ASH News Daily 2012 - Sunday, December 9, 2012 - (Page A-2)

Page A–2 ® ASH News Daily 2012 Editorial Board Editor Michael R. Bishop, MD University of Chicago Authors Jose A. Bufill, MD Michiana Hematology Oncology, PC Jenna D. Goldberg, MD Memorial SloanKettering Cancer Center Matthew Hsieh, MD National Institutes of Health Marc Kahn, MD, MBA Tulane University School of Medicine Andrew D. Leavitt, MD University of California, San Francisco The information contained in ASH News Daily is provided solely for educational purposes. A diversity of opinions exists in the field of hematology, and the articles in this publication are often intended to inform readers about more than one point of view. These articles are not comprehensive and should not be used as a substitute for traditional sources of hematology information, traditional diagnostic and treatment information, or the individual judgment of health-care providers. The views expressed in ASH News Daily do not necessarily represent ASH’s views, and their inclusion in this publication should not be interpreted as an endorsement by ASH. ASH is not responsible for any inaccurate or inappropriate use of the information, publications, products, or services discussed or advertised within. ©2012 by the American Society of Hematology All materials contained in this newspaper are protected by copyright laws and may not be used, reproduced, or otherwise exploited in any manner without the express prior permission of ASH News Daily. Contributing authors have declared any financial interest in a product or in potentially competing products, regardless of the dollar amount. Any such financial interest is noted with the author byline. LYMPHOMA Chronic Lymphocytic Leukemia: New Insights, New Challenges BY JOSE A. BUFILL, MD quarely at the center of the process of malignant transformation in chronic lymphocytic leukemia (CLL) is the B-cell receptor and the molecular pathways dependent upon it. New agents targeting these pathways have improved and prolonged the lives of end-stage patients, an observation that has generated both great expectations and a new set of clinical challenges. These challenges will be addressed in an Education Program session, “Chronic Lymphocytic Leukemia: Can New Prognostic Factors Guide New Therapeutic S Approaches?” scheduled this morning at 7:30 in Hall 5, Level 1, Building B (GWCC). Understanding the difference between normal and pathologic B-cell activation is the key to understanding CLL. In the normal state, B cells are in constant dialogue with their microenvironment, acknowledging the presence of chemical neighbors as either friends (immune tolerance) or foes (immune response). When a threat is detected, the B-cell receptor is activated, setting off a series of reactions that ultimately lead to the generation of antigen-specific antibodies. The process of antibody generation – called somatic hypermutation – involves a frenzy of shuffling and reshuffling of antibodyproducing genes, whose products determine the chemical properties of the tip of the antibody – the variable region of the immunoglobulin heavy chain (IgHV) – enabling the antibody to bind and neutralize its corresponding antigen with razorsharp precision. In the malignant B cells of CLL, the presence or absence of hypermutation is the most reliable determinant of prognosis. Unmutated CLL cells are a less mature B cell whose clinical course is more aggressive and whose prognosis is much worse. Mutated CLL cells are more mature; their clinical course is usually indolent. The important role of IgHV and other newer prognostic markers will be reviewed in detail by Nicholas Chiorazzi, MD, of The Feinstein Institute for Medical Research, North Shore-LIJ Health System. Dr. Chiorazzi is also the chair of this session. Steps in the molecular pathways activated by the B-cell receptor have emerged as effective therapeutic targets in CLL (figure). Adrian Wiestner, MD, PhD, of the National Institutes of Health in Bethesda will review a few of the new drugs that have en- Figure A: Chemical Structures of Signal Kinase Inhibitors ASH NEWS DAILY Sunday, December 9, 2012 Figure B: Kinase Inhibitors and the B-Cell Receptor Pathway Woyach JA, Johnson AJ, Byrd JC. The B-cell receptor signaling pathway as a therapeutic target in CLL. Blood. 2012;120:1175-1184. tered clinical trials. One of these is ibrutinib (PCI 32765), an agent that optimists have dubbed “the imatinib of CLL” after dramatic and durable responses were observed in patients with end-stage disease. The exciting, updated results of a multi-center phase Ib/II study of ibrutinib in patients with untreated, relapsed, or refractory disease (abstract 189) will be presented by John C. Byrd, MD, of The Ohio State University today at 5:00 p.m. in the Thomas Murphy Ballroom 4, Level 5, Building B. Among the many striking biologic observations described with ibrutinib is the development of “redistribution lymphocytosis,” a rapid shift in lymphocytes from nodes and spleen into peripheral blood. When it occurs, the lymphocyte doubling time may be measured in weeks and may take weeks to resolve. It is an expression of benefit rather than progression, and investigators have emphasized that response criteria should be re- vised to take this phenomenon into account. The push to redefine response criteria in CLL has also been prompted by higher complete response rates seen with more effective therapy. Paolo Ghia, MD, PhD, from the Università Vita-Salute San Raffaele, Milano, Italy, will highlight promising new measures of response and survival in patients with CLL. The concept of minimal residual disease (MRD), as defined by PCR- or flow cytometry-based techniques, may be a reliable and independent predictor of outcomes when used in patients after completion of therapy. Dr. Ghia will enthusiastically argue for the use of MRD as a marker of survival and of therapeutic efficacy. Taken together, these talks suggest that the long-term control – if not the “cure” – of symptomatic CLL may be a realistic expectation in the near future. Dr. Bufill indicated no relevant conflicts of interest.

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ASH News Daily 2012 - Sunday, December 9, 2012

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