Managing thrombosis in multiple myeloma: Expert recommendations

The approval of novel therapeutic agents for multiple myeloma (MM), including proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, has improved patient outcomes.¹ However, the introduction of these agents has also altered the frequency and epidemiology of thrombotic events. Thrombosis currently represents a significant cause of morbidity and mortality in patients with MM, and thromboprophylaxis is suboptimal.¹

The Multiple Myeloma Hub previously reviewed the risks of thrombosis and the recommended thromboprophylaxis in MM. Here, we summarize practical aspects of recommendations for thrombotic risk factors and risk stratification, primary thromboprophylaxis, management of acute thrombotic events, and secondary thromboprophylaxis, as published by an expert panel in Haematologica.¹

Thrombohemorrhagic risk factors and risk stratification

All patients with MM who are candidates for treatment require a thrombosis risk evaluation to prevent thromboembolic complications. Evaluations should include patient, disease, and treatment-related risk factors (Figure 1).

Figure 1. Key thrombosis risk factors in MM* 

MM, multiple myeloma; VTE, venous thromboembolism.
*Adapted from De Stefano, et al.¹

There are insufficient data to recommend one specific risk assessment model in clinical practice. Application of a risk assessment model should be consistent for all patients in a single center.

In addition to thrombotic risk assessment, bleeding risk should be assessed before initiation of anti-myeloma therapy.

• An accurate patient history should be obtained, and bleeding history investigated.
• Prothrombin time, partial thromboplastin time, platelet count, and fibrinogen level should be evaluated.
• Patients with primary diagnostic test results indicative of a bleeding predisposition, or with a history of bleeding, should be evaluated by secondary diagnostic tests in cooperation with a coagulation expert.

Primary antithrombotic prophylaxis in patients with MM

All patients with MM eligible for anti-myeloma treatment should be considered for thromboprophylaxis. Thromboprophylaxis type, intensity, and duration should be tailored according to individual baseline thrombotic and hemorrhagic risk profiles. Contraindications for thromboprophylaxis are shown in Figure 2.

Figure 2. Contraindications for thromboprophylaxis* 

*Adapted from De Stefano, et al.¹

Considerations for determining appropriate primary antithrombotic prophylaxis in selected patient subpopulations are outlined in Figure 3.

Figure 3. Considerations for primary antithrombotic prophylaxis in selected patient subpopulations with MM*

BMI, basal metabolic index; MM, multiple myeloma.
*Adapted from De Stefano, et al.¹

• Thromboprophylaxis should be prescribed to all other patients, with low molecular weight heparin as the preferred initial option.
• Thromboprophylaxis duration should be modulated according to anti-myeloma treatment duration and evolving risk factors.
  • Prophylaxis should continue whilst thrombosis presents a risk (e.g., active disease or assumption of drugs with a thrombotic risk).
• Primary thromboprophylaxis should be stopped in case of major or clinically relevant bleeding.
  • In this circumstance, the cause of bleeding should be evaluated and corrected before reinitiating thromboprophylaxis.
• Other considerations include drug–drug interactions and patient preference and compliance.

Early treatment of acute thrombotic events, secondary antithrombotic prophylaxis, and re-exposure to anti-myeloma drug in patients with MM

In general, acute thrombosis treatment during active MM treatment should not differ from standard recommendations. Considerations for determining appropriate secondary antithrombotic prophylaxis in selected patient subpopulations are outlined in Figure 4.

Figure 4. Considerations for secondary antithrombotic prophylaxis in selected patient subpopulations* 

MM, multiple myeloma; VTE, venous thromboembolism.
*Adapted from De Stefano, et al.¹

Conclusion

De Stefano et al. provide general recommendations for thrombosis management in MM, as well as recommendations for key patient subpopulations. The expert panel advise that all patients with MM requiring treatment should receive a thrombosis risk evaluation to prevent thromboembolic complications. The evaluation should include patient, disease, and treatment-related risk factors, and concomitant bleeding risk assessment. Recommendations for primary antithrombotic prophylaxis, early treatment of acute thrombotic events, secondary antithrombotic prophylaxis, and re-exposure to anti-myeloma drugs are based on patient profile. These recommendations aim to minimize the risk of thrombosis and maximize treatment adherence in patients with MM who require active treatment.