Thrombosis in multiple myeloma: risk stratification, antithrombotic prophylaxis, and management of acute events. A consensus-based position paper from an <i>ad hoc</i> expert panel

Abstract

The introduction of new therapeutic agents in multiple myeloma (MM), including proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, has improved the outcomes of patients but, in parallel, has changed the frequency and epidemiology of thrombotic events. Now, thrombosis is a significant cause of morbidity and mortality in MM patients, and optimal thromboprophylaxis is far from being reached. Moving from the recognition that the above issue represents an unmet clinical need, an Expert Panel assessed the scientific literature and composed a framework of recommendations for improving thrombosis control in patients candidates for active treatment for MM. The Panel generated clinical key questions using the criterion of clinical relevance through a Delphi process. It explored four domains, i.e., thrombotic risk factors and risk stratification, primary thromboprophylaxis, management of acute thrombotic events, and secondary thromboprophylaxis. The issued recommendations may assist hematologists in minimizing the risk of thrombosis and guarantee adherence to treatment in patients with MM candidates to active treatment.

Approach to Contemporary Risk Assessment, Prevention and Management of Thrombotic Complications in Multiple Myeloma

“…Based on these findings, the IMPEDE-VTE and the SAVED models are preferentially recommended for utilization in the latest guidelines [ 86 ]. However, as Stefano et al argue in their latest consensus paper [ 9 ], there are insufficient data to recommend one specific RAM over the other in clinical practice. We should also note that both IMPEDE-VTE and SAVED scores were developed using patients who received treatment mostly before the era of novel agent availability used currently in clinical practice.…”

“…The type, intensity and duration of thromboprophylaxis should be patient-specific and tailored to each patient’s baseline thrombotic and hemorrhagic risk [ 9 ]. Important issues when considering the mode of thromboprophylaxis include, of course, effectiveness, but also the route of administration, patient convenience—one should opt for the least intrusive method and safety in the context of frailty—age, cyclical thrombocytopenias, minimizing bleeding risk and impaired renal function.…”

“…Other options for these patients include rivaroxaban 10 mg daily, apixaban 2.5 mg twice daily, fondaparinux 2.5 mg daily and warfarin (target INR 2-3). In a recent consensus paper, Stefano et al [ 9 ] recommend that patients who are low risk for thrombosis should receive no thromboprophylaxis or low-dose aspirin. According to a consensus paper, prophylactic-dose LMWH should be the first choice for all other patients.…”

“…Based on current guidelines, when a VTE event occurs in patients with MM, the bleeding risk should be assessed, and patients should receive anticoagulation for at least six months [ 86 ]. De Stefano et al’s recently published consensus paper summarizes recommendations for treating acute thrombotic events and secondary antithrombotic prophylaxis [ 9 ]. In the case of ongoing treatment with IMiDs, indefinite thromboprophylaxis should be considered.…”

“…The International Myeloma Working Group (IMWG) [ 7 ], the European Myeloma Network (EMN) and the National Comprehensive Cancer Network (NCCN) [ 8 ] have published guidance on the prevention of MM-associated thrombosis. A consensus-based position paper was also released earlier this year [ 9 ]. Appropriate risk identification for VTE is advocated for optimal care of patients with MM, and central to the framework of international guidelines is the ability to appropriately risk stratify MM patients for VTE.…”