ASH News Daily - Tuesday, December 13, 2011 - (Page A-6)

Page A–6 ® MARROW FAILURE Bone Marrow Failure: Success May Be on the Horizon Diamond-Blackfan anemia (DBA) By BaRBaRa pRo, Md T he Education Program session, “Understanding and Management of Inherited Bone Marrow Failure Syndromes,” included three presentations that focused on dyskeratosis congenita (DC), Diamond-Blackfan anemia, and Fanconi anemia. We all had to familiarize ourselves again with these rare but very instructive disorders. The first speaker, Dr. Inderjeet Dokal, Barts and The London School of Medicine and Dentistry, also chair of this session, presented an update on DC, a syndrome characterized in the classic form by bone marrow failure, mucocutaneous abnormalities, and predisposition to develop cancer, with the latter being the most common cause of mortality. “Clinical diagnosis of DC is difficult as there are different faces of DC,” said Dr. Dokal. What do we know so far? Eight genes have been found to be associated with this disease and nearly all of them (7 out of 8) are involved in telomere maintenance (the DNA tails). A number of other disorders including aplastic anemia, myelodysplastic syndromes, and leukemia are also associated with defective telomere maintainance. Dr. Dokal remarked, “We need to increase physician awareness and recognize that a multidisciplinary approach is needed to treat these patients.” Multiple Myeloma «« From Page A-3 #631) from the University of Michigan, Ann Arbor, showed that carfilzomib may be just as potent in the front line setting with 100 percent of patients achieving VGPR over time. With a distinct toxicity profile, this agent may be better tolerated over the long term. Dr. Pieter Sonneveld (abstract #633) from Erasmus Medical Center, Rotterdam, Netherlands, confirmed the significant activity of the second-generation proteasome inhibitor and its tolerance when given as maintenance. In addition, the preliminary clinical activity and side effect profile of the newest proteasome inhibitor, MLN 9708 (abstract #301), an oral agent, was presented by Dr. Richardson, who demonstrated 13 percent (> PR) single-agent activity, although the one complete response was in a bortezomib naive patient. According to Dr. Jesus G. Berdeja, from the Sarah Cannan Research Institute, Nashville, Tennessee, MLN9708 in combination with lenalidomide and is another rare but important congenital disease, characterized among physical abnormalities by red cell aplasia and increased risk of cancer. There is accumulating evidence of abnormalities in ribosome biogenesis in DBA. Dr. Sarah Ball, St. George’s University of London, summarized the clinical and genetic features of this rare disease and concluded that despite the “explosion of knowledge” in this field, it has done little thus far to effect change in clinical management. Lastly, Dr. Jean Soulier, Saint- Louis Hospital and University Paris-Diderot, France, gave a detailed update on Fanconi anemia (FA). FA is a rare genetic disorder characterized by progressive bone marrow failure during childhood. “Early and accurate FA diagnosis is crucial,” said Dr Soulier. As many as 15 genes (and counting) have been identified to be associated with this complex disease. If you missed this education ses- sion, plan to attend the Presidential Symposium this morning at 9:45 a.m. in Hall AB, San Diego Convention Center. It is chaired by ASH President Dr. J. Evan Sadler. This session will elucidate how analyses of rare disorders can help our understanding of the mechanisms that control hematopiesis and their possible implications in the diagnosis and treatment of these diseases. Dr. dexamethasone in newly diagnosed patients again showed a 100 percent response rate (abstract #479). As an entirely oral regimen, this combination may ultimately prove most desirable. Other innovative strategies to treat relapsed patients that were described include antibody therapy directed against CD138 (abstract #305) or CS1 (abstract #303), an idotype-pulsed dendritic cell vaccine (abstract #636), MEK ½ inhibition (abstract #306), and inhibition of kinesin spindle protein by a selective inhibitor, ARRY-520 (abstract #2935). Finally, Dr. David Siegel, Hackensack University, New Jersey, demonstrated promising results with the HDAC inhibitor vorinostat in combination with bortezomib +/- dexamethasone (abstract #480). Perhaps we can expect more than 31 flavors in the future? Dr. Landau has served on a Mil- lennium advisory board and currently receives research support from Millennium. Dr. Rosenzweig indicated no relevant conflicts of