[Music] what are immunomodulatory drugs and how do they work so imids uh of course have a a slightly controversial history prior to the discovery that they were effective in myeloma thalidomide was as a lot of people know initially used for morning sickness in uh pregnant women and obviously that had a terrible pteradogenic or birth defect effect i was later actually realized that this compound could have a beneficial effect in myeloma and it was tested in that arena and had some efficacy the phallidamide also has some nerve toxicity and causes somnolence so it's next generation agents lenolidomide and pommalidomide have less of these neurologic side effects and are very effective and better tolerated as well as a class of drugs these drugs target both the myeloma cell and also immune cells and what they do is they they actually lead to the degradation of uh specific proteins they're called icaros proteins and those proteins that are degraded actually uh affect different processes in the myeloma cells that leads to the death of the myeloma cells and then then in the immune cells in the immune cells they actually lead to further activation of immune cells um and so in that sense that's why they are called immunomodulatory drugs because they have this multiple um immune effects where they lead to activation of uh natural killer cells and t cells uh that are thought to be important and part of the efficacy of these drugs so one form of immunotherapy that probably everybody is familiar with in very broad terms is our drugs such as uh revlimid and pomelinamide these are developed as what are called immunomodulatory derivatives of a drug known as thalidomide which was a very old drug and what it does is that it globally improves the patient's immune system in addition to fighting the myeloma so it probably has several roles and that has really served as a baseline for a lot of other therapies that have been developed in large part because it can continue to modulate and potentially enhance immune responses you