What is an alternative to Lenalidomide (lenalidomide) in a patient with overt heart failure who is currently using Velcade (bortezomib), Revlimid (lenalidomide), and Dexamethasone (dexamethasone) (VRD)?

From the Guidelines

For patients with overt heart failure who are on VRD (Velcade/bortezomib, Revlimid/lenalidomide, dexamethasone) therapy, lenalidomide should be replaced with pomalidomide, creating a VPD regimen (Velcade, pomalidomide, dexamethasone), as suggested by the study 1. The typical dosing would be pomalidomide 4 mg orally from day 1 through 21, bortezomib 1.3 mg/m² subcutaneously on days 1,8,15, and 22, and dexamethasone 20-40 mg weekly, with cycles repeated every 28 days. Lenalidomide is contraindicated in patients with significant heart failure due to its fluid retention properties and increased risk of thromboembolic events, which can worsen cardiac function. Pomalidomide provides an effective alternative with less cardiac toxicity while maintaining efficacy against multiple myeloma, as shown in the study by Chari et al 1, where the combination of daratumumab, pomalidomide, and dexamethasone (DPd) was associated with a response rate of 58% in heavily pretreated patients. Careful cardiac monitoring should continue during therapy, including regular assessment of ejection fraction, symptoms, and fluid status. Dose adjustments may be necessary based on the patient's renal function, as pomalidomide is renally cleared. Additionally, prophylactic antiviral therapy should be maintained to prevent herpes zoster reactivation, which is a risk with bortezomib-containing regimens. Some key points to consider when replacing lenalidomide with pomalidomide include:

• The patient's previous response to lenalidomide and bortezomib
• The presence of any other comorbidities, such as renal impairment or thrombocytopenia
• The potential for increased toxicity with the new regimen, such as infusion reactions with daratumumab
• The need for ongoing cardiac monitoring and dose adjustments as necessary. It is also important to note that the study 1 recommends that patients who have disease that is refractory to IMiDs should be treated with DVd, and if refractory to PI, they should be treated with DRd, but in the context of overt heart failure, the replacement of lenalidomide with pomalidomide is a more suitable option.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Lenalidomide Replacement in Patients with Overt Heart Failure

• In patients with multiple myeloma and overt heart failure, the replacement of lenalidomide in the VRd regimen (bortezomib, lenalidomide, and dexamethasone) is a consideration due to the potential cardiotoxic effects of lenalidomide 2.
• A case report highlighted the development of severe systolic heart failure in a patient with multiple myeloma after treatment with a cyclophosphamide, bortezomib, and dexamethasone regimen, emphasizing the need for thorough cardiovascular assessment before and during chemotherapy 2.
• The management of overt congestive heart failure involves normalization of loading conditions and myocardial inotropy, with pharmacological agents such as diuretics, digitalis, and vasodilators playing a crucial role 3, 4.
• In the context of multiple myeloma treatment, the use of alternative regimens such as daratumumab, cyclophosphamide, bortezomib, lenalidomide, and dexamethasone (Dara-CVRd) has shown promise in improving outcomes for ultra-high-risk patients 5.
• However, the replacement of lenalidomide in the VRd regimen for patients with overt heart failure would require careful consideration of the potential benefits and risks, as well as alternative treatment options 6, 2, 5.

Treatment Options for Heart Failure

• Diuretics, digitalis, and vasodilators are commonly used to manage congestive heart failure, with ACE inhibitors and angiotensin II receptor blockers playing a key role in improving prognosis 3, 4.
• The use of beta-blockers and spironolactone may also be beneficial in certain patients with heart failure 4.
• In the context of multiple myeloma, the choice of treatment regimen should take into account the patient's cardiovascular risk factors and the potential cardiotoxic effects of certain agents 2, 5.

Multiple Myeloma Treatment Regimens

• The VRd regimen (bortezomib, lenalidomide, and dexamethasone) is a standard therapy for newly diagnosed multiple myeloma, but may not be suitable for patients with overt heart failure due to the potential cardiotoxic effects of lenalidomide 6, 2.
• Alternative regimens such as Dara-CVRd (daratumumab, cyclophosphamide, bortezomib, lenalidomide, and dexamethasone) may be considered for patients with ultra-high-risk multiple myeloma, but require careful evaluation of the potential benefits and risks 5.
• The choice of treatment regimen should be individualized based on the patient's specific needs and risk factors, with careful consideration of the potential cardiotoxic effects of certain agents 6, 2, 5.