What is the use and side effects of Thalidomide (generic name)

From the Guidelines

Thalidomide is an effective treatment for multiple myeloma, with a partial response rate of 42% in patients with smoldering multiple myeloma, as reported by Barlogie et al 1. The use of thalidomide in multiple myeloma is supported by its antiangiogenic properties, which interact with the bone marrow microenvironment to inhibit the growth of myeloma cells.

• The action of thalidomide is dependent on the homing of myeloma cells in the bone marrow, making it a suitable treatment for diseases like smoldering multiple myeloma (SMM) with no extramedullary spread.
• Two phase II trials demonstrated a partial response rate of 34% and 36%, respectively, with toxicity consisting of peripheral neuropathy, somnolence, fatigue, and constipation 1.
• A more recent phase II trial by Barlogie et al reported a partial response rate of 42% at four years from enrollment, with median times to response of 1 to 2 years and a median time to progression of 7 years 1.
• However, the development of peripheral neuropathy is a major concern in long-term thalidomide therapy, with dose reduction in 86% and drug discontinuation in 50% of patients 1.
• Therefore, thalidomide should be used with caution and under close monitoring for side effects, particularly peripheral neuropathy, to maximize its benefits in treating multiple myeloma.

From the FDA Drug Label

POMALYST is a thalidomide analogue Thalidomide is a human teratogen, inducing a high frequency of severe and life-threatening birth defects such as amelia (absence of limbs), phocomelia (short limbs), hypoplasticity of the bones, absence of bones, external ear abnormalities (including anotia, micropinna, small or absent external auditory canals), facial palsy, eye abnormalities (anophthalmos, microphthalmos), and congenital heart defects. Pomalidomide was teratogenic in both rats and rabbits when administered during the period of organogenesis. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk to a fetus. If pregnancy does occur during treatment, immediately discontinue the drug.

Thalidomide is a human teratogen and can cause severe birth defects.

• Key points:
  • Thalidomide can cause embryo-fetal harm when administered to a pregnant female.
  • Thalidomide is contraindicated during pregnancy.
  • If pregnancy occurs during treatment, the drug should be discontinued immediately. 2

From the Research

Thalidomide Overview

• Thalidomide is a drug with a history of use as a sedative and antiemetic, but it was banned due to its association with birth defects 3.
• It has resurfaced as a treatment for various immunologic disorders, including erythema nodosum leprosum (ENL), for which it is FDA-approved 3.
• Thalidomide has also been used to treat multiple myeloma, both as a single agent and in combination with other drugs 4, 5.

Mechanism of Action and Effects

• Thalidomide has anti-inflammatory, immunomodulatory, and antiangiogenic properties 3, 4.
• It inhibits tumor necrosis factor alpha (TNF-alpha) and has been shown to be effective in treating ENL and multiple myeloma 3, 5.
• Thalidomide has also been used to treat other conditions, including cachexia related to cancer, tuberculosis, and human immunodeficiency virus infection, although evidence of efficacy is inconclusive 3.

Safety and Adverse Effects

• Common adverse effects of thalidomide include somnolence, constipation, and rash 3.
• Thalidomide-induced neuropathy and idiopathic thromboembolism are critical causes for drug discontinuation 3.
• Thalidomide is contraindicated in pregnant women, women of childbearing age, and sexually active men not using contraception 3.
• A study comparing thalidomide and lenalidomide found that lenalidomide initiators had a reduced risk of peripheral neuropathy compared to thalidomide initiators 6.

Comparison with Other Drugs

• Lenalidomide and pomalidomide are second-generation immunomodulatory drugs (IMiDs) that were created by chemical modification of thalidomide to reduce toxicity and enhance therapeutic activity 4.
• A study found that thalidomide and lenalidomide are equivalent with respect to survival outcomes but different with respect to neurotoxicity in clinical practice settings 6.
• Bortezomib, a proteasome inhibitor, is also used to treat multiple myeloma and can cause peripheral neuropathy, similar to thalidomide 7.