What is Dinosomab or Xtiva? So Dinosomab is a bone targeting agent. It's an antibody that targets something called rank ligand. What it does is it activates another cell called osteoclasts in the bone marrow and in the bone. And these osteoclasts destroy the bone. And so what Dinosomab or Xtiva, it's also called Xtiva, what it does is it inhibits this from the osteoclasts by activating rank ligand, which is a protein important for osteoclasts. Prolia the same as Xtiva. Also Prolia is another name for Dinosomab, but it's called Prolia when it's used for osteoporosis in patients that usually don't have multiple myeloma, whereas we call it when it's used for patients with multiple myeloma. What is the indication for using Xtiva? It used to be that patients that didn't have lesions in the bones or bone fractures may not be given bone targeting agents in the past. But then there have been studies specifically in multiple myeloma patients where all patients have received bone targeting agents. And since then, the most standard thing to do is to give bone targeting agents such as Dinosomab to all patients that are newly diagnosed with multiple myeloma because we have a large study that showed that in all the patients, no matter whether they had lytic lesions or not, that it improved, you know, that it basically decreased what we call a skeletal related event. So it decreased the risk of fractures in myeloma basically. So it's in all patients. How do you choose between using Xtiva versus a bisphosphonate, Zometa, or Radia? So both Xoledronic acid or Zometa and Dinosomab or Xtiva are appropriate to give to patients with multiple myeloma. We at times prefer to use Dinosomab in patients that have kidney failure because Dinosomab is not metabolized through the kidneys, whereas Xoledronic acid or Zometa is. And so it seems to be maybe a safer agent in patients that have kidney dysfunction. How do Xtiva versus bisphosphonates work? The bisphosphonates like Xoledronic acid or pamidrinate work differently than Dinosomab. Dinosomab is a newer generation agent. It's what we call a monoclonal antibody. So it's a protein. And what it does, it attaches to another protein. This other protein is called rank ligand. And what rank ligand does is that it's a very important protein for osteoclasts. And osteoclasts destroy the myeloma bone. So when you take away rank ligand, the osteoclasts die and then the bone is not destroyed. What is a bone remodeling process? So bones are constantly turning over. And that's a very important feature of normal bone, what we call metabolism. And so we have two types of cells that work in harmony. And those are the osteoclasts and osteoblasts. And depending on what signals they receive from the bone environment, they're going to activate one or the other. And so what happens with age is that we have more osteoclasts that actually destroy a little bit the bone than osteoblasts. And in myeloma, it's the same thing. Actually the myeloma itself can produce substances that can stimulate osteoclasts. So it's very important to consider bone targeting agents in myeloma. Do the osteoblasts still work building up the bone? Yes, the osteoblasts work better because the osteoclasts are not there. And there's usually a balance between osteoblasts, which are the cells that build up the bone, and the osteoclasts, which are the ones that destroy the bone. And so when you imbalance that, then osteoblasts work better, yes. Does Ixtiva have any anti-myeloma effect? It is well known that myeloma is not just the cell, but also the cells that are around it that are very important. And so what we have found out is that when we treat the cells that are around the myeloma, in this case the osteoclasts, by affecting Wranglygon, for example, with Denosumab, what we see is that these patients may actually even do better than if they were not receiving any treatment at all. There was a big study comparing Zoledronic acid to Denosumab. And in that study, even though it wasn't the primary endpoint of the study, the patients that received Denosumab, especially a subtype of patients, were more likely to live longer and progress less. So these patients actually had a 10-month, there was a 10-month difference in what we call progression free survival, which is progression of the myeloma or death, compared to patients that receive Zoledronic acid. So it may help. And I think that it probably does help to avoid the myeloma also, the bone targeting agents. Is Ixtiva, Denosumab, an anti-myeloma therapy? Denosumab is not a myeloma targeting therapy, but it targets some of the cells that are very important also to treat the myeloma. So it is very possible that it also helps to combat myeloma, but it is not targeting the myeloma specifically, but it's targeting the cells and the microenvironment in the myeloma. What is the schedule for taking Ixtiva? For Denosumab, the schedule is usually one injection once a month, and people usually give that for about a couple of years, and then it's very important not to discontinue it after that and give at least maybe once a year or once every six months, still an injection because we've observed that in patients that we stop Denosumab abruptly after we the patients have been on it, that the density of the bone decreases substantially after that. So you have to kind of stay for a long time to avoid that basically, that effect where you lose bone density after you've been on it. How is Ixtiva administered and what should patients know before taking Ixtiva? So Denosumab is an injection and it's administered usually in the abdomen, usually how you would administer other medications in myeloma such as bortezomib or Velcade or veratumumab, Darzalex that are administered in a similar way. You can have Denosumab on the same day as your myeloma treatment. The common side effects of Denosumab are bony aches. Bony aches can be treated with Tylenol pre-medication. You could also have decreased calcium in the blood after it's administered, especially if you are one of those patients that doesn't have normal kidney function and then you receive Denosumab, you are at an increased risk for having low calcium in the blood that's usually very easily treated just with calcium supplementation which you should be taking anyway with vitamin D which actually builds up your bones. So it's very important to take calcium and vitamin D when you're taking bone targeting agents as well. Additionally, for multiple myeloma patients receiving extiva, the most common adverse reactions were diarrhea, nausea, anemia, thrombocytopenia, peripheral edema, hypocalcemia, upper respiratory tract infection, rash, and headaches. The most common serious adverse reaction was pneumonia. What is ONJ and is it also a side effect? So one of the most severe side effects that you can have if you're a bone targeting agent, either Zometa or Denosumab extiva, is the osteonecrosis of the jaw. And that's basically that the turnover of the bone gets affected and then you can have areas in your mouth, especially around your teeth where there's a bone that is exposed. That can happen without you doing anything in particular to your teeth. It often happens after you've had like a tooth extracted or you've had some procedures done in your teeth or something. So it's very important to always hold treatment for bone targeting agents before you're going to have some procedures done in the mouth, most specifically tooth extractions. So you know, you're going to have a tooth extracted, you really should be off of Denosumab for a while before that can be done safely. Can extiva be restarted after the dental procedure? You can start it afterwards. Usually once the wound is healed from the extraction, you could probably start it up again, but that would be at least, I would say two to three months afterwards. What is the risk of ONJ? It's not very high risk, but the risk increases with you taking more of the medication. So the more medication you take, the risk is higher, but it's usually less than 5% of patients. How long will a patient have to take extiva? Usually you're on it for life because we don't stop it. You at least take one injection every six months or one injection a year just to prevent this rapid bone loss that we can see if you come off of it. How long will someone take the monthly dose of extiva? It depends, but usually we do about a couple of years. In case of relapse, will patients return to the monthly dose of extiva? Usually we go back to the monthly dose. Should all patients be taking calcium and vitamin D supplements while taking extiva? Calcium and vitamin D should be taken by most patients to help build up the bones together with the bone targeting agents. How does a doctor decide whether to prescribe Zometa, a bisphosphonate, or extiva? I think it may be a preference, but since we have a very large study, which is more than a thousand patients comparing the Nosomab to Zometa. And in that study, there was a difference in progression pre-survival that favored extiva. Even though it wasn't the primary endpoint of the study, I feel a lot of myeloma physicians are giving more Nosomab, but it is not wrong to give either or. If you are an eligible commercially insured patient, Amgen First Step can help cover your out-of-pocket prescription costs, including deductible, coinsurance, and copayment. There is a $0 out-of-pocket for first dose or cycle, and a $5 out-of-pocket for subsequent doses or cycles, up to the brand program maximum benefit. There is no income eligibility requirement.