Immunomodulatory drugs in multiple myeloma

Abstract

The introduction of new agents immunomodulatory drugs (IMiDs) and proteasome inhibitors has brought a major shift in therapeutic paradigm in the treatment of newly diagnosed and refractory multiple myeloma (MM). Thalidomide was the first immunomodulatory agent approved for use in myeloma. Although highly active, it is associated with considerable toxicity, particularly in older patients. Lenalidomide, an analog of thalidomide, was developed because of its more potent anti-MM activity and better toxicity profile than the parent compound. Since its introduction in 2004, lenalidomide has established a role in all phases of treatment in MM. The pleiotropic antitumor effects of lenalidomide have translated into clinical efficacy in diseases other than MM. Pomalidomide is a highly potent third-generation IMiD that shares similar pharmacologic properties as thalidomide, with very promising activity in MM and myelofibrosis. This review summarizes the mechanisms of action and clinical activity of IMiDs in MM.

Invasive fungal infections in patients with multiple myeloma: a multi-center study in the era of novel myeloma therapies

“…3,8 This shift could be because IMiDs and PI are inherently less myelosuppressive compared with conventional chemotherapy which now tends to be used in combination for patients with refractory or progressive disease. 12 Cumulative deficits in various arms of the immune system, in particular of cell-mediated immunity due to progressive disease, could also account for our findings. 2 The impact of novel agents and use of ASCT on risk of IFI has not been previously evaluated.…”

Pomalidomide is nonteratogenic in chicken and zebrafish embryos and nonneurotoxic in vitro

“…Both Lenalidomide and Pomalidomide are used to treat multiple myeloma (8)(9)(10). Pomalidomide is particularly effective in patients experiencing relapsed multiple myeloma (13)(14)(15).…”

“…Lenalidomide, a structural analog of Thalidomide licensed for use around the world, is clinically more potently anti-inflammatory than Thalidomide, with potentially fewer side effects (8,9). However, long-term treatment with Lenalidomide can result in peripheral neuropathy (10,11) and, as yet, its teratogenic properties are uncertain, with only limited studies performed to date (12).…”

Multiple myeloma and persistence of drug resistance in the age of novel drugs (Review)

“…bortezomib and carfilzomib) have provided significant improvements in survival and quality of life in MM (95). IMiDs are structural and functional analogs of thalidomide that have potent immunomodulatory properties, anti-myeloma activity and better tolerability profiles (96).…”