What's Old is New: The Past, Present and Future Role of Thalidomide in the Modern-Day Management of Multiple Myeloma

Abstract

Immunomodulatory drugs (IMiDs) have become an integral part of therapy for both newly diagnosed and relapsed/refractory multiple myeloma (RRMM). IMiDs bind to cereblon, leading to the degradation of proteins involved in B-cell survival and proliferation. Thalidomide, a first-generation IMiD, has little to no myelosuppressive potential, negligible renal clearance, and long-proven anti-myeloma activity. However, thalidomide's adverse effects (e.g., somnolence, constipation, and peripheral neuropathy) and the advent of more potent therapeutic options has led to the drug being less frequently used in many countries, including the US and Canada. Newer-generation IMiDs, such as lenalidomide and pomalidomide, are utilized far more frequently. In numerous previous trials, salvage therapy with thalidomide (50-200 mg/day) plus corticosteroids (with or without selected cytotoxic or targeted agents) has been shown to be effective and well-tolerated in the RRMM setting. Hence, thalidomide-based regimens remain important alternatives for heavily pretreated patients, especially for those who have no access to novel therapies and/or are not eligible for their use (due to renal failure, high-grade myelosuppression, or significant comorbidities). Ongoing and future trials may provide further insights into the current role of thalidomide, especially by comparing thalidomide-containing regimens with protocols based on newer-generation IMiDs and by investigating thalidomide's association with novel therapies (e.g., antibody-drug conjugates, bispecific antibodies, and chimeric antigen receptor T cells).