Immunomodulatory agents in oncology

The immunomodulatory drug class has a broad range of biological effects with applications both within and outside oncology, and the oral bioavailability of these compounds makes them attractive agents. Thalidomide, the parent compound, was introduced into oncology over a decade ago to test many of its interesting pre-clinical features. While activity was notable in multiple myeloma, there were signals of activity in other malignancies. Multiple combinations have been developed and tested both in relapsed and front-line treatment of multiple myeloma. Based on modifications of the original drug, two derivatives, lenalidomide and pomalidomide, were developed and have been tested clinically. Lenalidomide is more potent in vitro than thalidomide and has demonstrated significant activity in multiple myeloma as well as myelodysplastic syndromes. Clinical activity has been noted in other malignancies too suggesting a broader range of activity. Multiple combinations have been tested as well in the relapsed and upfront setting. Pomalidomide demonstrated increase potency as well in vitro and has just begun early phase clinical testing.