[Music] i'd like to talk a little bit about a drug called sarclesa or isotoxumab this is a member of the monoclonal antibody family and this is a family of medicines that comprise what's called immunotherapy or immune therapy for myeloma sarkles is the latest member of this family of drugs to treat multiple myeloma just having been approved a few months ago in 2020 and its fda approval is to be given with pomelist and dexamethasone in the relapse setting after someone's already had a couple treatments for myeloma sarclessa is a monoclonal antibody treatment that's given intravenously through the vein and the way it works is it gets into the blood system and recognizes myeloma cells and sticks to a protein on their surface called cd38 this works a little bit like darzalex or daratumumab in that they recognize the same target this protein called cd38 on the myeloma cells when sarca binds there it acts as a flag or a beacon for the immune system to come and kill those myeloma cells and it's especially potent when it's given with a drug called pomelos and dexamethasone we did some of the early studies here with sarclesa and happy to see that it's approved now and available for our patients sarclesa is given on a weekly basis to start over the first four weeks and then like other monoclonal antibodies its administration becomes a little bit less frequent it goes to every other week like most of these drugs in this class the main side effect that we watch out for with sarclessa is that people can have immune mediated reactions or allergic reactions during the infusion while they get the drug these can be things like hives itching rash sometimes people will get wheezing they'll feel flushed or hot rarely people can have anaphylaxis like you hear people having to a bee sting and we actually use an epipen in those setting that's very rare but can happen the side effects are mitigated or reduced by giving pre-medications for the drug such as dexamethasone or corticosteroid benadryl as well to help tamp down that potential for an immune reaction and make the drug more tolerable as we give it with sarklesa the infusion rate generally is mediated by how well the drug is being tolerated we can typically give it over an hour or even less once people have become accustomed to receiving the drug so currently sarkeesa only has one fda approval which is in a combination with pomelos and dexamethasone sarclesa is given it a dose of 10 milligrams per kilogram so it's based on your body weight given once weekly in the first four weeks and then goes to every other week after that yeah so generally with sarclessa the first infusion is not a long it's not as long as a first infusion with darzalex for instance those infusions with darzalex which is another monoclonal antibody in this class the first infusion can last eight nine ten hours and and sometimes even over the course of two days with sarclessa the first infusion may take an hour or two but generally we can get the drug administered safely without those prolonged infusions like we see with the intravenous form of darzalex so darzalex is a monoclonal antibody that targets cd38 and sarclessa is also a monoclonal antibody that targets cd38 they both target the same protein on the myeloma cells although they have subtle differences in how they work and their mechanisms of action darzalx has been fda approved since 2015 and we use it very commonly in a number of settings in the newly diagnosed setting in the first relapse darzalex has a number of indications currently sarclisa which was just approved a few months ago in 2020 only has one fda approval so far and that's with pomelos index methazone in the relapse setting so one of the questions that often comes up is can sarclesa be effective if somebody's already been treated with darzalex and the answer is we don't know the answer is it depends anecdotally i've had patients who have received sarklesa and had a response to that treatment after having been treated with darzalex previously but i've intentionally done that in the care of patients where we can separate those administrations by several years as long as possible we don't really know exactly why darzalex stops working it seems to be more complicated than just simply losing cd38 on the surface of the myeloma cells or down regulating that protein it's a complicated reason why and how darzalex loses its effectiveness and my my sense is that the utility and the efficacy of sarcasm may depend on how the response was lost to darzalex now there are some patients who are on darzalexan in remission and stop the treatment for one reason or another and those patients may respond readily to sarclesa in the future but again i think we need to learn more about why these antibodies stop working before we can figure out how to implement them optimally in a patient's care over a series of treatments over a course of time