ASH News Daily 2012 - Sunday, December 9, 2012 - (Page A-4)

Page A–4 ® MYELOMA Monoclonals and Their Plasma Cells: Characters in Search of an Author BY JOSE A. BUFILL, MD L ike an exclamation point in a patient’s life story, the monoclonal protein spike draws our attention to a significant statement. Attention must be paid. Is it the first word of an epic tale or a tasteless prank nature plays on an unsuspecting victim? Monoclonal proteins can be either or both, and sorting through the various possible narratives was the task of the speakers at yesterday’s Education Program session, “The Spectrum of Plasma Cell Dyscrasias.” Morie A. Gertz, MD, Mayo Clinic in Roches- ter; Irene Ghobrial, MD, Dana-Farber Cancer Institute in Boston; and Giampaolo Merlini, MD, University of Pavia, Italy, each approached the difficult problem of the monoclonal gammopathy from their own unique perspectives and experience. Finding a monoclonal protein is a rare event. Prevalence rates in general populations across continents barely approach 5 percent. But they are a common reason for referrals to hematologists. And monoclonals always test the skills of experienced clinicians. Dr. Gertz narrated the stories of several interesting patients from his extensive library at the Mayo Clinic to emphasize the difficult diversity of plasma cell dyscrasias. Monoclonals always reflect a clonal disorder, but they don’t always cause a clinical disorder. When they do, they can range from subtle to overwhelming. Hearing these stories should help busy practicing physicians pick out those subtle but serious conditions that might mimic monoclonal gammopathy of undetermined significance (MGUS) at first but soon take on a more aggressive course. Attendees listen to speakers at the Education Program session, “The Spectrum of Plasma Cell Dyscrasias.” Lymphomas «« From Page A-1 treat patients with unfavorable molecular profile? 2) What should we do with an abnormal interim restaging with fluorodeoxyglucose positron emission tomography (FDGPET); how is “abnormal” defined, and should therapy be changed? and 3) In the era of immuno-chemotherapy (e.g., R-CHOP), should DLBCL patients with primary refractory or relapsed disease receive novel therapy rather than autologous stem cell transplantation in the wake of the results of the Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) study? The first question was addressed by Laurie Sehn, MD, of the British Columbia Cancer Agency in Vancouver. Dr. Sehn reviewed pretreatment, clinical, immunohistochemical, and molecular prognostic factors that help guide primary therapy. She discussed how molec- ular profiling may help us identify potential targets for novel therapy and whether it adds any benefit to the IPI. Dr. Moskowitz took on the second question himself. He reviewed the use of FDG-PET in the management of DLBCL, focusing on its utility as a prognostic tool for risk-adapted therapy in the primary as well as the relapsed setting. Finally, Christian Gisselbrecht, MD, of the Hôpital Saint-Louis in Paris, who was one of the lead investigators in the CORAL study, concentrated on the third question. Dr. Gisselbrecht stated that “we may be fighting a losing battle once a patient relapses after primary therapy,” as patients who have already received optimal immuno-chemotherapy possibly receive minimal benefit with high-dose chemotherapy and autologous stem cell transplantation. Using the results of the CORAL study as a platform, he described treatment strategies for patients with primary refractory and Following the traditional threepart classification scheme, Dr. Merlini presented an overview of MGUS in its various permutations: those associated with IgM, non-IgM, and light-chain phenotypes. Each appears to write its own unique story. Patients with IgM and non-IgM MGUS differ in that their respective plasma cell clones develop either before or after isotype switching, respectively. As such, translocations in the immunoglobulin heavy-chain region – 14q32.24 – are seen in about half of the non-IgM patients, but never in those with IgM monoclonals. In patients with IgG or IgA MGUS, the risk for development of multiple myeloma and related disorders is well known. IgM MGUS can be considered a distinct biological entity whose phenotype leads to Waldenström macroglobulinemia (WM). relapsed DLBCL. All of the presenters emphasized that these important questions will not be answered without the willingness of investigators and patients to participate Dr. Ghobrial focused on IgM monoclonals. Like its more common cousin, multiple myeloma, WM often develops from an MGUS clone and smolders through an asymptomatic stage before becoming symptomatic, at times after many years. But the similarity ends there. IgM MGUS seems to be like a character in search of an author. Like lymphoma, malignant cells of WM can infiltrate and enlarge lymph nodes and spleen. Like myeloma, its monoclonal can wreak havoc. An excess of clonal IgMs can cause hemolysis, neuropathy, hyperviscosity, skin rashes, Raynaud phenomenon, and immune thrombocytopenic purpura. They can interfere with laboratory tests and induce coagulopathies. In rare cases, light chains associated with IgM monoclonals can cause amyloidosis, infiltrating the heart and kidneys. Taken together, these three talks illustrated the significant progress attained in understanding the pathogenesis and natural history of these rare but fascinating diseases. We can anticipate that – in the very near future – the stories of most patients with the plasma cell dyscrasias will have a happy ending. If you are interested in checking out this session, it is taking place again tomorrow at 7:00 a.m. in Room A101, Level 1, building A. Dr. Bufill indicated no relevant conflicts of interest. in clinical trials. I think “old blood and guts” would have been proud. Dr. Bishop indicated no relevant conflicts of interest. ASH NEWS DAILY Sunday, December 9, 2012 Dr. Mary Cushman encourages the use of advocacy stickers for business cards at the Grassroots Network Lunch.

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ASH News Daily 2012 - Sunday, December 9, 2012

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