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Beyond RCHOP: A Blueprint for Diffuse Large B Cell Lymphoma Research
Grzegorz S Nowakowski1, Kristie A Blum2, Brad S Kahl2
1Department of Medicine, Mayo Clinic, Rochester, MN (GSN); Department of Internal Medicine, Ohio State University, Columbus, OH (KAB); Department of Medicine, Oncology Division, Washington University, St. Louis, MO (BSK); Wilmot Cancer Center and Division of Hematology/Oncology, University of Rochester, Rochester, NY (JWF); Coordinating Center for Clinical Trials (LB), Division of Cancer Treatment and Diagnosis (RFL), and Center for Cancer Research (WHW), National Cancer Institute, National Institute of Health, Bethesda, MD; Division of Oncology, University of Washington, Seattle WA (DGM); British Colombia Cancer Agency, Vancouver, BC (LHS); Department of Medicine, University of Virginia, Charlottesville, VA (MEW); Department of Medicine, Weil Cornell University, New York, NY (JPL); Department of Medicine, University of Chicago, Chicago, IL (SMS) nowakowski.grzegorz@mayo.edu.
Abstract:
Diffuse large B cell lymphoma (DLBCL) comprises multiple molecular and biological subtypes, resulting in a broad range of clinical outcomes. With standard chemoimmunotherapy, there remains an unacceptably high treatment failure rate in certain DLBCL subsets: activated B cell (ABC) DLBCL, double-hit lymphoma defined by the dual translocation of MYC and BCL2, dual protein-expressing lymphomas defined by the overexpression of MYC and BCL2, and older patients and those with central nervous system involvement. The main research challenges for DLBCL are to accurately identify molecular subsets and to determine if specific chemotherapy platforms and targeted agents offer differential benefit. The ultimate goal should be to maximize initial cure rates to improve long-term survival while minimizing toxicity. In particular, a frontline trial should focus on biologically defined risk groups not likely to be cured with cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab (R-CHOP). An additional challenge is to develop effective and personalized strategies in the relapsed setting, for which there is no current standard other than autologous stem cell transplantation, which benefits a progressively smaller proportion of patients. Relapsed/refractory DLBCL is the ideal setting for testing novel agents and new biomarker tools and will require a national call for biopsies to optimize discovery in this setting. Accordingly, the development of tools with both prognostic and predictive utility and the individualized application of new therapies should be the main priorities. This report identifies clinical research priorities for critical areas of unmet need in this disease.
