All About Darzalex (daratumumab)

[Music] hi my name is don benson i'm a professor of medicine at the ohio state university with our multiple myeloma program here and very grateful to be part of the series talking about monoclonal antibodies and first of all a drug called daratumumab or darzalex this was the first monoclonal antibody that was approved back in 2015 to treat patients with multiple myeloma monoclinal antibodies are a big family of treatments for all kinds of conditions not even just limited to cancer there's monoclonal antibodies to treat a variety of conditions and they've been around for over 20 years now in 2015 darzalex was the first one that was fda approved and i'd like to talk a little bit about how this drug works how we use it in the clinic the advantages of this drug some of the risks and side effects with darzalex treatment so darzalex is a monoclonal antibody it's designed to target a protein on myeloma cells called cd38 and darzalx when it's administered circulates in the bloodstream identifies myeloma cells and sticks to them on this protein on the surface called cd38 and when that happens it allows several consequences the first is that it can act as a flag to recruit immune cells to come and kill those myeloma cells darzolex also can kill myeloma cells directly through a process called apoptosis which means programmed cell death and finally darzolex can also work through a third complementary pathway called the complement pathway to kill myeloma cells darzalex has several indications it's given in a regimen for newly diagnosed patients in combination with revlimid or lenolitamide and dexamethasone it can also be given in newly diagnosed patients with melphilin and prednisone and bortezumib or velcade there's another indication that's for newly diagnosed patients where we give the drug with bortezomib or velcade and thalidomide actually if somebody is eligible for a stem cell transplant although that's not commonly used in the united states darzalex is also approved in the united states to treat people whose myeloma has relapsed or come back and we typically use it in combination with revlimid or with velcade and sometimes with a drug called pomelist as well darzolex generally is a very well tolerated drug it's an immunotherapy in other words it's not a chemotherapy not a cytotoxic chemotherapy that works by poisoning the cells but again an immunotherapy which means it works through the body's immune system the main side effect that we see with darzalex is when people get the drug the first time they can have an allergic reaction again because of how the drug works through the body's immune system many people on the first day will experience some subtle and some mild immune mediated side effects such as some hives or some itching sometimes people can have flushing sometimes people can get wheezing or other types of immune side effects and very rarely some people can have anaphylaxis like you hear about people who may have with a bee sting or other allergies we can manage those very effectively in the clinic we can turn the rate of the medicine down we can give medicines to prevent immune side effects and usually people get through that first day okay the interesting thing about darzalex is that generally speaking it gets more and more tolerable as the treatments go by it's typically given it depends on the combination in the setting but typically given once a week for the first eight weeks and then goes to an every other week schedule and finally to a monthly schedule and again it depends on the setting and the combination that you're using i want to just quickly mention since we're talking about darzalex a new treatment called darzalex fast pro that was recently approved in the united states it's the exact same drug as darzalex but rather than given as an intravenous drug it's actually given subcutaneously like a shot they work the same way they're the same drug they have the same efficacy and generally the same risks and side effects although the shot form fast pro is much more convenient and much more practical for patients when we give darzalex we're very careful on the first dose because of the risk of immune mediated side effects and allergy so that first day can be a long day it could be an 8 9 even 10 hour infusion and it really depends on the tolerability and how the day goes there are some hospitals and some community settings where people even spend the night in the hospital and they divide the dose over two infusions again really just for safety purposes once that first dose is done and people tolerate it we can speed up the infusion over time and so the second one may last six hours for instance and oftentimes we can get people down to a four hour infusion which is still a pretty long day if you think about it a couple years ago my colleagues and i here at ohio state did a did a prospective study with what's called rapid infusion and we did we did a clinical trial where we gave patients darzalex over 90 minutes and so these are people who had had at least three doses and tolerated the drug well and published this paper several years ago showing that the 90 minute infusion is very safe actually so in our experience here we typically start slowly make sure everything's well tolerated and then for most of our patients here we can speed the infusion up to the 90 minute infusion this is one of the advantages of the fast pro formulation though because the shot is generally given over 10 to 15 minutes and people can get in and get out and get on with their day with less time spent in the infusion clinic one of the idiosyncrasies of darzalex that's important especially if you have a myeloma that secretes an igg protein is that darzalex itself is an igg antibody and so it can interfere with some of the blood test results when they do the immunofixation or the serum m spike or serum m protein value oftentimes the darzalex in the bloodstream can be captured in that test and falsely raise the result so typically what we do at our center is not only check the immunofixation but check the total igg value and the free kappa light chain value at the same time to get a better context to characterize how well the drug is working there are strategies out there that can subtract out the darzalex part of the monoclonal protein and sometimes we do that in clinical trials and research settings it's not something that's really caught on to my knowledge in the standard of care setting but something just to be aware of that when you start on darzalex it may be working extraordinarily well and you'll still notice a little bit of that igg protein in the blood that's probably the darzalex in circulation so because darzalex is an immunotherapy and there's a risk of immune-mediated reactions and allergy when we give the drug we often pre-medicate patients with drugs to prevent those kind of severe side effects we typically do this with dexamethasone with the steroid that i'm sure everyone is familiar with we also use benadryl and sometimes we use a drug called singulair as well which is an asthma drug that can help prevent those kind of side effects again if they happen they're more common with the first dose and early in treatment and many of our patients once they've been on the drug for a while and their myeloma is in remission and things are under control we can reduce the doses of the dexamethasone and in some cases even get rid of it when we get out to that monthly dosing with darzalx personally that's one of the advantages i like with the drug to give somebody remission that doesn't involve chronic steroid use with darzalex fast pro which again is that subcutaneous shot version of the drug we still use the same premedications that we do with the iv dose again it's the same drug it's the same chemistry in the same pharmacy and so we will typically pre-medicate again with the corticosteroid with examethasone as well as with benadryl and sometimes even with the drug singulair to prevent those kind of allergic reactions and make the drug more tolerable so the dose of darzalex is standardized it's 16 milligrams per kilogram so it's based on your body weight and it's consistent through the dosing interval as long as somebody's on the dose they get the same dose sometimes patients ask me can i do a dose reduction if they've had side effects and typically we keep that same dose at 16 milligrams per kilogram although sometimes we will intentionally space the infusions out to try to help mitigate side effects and improve the practicality and tolerability of the medicine