharmaceuticals; and has received research funding from Abbott Laboratories, Berlex Oncology/Bayer Pharmaceuticals Corporation, Genmab, GlaxoSmithKline, Memgen, LLC, sanofi-aventis, U.S., and Sunesis Pharmaceuticals, Inc. Emili Montserrat has received research funding from GlaxoSmithKline and Roche Pharmaceuticals, and has served as a consultant or been on an advisory/research panel for Roche Pharmaceuticals. Claire Dearden has served as a consultant or been on an advisory/research panel for Genzyme Corporation, GlaxoSmithKline, and Roche Pharmaceuticals. Jennifer R. Brown has received research funding from Celgene Corporation and Genzyme Corporation, and has served as a consultant or been on an advisory/research panel for Calistoga Pharmaceuticals, Inc. and Celgene Corporation. Stephan Stilgenbauer has received research funding from Amgen, Bayer Healthcare AG, Celgene Corporation, Genzyme Corporation, GlaxoSmithKline, Mundipharma Laboratories GmbH, Roche Pharmaceuticals, and sanofi-aventis. The remaining authors have no relevant relationships to disclose.
PY - 2010/10
Y1 - 2010/10
N2 - Over the past several years, we have witnessed rapid advances in our understanding of the biology and treatment of chronic lymphocytic leukemia (CLL). New prognostic factors have been characterized that help identify patients at high risk of rapid disease progression, refractoriness to treatment, and short overall survival (OS). These advances have led to a significant paradigm shift in the management of CLL. Novel therapeutic strategies, including combinations of monoclonal antibodies with conventional chemotherapy, have dramatically improved response rates, remission duration, and recently, OS. However, these benefits do not appear to extend to certain patient subsets, especially those with unfavorable clinical or cytogenetic risk factors. The majority of patients with CLL will invariably relapse following first-line therapy and can acquire high-risk genetic abnormalities. Repeated treatment leads to eventual therapeutic refractoriness and shortened survival compared with age-matched healthy individuals. Several novel agents and strategies, including next-generation anti-CD20 monoclonal antibodies, the alkylating agent bendamustine, the immunomodulatory agent lenalidomide, the cyclin-dependent kinase inhibitor flavopiridol, and small-molecule Bcl2 inhibitors, are currently under clinical investigation as novel agents that will hopefully improve treatment outcomes for CLL. Though allogeneic stem cell transplantation offers curative potential, it also presents clinical challenges in terms of patient appropriateness, donor availability, and timing. The merits and challenges of incorporating these treatment modalities into the treatment algorithm for patients with CLL, as discussed by a panel of experts in CLL, are outlined in this article.
AB - Over the past several years, we have witnessed rapid advances in our understanding of the biology and treatment of chronic lymphocytic leukemia (CLL). New prognostic factors have been characterized that help identify patients at high risk of rapid disease progression, refractoriness to treatment, and short overall survival (OS). These advances have led to a significant paradigm shift in the management of CLL. Novel therapeutic strategies, including combinations of monoclonal antibodies with conventional chemotherapy, have dramatically improved response rates, remission duration, and recently, OS. However, these benefits do not appear to extend to certain patient subsets, especially those with unfavorable clinical or cytogenetic risk factors. The majority of patients with CLL will invariably relapse following first-line therapy and can acquire high-risk genetic abnormalities. Repeated treatment leads to eventual therapeutic refractoriness and shortened survival compared with age-matched healthy individuals. Several novel agents and strategies, including next-generation anti-CD20 monoclonal antibodies, the alkylating agent bendamustine, the immunomodulatory agent lenalidomide, the cyclin-dependent kinase inhibitor flavopiridol, and small-molecule Bcl2 inhibitors, are currently under clinical investigation as novel agents that will hopefully improve treatment outcomes for CLL. Though allogeneic stem cell transplantation offers curative potential, it also presents clinical challenges in terms of patient appropriateness, donor availability, and timing. The merits and challenges of incorporating these treatment modalities into the treatment algorithm for patients with CLL, as discussed by a panel of experts in CLL, are outlined in this article.
KW - Alemtuzumab
KW - Bendamustine
KW - Flavopiridol
KW - Lenalidomide
KW - Ofatumumab
UR - http://www.scopus.com/inward/record.url?scp=79952277727&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79952277727&partnerID=8YFLogxK
U2 - 10.3816/CLML.2010.n.070
DO - 10.3816/CLML.2010.n.070
M3 - Review article
C2 - 21030350
AN - SCOPUS:79952277727
SN - 2152-2650
VL - 10
SP - 369
EP - 378
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
IS - 5
ER -