[Music] i'd like to talk a little bit about a drug called implicit or elo2mab this is a member of a family of treatments for myeloma called monoclonal antibodies monoclonal antibodies have been around for a long time and there's dozens of monoclonal antibodies used to treat all kinds of medical conditions not just cancer but for over 20 years we've used this class of drugs in medicine elotuzumab or implicitly was the second monoclonal antibody fda approved for myeloma in the united states back in 2015. elotuzumab works as an immunotherapy or immune therapy and when given it enters the bloodstream and attaches to the myeloma cells on a protein called slam f7 if you're doing your own research if you're on the internet and looking up some of the older papers will refer to that protein as cs1 although it's the same protein as slam f7 which is the preferred name in contemporary times when elotuzumab attaches to that protein on the myeloma cells it serves as a flag to recruit the body's immune cells to come and kill that cancer cell kill that myeloma cell elotuzumab also has an interesting second mechanism of action in that there are types of immune cells that combine two to actually stimulate their activity and augment their ability to kill myeloma cells elotuzumab is a v or implicit elotuzumab implicitly is a very well tolerated drug it's given intravenously and currently has two fda approvals one is in combination with revlimid and dexamethasone and the other is in combination with pomelus and dexamethasone in both instances the drug is typically given on a weekly basis for the first two cycles and then goes to a bilique infusion after that it is an immune therapy which means most of the side effects mainly have to do with immune type reactions such as allergies especially with the infusion and with most of these drugs that risk is the highest the first day the patient receives the drug we typically give the patient some medications to prevent those kind of side effects such as dexamethasone or benadryl most people do very well with elotuzumab though from a side effect profile implicitly is given in in either two combinations one with revlimid and dexamethasone or with pomelus indexamethasone in both regimens it starts as a weekly infusion through the first two cycles of treatment so for the first eight weeks or so it's given on a weekly basis after that it goes to every other week with either revlimid and dexamethasone or pommalist and dexamethasone the elotuzumab or implicit infusions are actually a little bit quicker than with other monoclonal antibodies typically these can be given over 30 minutes or an hour and after a patient has had a few doses we can even get it down to a shorter time period than that with implicitly the dose is typically given at 10 milligrams per kilogram so it's a dose based on body weight when it's given with revlimid that dose stays the same when it's given with pomelos it starts at 10 milligrams per kilogram but when it gets into that every other week dosing the dose actually goes up a little bit to 20 milligrams per kilogram so like many monoclonal antibodies that are fda approved and in development to treat multiple myeloma elotuzumab attaches directly to the myeloma cells in fact a little bit of trivia if you look at the generic name for these drugs if there's a t the letter t in the middle of them that means tumor so for instance dara tumumab elotuzumab isotoxumab that t in there is a hint that those drugs actually bind directly to the tumor cells or myeloma cells elotuzumab is an interesting antibody though because it also binds directly to an immune cell called natural killer cells these are a type of lymphocyte again a part of the body's immune system that have the ability to recognize and kill cancer cells without having to go through an educational process like other immune cells in the body natural killer cells when they identify a cell as cancerous can immediately kill that cell and work from my lab as well as others showed elotuzumab seems to have a second mechanism of action where it can stimulate those natural killer cells to augment their ability to kill myeloma cells with implicit or elotuzumab the fda approvals are to give the drug in a combination either with revlimid in a first relapse setting for instance or with pomelos and dexamethasone in a subsequent or later relapse implicity has been studied as a single agent which means given by itself with no other drugs in the combination however its efficacy seems to be a little bit less successful in that setting but is much improved when it's given in a combination yeah it's a little con well it's not controversial but it's it's an interesting phenomenon that um when elotuzumab was in development the the curve certainly separated so in in these trials people took revdex versus revdexilo or palmdex versus palmdexilo and there was a separation you know the response rates were higher and the pfs was better and there was a suggestion in some of these studies that um there was a long tail of durability in in the elotuzumab arm now i think that um i i think that i've seen that with other antibodies too that it's not unique necessarily to elotuzumab but i think the again it's not a controversy but i think one of the interpretations is this idea that if somebody if somebody's going to do well they're going to do well and it may not be necessarily something to do with the drug as much as the subtype of their myeloma or the relationship of the expression of that target to the drug when it's given for instance but that has been brought up before that you see try to do this backwards so it you see kind of this natural decay in the progression free survival curve over time as as people start to have disease relapses and then it gets to this point where it plateaus and levels out and i have those i take care of patients like that who've been on darzalex for five or six years now and are are still in remission and doing great so um francesca cottini is a postdoc in my lab who's actually studying um that phenomenon and and how whether that's immune mediated whether it's related to the type of myeloma that they have um although it's not entirely clear it's um it's something we see in younger patients and older patients it's something that we see in different molecular subtypes so we haven't really seen a predictive signature for that kind of successful obviously we love it when we see it and we wish we could get that in all of our patients but hopefully with her work with francesca's work we'll get to a point where we can predict that a priori and help to personalize a treatment match a patient to an antibody based on some feature that'll lead to that kind of plateau that kind of tail [Music]