VTE prophylaxis: Real-world practices and IFM clinical guidelines

Venous thromboembolic events (VTE) are commonly associated with multiple myeloma (MM) and can have detrimental effects such as treatment discontinuation, increased bleeding, and long-term complications that all negatively impact prognosis. The cause of VTE in MM is not fully understood; however, an association has been observed between immunomodulatory agent (IMiD)-based therapies in combination with dexamethasone, as well as inappropriate use of thromboprophylaxis.¹

To more investigate the causative contributions of these factors, the Intergroupe Francophone du Myélome (IFM) conducted a large survey for clinicians regarding their current thromboprophylaxis practices, and used this to develop guideline recommendations for thromboprophylaxis of patients with MM.

The Multiple Myeloma Hub is pleased to summarize the results of this survey and the IFM clinical guidelines below.

Results of the survey¹

• In total, 84 clinicians were surveyed across France and Belgium with the majority (83.3%) being hospital practitioners from a variety of practice settings. Overall, 98.8% of responders considered thromboprophylaxis important in patient care
• Most clinicians (70.9%) opted to continue with thromboprophylaxis until the end of IMiD-based therapy in both first line and relapsed/refractory settings
• Two thirds of participants also indicated that they would still prescribe thromboprophylaxis when a non IMiD-based treatment was chosen

The considerations clinicians made for practice before initiating thromboprophylaxis are outlines in Figure 1.

Figure 1. Survey results on the considerations before initiating thromboprophylaxis* 

IMiD, immunomodulatory agent; IMWG, International Myeloma Working Group; VTE, venous thromboembolic event.
*Data from Frenzel, et al.¹

Antithrombotic drugs dosing and administration¹

• The preferred antithrombotic thromboprophylaxis was direct oral anticoagulants (DOAC), followed by low-molecular-weight heparin (LMWH), and then aspirin
• Overall, 13% had never considered DOAC thromboprophylaxis
• Overall, 15% stated they never prescribe aspirin but among those who did, 75 mg daily dose was preferred
• The majority of patients did not receive any additional anticoagulation therapy, and when given it was preferentially given under cardiac supervision
• Two thirds of clinicians prescribed enoxaparin 0.4 mL vs one third who prescribed <175 IU/Kg tinzaparin daily
• In total, 78% preferred prescribing 2.5 mg apixaban twice a day vs 18% who preferred 10 mg rivaroxaban daily

The justifications for not prescribing each drug class include:

• LMWH; administered via subcutaneous route leading to difficulties in patients after extended treatment, as well as their use in patients with severe renal failure.
• DOACs; concerns regarding lack of approval in MM, risk of bleeding, absence of antidote, and renal impairment.

IFM clinical guidance¹

With the aim to improve thromboprophylaxis in patients with MM, the IFM developed an algorithm to aid in clinical decision-making. This algorithm is presented in Figure 2.

Figure 2. IFM clinical recommendations for thromboprophylaxis initiation* 

BID, twice daily; CrCL, creatinine clearance; DOAC, direct oral anticoagulant; IMiD, immunomodulatory agent; IMWG, International Myeloma Working Group; IU, international unit; LMWH, low-molecular-weight heparin; OD, once daily; PRISM, Precision Intervention Smoldering Myeloma; VTE, venous thromboembolism.
*Adapted from Frenzel, et al.¹

The choice of an IMiD-dexamethasone-based therapy emerged as the key factor to initiating the decision algorithm, based on published data showing that the risk of VTE is up to 25% higher in those being treated with IMiDs, particularly in combination with dexamethasone. Alongside existing therapy, there are several highlighted risk factors including renal impairment and bleeding risks, which are also associated with a higher likelihood of VTEs.

Of note in the IFM report, aspirin is described as an inappropriate thromboprophylactic agent that should not be considered. This is due to trial data, such as that in the MELISSE study which found that VTEs were observed in 7% of patients treated with aspirin vs 3% of patients treated with LMWH. Furthermore, in an additional trial, 1.7% of patients treated with aspirin were diagnosed with a pulmonary embolism compared with zero in the LMWH group.

Conclusions

There are inconsistencies in current real-world treatment practices for VTE prophylaxis, highlighting a need for better understanding and clearer clinical guidelines. The IFM highlights that the consideration of VTE prophylaxis is vital for all patients being treated with IMiDs in combination with dexamethasone and other key risk factors including renal failure or bleeding risk.

This novel algorithm can help guide treatment decisions. However, it is important to note that in-depth clinical trials on the implementation of this guidance are lacking, and to further improve treatment guidelines and patient outcomes, long-term follow-up, and a better understanding of VTEs in MM is required.