From the Guidelines
Lenalidomide can potentially cause or worsen heart failure in some patients, particularly those with pre-existing cardiac conditions, as evidenced by the phase III ENDURANCE trial which showed an increased risk of heart failure with carfilzomib/lenalidomide/dexamethasone compared to bortezomib/lenalidomide/dexamethasone 1.
Key Considerations
- Patients taking lenalidomide should be monitored for signs of heart failure, including shortness of breath, rapid weight gain, swelling in the extremities, and unusual fatigue.
- The risk of heart failure appears higher in patients with prior cardiac disease, those receiving high cumulative doses, or patients with additional risk factors such as hypertension or diabetes.
- Cardiac monitoring before and during treatment is recommended, especially for high-risk patients, as seen in the carfilzomib/lenalidomide/dexamethasone with autologous HCT study where cardiac adverse events were 4% for all grades (0% grade 3/4) 1.
Management and Prevention
- If heart failure develops while on lenalidomide, dose reduction, temporary interruption, or permanent discontinuation may be necessary depending on severity.
- Alternative treatments may be considered for patients with significant cardiac history or those who develop cardiac complications on lenalidomide.
- Patients should promptly report any new cardiac symptoms to their healthcare provider, as early intervention can prevent progression to severe heart failure.
Mechanism and Risk Factors
- The mechanism behind lenalidomide-induced heart failure is not fully understood but may involve direct cardiotoxicity, fluid retention, or exacerbation of underlying cardiovascular conditions.
- The presence of other risk factors such as hypertension, dyspnea, and acute kidney injury, as seen in the ENDURANCE trial, should be carefully evaluated when considering lenalidomide treatment 1.
From the Research
Lenalidomide and Heart Failure
- Lenalidomide has been associated with cardiovascular toxicity, including heart failure, as reported in a case study where an 85-year-old woman developed congestive heart failure after starting lenalidomide and dexamethasone therapy 2.
- The study suggests that lenalidomide may cause drug-induced myocarditis, and patients presenting with signs and symptoms of heart failure should be considered for a myocardial biopsy if other common causes of heart failure are excluded 2.
- Another study highlights the importance of monitoring patients for cardiovascular complications, including heart failure, when treated with lenalidomide, especially in those with underlying cardiovascular risk factors or disease 3.
Cardiovascular Complications of Lenalidomide
- Lenalidomide has been shown to increase the risk of cardiovascular complications, including cardiomyopathy, heart failure, accelerated hypertension, arrhythmias, and thromboembolism 3, 4.
- The risk of thrombosis with lenalidomide can be mitigated with the use of antithrombotic agents, such as aspirin, although the evidence for its effectiveness is based on "before/after" and retrospective studies 5.
- Lenalidomide has also been associated with cardiac arrhythmias, such as atrial fibrillation, and severe hematological disorders, including neutropenia, thrombocytopenia, and anemia 4, 6.
Management of Lenalidomide-Associated Heart Failure
- A reasonable management approach for lenalidomide-associated heart failure is drug discontinuation and early institution of corticosteroid therapy 2.
- Patients treated with lenalidomide should be closely monitored for signs and symptoms of heart failure, and a myocardial biopsy should be considered if other common causes of heart failure are excluded 2.
- Collaboration between cardiologists and oncologists is necessary to ensure patients receive optimal cancer treatment while minimizing cardiovascular risk 3.