The Annual Meeting of the American Society of Hematology (ASH) was held on 7−10 December 2019 in Orlando (FL, USA). The top Italian hematologists then gathered in a post-ASH conference to discuss the data, guidelines and news presented at the conference.
This meeting is key for Italian specialists to draw conclusions of what has been done so far and, of course, to set the new starting points for future work and research.
Here, we report the interview by Professor Falanga at the post-ASH meeting held on 13−15 February 2020 in Naples (Italy).
Professor Falanga summarizes the main studies and discusses the specific clinical settings in which the administration of lower doses of oral anticoagulants are recommended. Special attention is dedicated to the management of prolonged therapy, which is necessary for patients who experience venous thromboembolism.
She emphasizes the recommendation by the guidelines relating to the new oral anticoagulants used for prophylaxis of oncologic patients undergoing chemotherapy as major news, along with the use of low-molecular-weight heparin.
Moreover, Professor Falanga directs attention to studies regarding antiphospholipid antibodies, which is a very innovative field in the treatment of a rare disease, the Catastrophic Syndrome. Professor Falanga also details her satisfaction concerning the scientific discussion in the hematological field and the constant research for the best anticoagulant to treat thrombosis.
Professor Falanga, in your report, you have explained that one of the most discussed issues of this year at ASH is the use of lower doses of oral anticoagulants. Could you please tell us in detail what has emerged from the discussion?
“I am referring to direct oral anticoagulants, i.e., the new inhibitors of factor X and factor II. The tendency is to design trials with drugs at lower doses, clearly with the aim to reduce the adverse events associated with anticoagulant therapy, which is obviously bleeding. This year, a lot has been done in terms of the ASH program dedicated to thrombosis. The new ASH guidelines on venous thromboembolism have also been presented.
In particular, what has been done so far in the application of lower doses in the therapy has been clarified, and the feedback emerged from recent clinical studies in this regard has also been commented upon. The attention focused not only to the use of the lower doses of new anticoagulants but, in general,on the doses used in normal prophylaxis of the different settings of thrombosis pathologies. Moreover, we can see that primary prophylaxis is of most interest to orthopedic surgery patients. In this setting, the studies show that the bleeding occurring is mainly minor, and the new anticoagulants are, by now, comparable to the low-molecular-weight heparin, to Fondaparinux and the other drugs routinely administered.
In the setting of primary prophylaxis of patients from the Department of Internal Medicine, where the studies mostly include drugs and molecules that inhibit factor Xa, such as rivaroxaban and apixaban, the results are less brilliant, due to an increment of bleeding events. Nevertheless, these studies show non-inferiority of the new drugs with respect to the compared one.
The most satisfying result has been obtained in prolonged therapy for venous thromboembolism. It is known that in the case of an acute event, the therapeutic dose will be given for 6 months or up to 1 year, especially in the case of pulmonary embolism. After 1 year, in idiopathic cases and in case of a first event, there is a wide undefined area within which the clinician has difficulty in making decisions on the basis of clinical trials. The aim is to find a non-detrimental long-term therapy, longer than 12 months, that will not result in bleeding events. There are two studies evaluating this situation, the Einstein Choice, testing rivaroxaban, and the Amplify Extension with apixaban. Both of the studies have demonstrated that administration of low doses of these drugs for up to 1 year after the acute event gives a good result in terms of reduction of relapses without the concomitant increment of thrombosis events. These studies are the basis for the future research for even lower therapeutic doses.
Moreover, there is always a deep interest in potential new anticoagulants that have different molecules as a target, such as factor XI or polyphosphates. There is wide research in this direction, for the best anticoagulant that inhibits thrombosis but, at the same time, allows avoidance of bleeding events. To find such a molecule is the dream of every researcher.”
Another important topic discussed is venous thromboembolism in cancer patients. What is the state of the art?
“We have discussed the most recent trials that suggest the type of prophylaxis for patients with high thrombotic risks and undergoing chemotherapy. Before these trials, for high-risk patients, the only drug considered was low-molecular-weight heparin. From now on, the new oral anticoagulants can be also considered for these patients’ prophylaxis.
In addition, the new oral anticoagulants are now recommended, as well as heparin for therapy. A major news: ASCO and other societies have recently updated their guidelines introducing the recommendation for the new anticoagulant drugs.”
Professor Falanga, you have also explained that some interesting studies about antiphospholipid antibodies have been presented. What exactly are these studies about and what do they tell us?
“The studies regarding antiphospholipid antibodies are one of the most fascinating topics of coagulation as they are related to a very specific setting, a rare disease. Antiphospholipid antibodies are under investigation, and there is still debate around the therapeutic approach. Recent data would indicate a novelty in this area, but more than anything else, the idea that the immunosuppressive approach is important for these patients is making its way. This happens especially in the case of the Catastrophic Syndrome, a rare syndrome with a high mortality rate, which is the worst expression of the Antiphospholipid Antibody Syndrome. In the plenary session, a new study that shows a very strong implication for the role of complement has been presented. For those who develop the Catastrophic Syndrome, there are precise mutations that allow identification of the patients at risk to have the catastrophic phase. The research in this direction will surely bring a lot of results.”
Which is, in your opinion, the most important message delivered by the ASH concerning thrombosis?
“I think that ASH 2019 has been the one with the widest scientific presence in the thrombotic field, also in terms of guidelines as I mentioned before. Therefore, I believe there is a high interest in the hematological field which is growing towards the non-oncologic pathologies too.”
The interview by Professor Falanga can also be heard (in Italian) on the Pharmastar website.