All about Darzalex, Daratumumab and Darzalex Faspro. Hi, my name is Don Benson. I'm a professor of medicine at The Ohio State University with our multiple myeloma program here. I'm very grateful to be part of the series talking about monoclonal antibodies. 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. Monoclonal 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. 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, Faspro, is much more convenient and much more practical for patients. How does it work? Monoclonal antibodies, sometimes called naked antibodies, are made in a laboratory. These man-made antibodies are designed to function like the naturally occurring antibodies in our immune system. They target specific proteins called antigens on the surface of cells. Monoclonal antibodies attach to the target antigen and can restore, enhance, or mimic the immune system's attack on foreign cells. 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 Darzalex, 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. Darzalex also can kill myeloma cells directly through a process called apoptosis, which means programmed cell death. And finally, Darzalex can also work through a third complementary pathway called the complement pathway to kill myeloma cells. When are Darzalex, were Darzalex Faspro used? Darzalex has several indications. It's given in a regimen for newly diagnosed patients in combination with Revlimid or lenalidomide and dexamethasone. It can also be given in newly diagnosed patients with melphalan and prednisone and bortezomib 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 stent. Although that's not commonly used in the United States. Other indications for Darzalex in the NCCM guidelines for newly diagnosed myeloma include Darzalex with Revlimid, Velcade and dexamethasone and Darzalex with Cytokin, Velcade and dexamethasone. On July 30, 2024, the U.S. Food and Drug Administration approved Darzalex Faspro in combination with Velcade, Revlimid and dexamethasone for induction and consolidation in patients with newly diagnosed multiple myeloma who are eligible for an autologous stem cell transplant. Patients will have the opportunity to receive this Darzalex Faspro based quadriplet therapy and initial diagnosis, providing them with a new treatment that may significantly improve outcomes. 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. Darzalex has many specific indications in relapsed and refractory myeloma. According to the NCCM treatment guidelines for myeloma, Darzalex can be used in the following combinations. The preferred combinations are Darzalex with Revlimid and dex, Darzalex with Velcade and dex, and Darzalex with Kyprolis and dex. Other combinations are Darzalex with Cytokin, Velcade and dex, and Darzalex with pomelist and dex. Darzalex may be useful in certain circumstances by itself or with cellynexer. What are the common side effects associated with Darzalex and Darzalex Faspro? Darzalex 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. To reduce the risk of delayed infusion reactions, post-infusion medication should be administered the day after every infusion, and oral corticosteroid which is fewer than 20 milligrams of methyl per nisalone or an equivalent is administered. However, if a background regimen specific corticosteroid like dexamethasone or prednisone is administered the day after two hours of infusions, additional post-infusion medications may not be needed. The most common side effects of Darzalex or Darzalex Pro include tiredness, nausea, diarrhea, shortness of breath, feeling weak, fever, cough, cold-like symptoms or an upper respiratory infection, nerve damage causing tingling, numbness or pain, swollen hands, ankles or feet, and constipation. Tell your health care provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of Darzalex or Darzalex Faspro. Call your doctor for medical advice about side effects. Darzalex or Darzalex Faspro can decrease white blood cell counts which help fight infections, and blood cells called platelets which help clot blood. Your health care provider will check your blood cell counts during treatment with Darzalex. Tell your health care provider if you develop fever or have signs of bruising or bleeding. Additionally, suggestions for managing fatigue and other side effects discussed in this video can be found in the Side Effect Solution Tool of Health Tree Cure Hub. Search on a specific side effect to find solutions that others have found helpful. These solutions have been provided by patients just like you. You can also search side effects by an individual drug or combination of drugs. When searching a combination of drugs, keep in mind it might not always be clear which drug is creating which side effects. What pre-infusions are administered? 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 Darzalex. Personally, that's one of the advantages I like with the drug to give somebody remission that doesn't involve chronic steroid use. What pre-infusion medications are needed with Darzalex Faspro? With Darzalex Faspro, which again is that subcutaneous shot version of the drug, we still use the same pre-medications that we do with the IV dose. Again, it's the same drug, it's the same chemistry and the same pharmacy, and so we will typically pre-medicate again with the corticosteroid, with dexamethasone, 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. Janssen, the makers of Darzalex, recommend to also use acetaminphins such as Tylenol as a free medication. What is the dosing schedule of Darzalex and Darzalex Faspro? It's typically given, it depends on the combination and 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. Darzalex and Darzalex Faspro have the same schedule. The schedule depends on what combination of antimyloma agents you are prescribed and whether you are newly diagnosed or relapsed. Below are the typical schedules that are recommended, found on Janssen's website. Janssen is the maker of Darzalex and Darzalex Faspro. The following combinations were tested with Darzalex in clinical trials. Each combination of Darzalex and other drugs that has been tested in clinical trials has its own dosing and scheduling. You can find these schedules at Darzalex.com. How long is the Darzalex infusion? 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 eight, nine, even ten 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 prospective study with what's called rapid infusion. And 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. One of the advantages of the FastPro formulation, though, is that it's very easy to do 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 capillite 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 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. It takes a long time to get the blood type in that one dose. It is important to note that Darzalex and Darzalex FASPRO binds to red blood cells and interfere with blood bank compatibility tests, including the antibody screening and cross matching that are a part of routine pre-transfusion workups. It is important that you get your blood types prior to starting Darzalex, and you can do that through the dosing interval. a part of routine pre-transfusion workups. It is important that you get your blood types prior to starting Darzalex and to let all your doctors know that you are receiving Darzalex and that it may interfere with your blood type matching. Janssen provides support to patients and caregivers through their CarePath program. Janssen CarePath will help you find the resources you may need to get started and stay on track. CarePath will give you information on your insurance coverage, potential out-of-pocket costs and treatment support, as well as identify options that may help make your treatment more affordable. Call the Janssen CareerPath Care Coordinator today at 1-8-4-4-5-5-DARA Monday through Friday from 8am to 8pm Eastern. Create a JanssenCarePath account at myjanssencarepath.com or visit janssencarepath.com slash darzalex slash fastbro.