Background: Multiple myeloma (MM) is a hematological cancer caused by a proliferation
of clonal plasma cells, leading to anemia, renal failure, hypercalcemia and destructive bone lesions
resulting in significant morbidity. The overall survival has significantly improved with the incorporation
of immunomodulatory drugs (IMiDs) and proteasome inhibitors (PI).
Objective: Here we provide a comprehensive review on IMiDs including molecular mechanisms,
recent advances in therapeutic applications and management of toxicities in the treatment of MM.
Methods: Relevant publications in peer reviewed journals were retrieved by a selective search of
PubMed. Systemic reviews, meta-analyses, randomized controlled trials, and treatment recommendations
were reviewed and are summarized here.
Results: Thalidomide, a first generation IMiD, is associated with significant toxicity in older patients.
Lenalidomide, a more potent second generation IMiD with fewer side effects than thalidomide,
is commonly used in newly-diagnosed multiple myeloma, relapsed refractory myeloma and as
maintenance therapy after autologous stem cell transplantation (ASCT). Pomalidomide, a third generation
IMiD, is 10 times more potent than lenalidomide and has shown impressive results in relapsed
MM patients and in those refractory to both lenalidomide and bortezomib.
Conclusion: The clinical use of IMiDs in MM has significantly improved long-term survival and
quality of life. Future studies are looking into novel biomarkers predictive of outcome in MM and
new combinations of lenalidomide and pomalidomde with PI, monoclonal antibodies, immune
checkpoint blockers and several other chemotherapies.