What is the use and mechanism of Thalidomide?

From the Guidelines

Thalidomide should be used with caution in patients with multiple myeloma, in combination with dexamethasone, due to its increased toxicity, specifically deep vein thrombosis (DVT), and other side effects such as rash, gastrointestinal disturbance, peripheral neuropathy, or somnolence, as reported by Rajkumar et al. 1. When considering thalidomide as a treatment option, it is essential to weigh the benefits of the higher response rate against the potential risks and side effects. The use of thalidomide requires individual patient consideration, and appropriate thromboprophylaxis is recommended to mitigate the risk of DVT 1. Some key points to consider when using thalidomide include:

• Thalidomide attacks multiple targets in the microenvironment of the myeloma cell, producing effects such as apoptosis and inhibition of angiogenesis and cytokine circuits 1
• The response rate to the combined therapy of thalidomide and dexamethasone was significantly higher compared with that for dexamethasone alone (63% vs. 41%, respectively) 1
• Increased toxicity is associated with thalidomide, specifically DVT, and therefore prophylactic anticoagulation is recommended if thalidomide and dexamethasone are given 1
• Other side effects of thalidomide included rash, gastrointestinal disturbance, peripheral neuropathy, or somnolence 1
• The panel recommends appropriate thromboprophylaxis for patients undergoing this therapy 1

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Thalidomide Overview

• Thalidomide is a drug with a history of use and controversy, initially withdrawn from the market due to its association with congenital abnormalities 2.
• It has been approved by the FDA for the treatment of erythema nodosum leprosum and has shown promise in cancer therapy, particularly in multiple myeloma 3, 2.

Thalidomide in Multiple Myeloma

• Thalidomide has demonstrated significant activity in all phases of multiple myeloma, exerting its effects through antiangiogenesis, immunomodulation, and induction of apoptosis in tumor cells 4.
• The combination of thalidomide and dexamethasone has shown remarkable activity in treating both newly diagnosed and relapsed myeloma, with overall response rates of approximately 70% in newly diagnosed patients 4.
• However, this combination is associated with an increased risk of deep vein thrombosis, necessitating routine prophylactic anticoagulation 4.

Adverse Effects of Thalidomide

• Common adverse effects of thalidomide include somnolence, constipation, rash, peripheral neuropathy, and thromboembolism 3, 2.
• The incidence and severity of adverse events are related to the dose and duration of therapy, with doses of 200 mg/day or less usually being well tolerated 3.
• Thalidomide also has a teratogenic effect, which has been well documented, and its use is strictly regulated due to this risk 5, 2.

Comparison with Lenalidomide

• Lenalidomide, a structural analogue of thalidomide, is licensed for the treatment of multiple myeloma in combination with dexamethasone after failure of the initial treatment regimen 5.
• Lenalidomide has a different side effect profile compared to thalidomide, with a lower risk of peripheral neuropathy but a higher risk of cardiac arrhythmias and severe hematological disorders 5.
• The risk-benefit balance of lenalidomide compared to thalidomide or bortezomib is not well established, with no evidence that lenalidomide has a more favorable risk-benefit balance in patients with relapsed or refractory multiple myeloma 5.