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Managing Hematologic Malignancies Is Increasingly Complex

By Edward Li, PharmD, BCOP, Drugs and Biologics Editor

As the pharmacologic management of cancer moves from an era of empiricism towards one where drugs and biologics are “targeted,” the diagnosis, work-up, and evaluation of malignancies have become correspondingly more complicated.   An improved understanding of the pathobiology of hematologic malignancies has allowed clinicians to develop better risk assessment and diagnostic and prognostic criteria through the identification of various biomarkers and other types of analyses.

With these additional criteria, the diagnosis and work-up of hematologic malignancies have become more complex in recent years.  For example, a 2010 update to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines™) for Non-Hodgkin’s Lymphomas incorporated a new treatment algorithm for Adult T-Cell Leukemia/Lymphoma and outlined tests that are essential or useful in certain circumstances to establish a diagnosis and work-up for the patient case.  Furthermore, the NCCN Guidelines™ for Waldenström’s Macroglobulinemia/Lymphoplasmacytic Lymphoma, previously included in the NCCN Guidelines for Multiple Myeloma, are now a separate, revised, and recent addition to the Complete Library of NCCN Guidelines.  This revision contains a new diagnostic section with recommendations for hematopathology review and adequate immunophenotyping to establish diagnosis. An expanded work-up section that includes essential tests along with those that may be useful in certain circumstances is also included.

Increased knowledge of tumor pathobiology has additionally aided in the development of therapies that directly target processes that drive, or are associated with, the malignancy.  Early examples of such target therapies arose in the field of hematologic malignancies.  Rituximab, a monoclonal antibody directed towards the CD20 antigen expressed on various hematologic malignancies, was initially approved by the U.S. Food and Drug Administration (FDA) in 1997 for the management of relapsed or refractory low-grade, B-cell Non-Hodgkin’s Lymphoma.  Imatinib, a tyrosine kinase inhibitor that antagonizes the BCR-ABL fusion protein, was FDA-approved in 2001 for Chronic Myelogenous Leukemia.

FDA-approved targeted therapies in hematalogic malignancies are on the rise. For example, ofatumumab, a monoclonal antibody directed against CD20, was recently FDA-approved for the treatment of refractory Chronic Lymphocytic Leukemia. The epigenetic modulator romidespin, a histone deacetylase inhibitor, also received recent FDA-approval for the treatment of cutaneous T-cell lymphoma.

The majority of newer agents in the pipeline for treating hematologic malignancies are generally not the “traditional” chemotherapy agents.  Instead, they tend to target specific processes and molecules, or they work through other mechanisms (such as modulating genetic expression).  Agents in the pipeline for hematologic malignancies include inhibitors of the mitogen-activated protein kinase pathway (e.g., tipifarnib), the second generation proteosome inhibitor carfilzomib, the immunomodulator pomalidomide, and histone deacetylase inhibitors such as belinostat and panobisnostat.

At the NCCN 5th Annual Congress: Hematologic Malignancies™, many of the issues described above will be discussed.  This congress will feature a wide range of topics, including Multiple Myeloma, Waldenström’s Macroglobulinemia, Chronic Myelogenous Leukemia, and Lymphomas. Supportive care and practice issues in hematologic malignancies will also be discussed.   This meeting will be held on October 8-9, 2010 at the New York Marriot Marquis in New York.  To register for or to find more information about the NCCN 5th Annual Congress, please visit NCCN 5th Annual Congress: Hematologic Malignancies™.