interest. Monica Bessler, The Children’s Hospital of Philadelphia, will begin the session with an update on the role of telomereses in the pathogenesis of bone marrow failure. Short tails can be a sign of age but can also be present in the very young and cause a number of problems. Dr. Benjamin Ebert, Brigham and Women’s Hospital, will give an update on ribosomopathies and THROMBOSIS All Things Anti-Thrombotic By david GaRcia, Md, and ShaRi Ghanny, Md terday was a busy one. In “New Anticoagulants,” an Education Spotlight session chaired by Dr. Elaine Hylek, Boston Medical Center, and Dr. John Heit, Mayo Clinic, Minnesota, attendees heard details from three different landmark clinical trials that have compared warfarin to a novel anticoagulant agent (dabigatran etexilate, rivaroxaban or apixaban, respectively) for the prevention of stroke in patients with non-valvular atrial fibrillation. The presenters provided suggestions regarding the assessment of their dabigatran-associated bleeding and provided insight about how and under what circumstances one might assess dabigatran’s anticoagulant effect. “Dabigatran etexilate and rivaroxaban represent the next generation of oral antithrombotics that have been eagerly awaited since the first reports on vitamin K antagonists (dicoumarol) for the prevention and treatment of thrombosis in 1942. However, these novel antithrombotics have important strengths and weaknesses that clinicians must understand in order to provide optimal management of the individual patient,” said Dr. Heit. Later Monday, several clinically I important papers were presented in a session on antithrombotic therapy and VTE. Dr. Cecilia Becattini, University of Perugia, Italy, shared the results of the Warfasa study, a randomized, double-blinded trial of aspirin as a secondary prevention method for patients with idiopathic VTE. In the trial, 403 patients with unprovoked venous thrombosis were, after 6-18 months of standard anticoagulation, randomly assigned to receive 100 mg of daily aspirin or matching placebo during a median study period of 24.6 months. Not surprisingly, during the first two f you’re interested in the treatment of patients with (or at risk for) clotting disorders, then yes- years of follow-up, the annualized recurrent thrombosis rate was 11.2 percent for the patients taking placebo. However, the rate of recurrent DVT/PE was about 40 percent lower (6.6%) among patients who received aspirin (hazard ratio = 0.57; 95% CI 0.35 to 0.93). There was no difference between the groups in the proportion of patients who experienced bleeding. Two papers, one presented by Dr. Jovana Yudin, McMaster University, and one by Dr. Leslie Skeith, University of Western Ontario, raised new questions about the benefits of peri-procedural anticoagulant (“bridging”) therapy. Dr. Yudin described a meta-analysis of 32 (mostly observational) studies that included data from more than 6,700 patients who interrupted anticoagulation for a procedure. Patients who received bridging treatment had a more than five-fold increased risk for major bleeding. Interestingly, the overall rate of thrombosis was quite low and no difference was seen based on whether patients were “bridged” or not (0.87 vs. 0.77%, respectively). The rates of thrombosis were sim- ilarly low in a study presented by Dr. Leslie Skeith. In this single-institution, observational study more than 400 patients interrupted warfarin more than 600 hundred times to undergo procedures. All patients were taking warfarin to prevent VTE and none had experienced VTE less than three months prior to warfarin interruption. Although bridging therapy was used in only about one-quarter of the patients, the 90day rate of thrombosis was very low at 0.63 percent. Taken together, these studies highlight the need for prospective, randomized controlled trials that will better define the benefits (and risks) of bridging therapy for warfarin-treated patients. Dr. Garcia has served on the advisory boards of Boehringer Ingelheim, Janssen, and Daiichi Sankyo. Dr. Ghanny indicated no relevant conflicts of interest. genetic abnormalities leading to ribosome dysfunction. Lastly, Dr. Alan D’Andrea, Dana-Farber Cancer Institute, will give an overview of Fanconi anemia with special emphasis in the genetic alterations found in this disease and present in other types of cancer. Dr. Pro indicated no relevant conflicts of interest. ASH NEWS DAILY Tuesday, December 13, 2011

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ASH News Daily - Tuesday, December 13, 2011

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