Pomalidomide: the new immunomodulatory agent for the treatment of multiple myeloma

Abstract

In this report, we provide a comprehensive review on the preclinical and clinical investigations conducted in development of the next-generation immunomodulatory drug (IMiD) pomalidomide for the treatment of relapsed/refractory multiple myeloma (MM). We consulted PubMed, MEDLINE, ASH, ASCO annual symposium abstracts and http://clinicaltrials.gov/ for the purpose of this literature review. Twenty-six preclinical and 11 clinical studies were examined. These studies delineate the mechanisms of action of pomalidomide and attest to the robust clinical activity in relapsed/refractory MM. MM is the second most common hematological malignancy in the US. Despite availability of several therapeutic agents, MM remains incurable. Thus, the development of new therapies remains a priority. Pomalidomide is the newest member of the IMiDs class of drugs, and in preclinical and clinical investigations, it has demonstrated an improved efficacy and toxicity profile in comparison to its sister compounds, lenalidomide and thalidomide. Importantly, recent clinical studies have demonstrated its activity in relapsed or refractory myeloma, particularly in lenalidomide and bortezomib-refractory patients. Thus, the addition of pomalidomide to the anti-myeloma armamentarium is widely anticipated to have a significant impact on the overall clinical outcome of advanced stage relapsed and refractory MM patients.

Multiple myeloma cells’ capacity to decompose H2O2 determines lenalidomide sensitivity

“…Lenalidomide-mediated inhibition of HRP was not concentration dependent (supplemental Figure 2B) and inhibited H 2 O 2 decomposition in clinically achievable concentrations. Pomalidomide was the most potent inhibitor, consistent with its perceived clinical potency 20 (Figure 2B-C; supplemental Figure 2A). Moreover, we also confirmed that lenalidomide inhibited intracellular H 2 O 2 decomposition in samples from MM patients (CD138 1 ) at a clinically achievable concentration ( Figure 2D).…”

Pomalidomide for multiple myeloma

“…It differs from thalidomide by the presence of an additional amino group at the fourth position on the phthaloyl ring, and from lenalidomide by an additional oxo group on the phthaloyl ring (FIGURE 1) [5]. Pomalidomide has been approved by the FDA in the US as Pomalyst Ò (Celgene Corporation, Summit, NJ, USA) and by the EMA in EU as Imnovid Ò (Celgene Europe Ltd, Uxbridge, UK).…”

Recent Advances in Antimultiple Myeloma Drug Development

“…As a novel IMiD, pomalidomide inhibits the interactions between myeloma cells and bone marrow microenvironment, and decreases the production of TNF-α and other cytokines such as IL-6 [42]. Studies showed that pomalidomide potentiated the inhibitory effects on its target cytokines better than thalidomide, which resulted in improved therapeutic effects [43]. However, pomalidomide can potentially cause severe embryo-fetal toxicity and venous thromboembolism.…”