Intro to Myeloma

So the first question that we get asked by patients is what is this and what is this disease going to do to me? Multiple myeloma is a disease in your bone marrow. Inside your bone marrow are the cells that make your blood, your red cells, your white cells, and your platelets. In addition, the bone marrow also is right next to your bone and plays a key role in maintaining the strength of the bone.

Since this is a cancer in the bone marrow, the most common problems with myeloma patients get into is when they have crowding out of their normal bone marrow cells with these cancer cells, the green grass, if you will, doesn’t grow and patients are:
1) unable to make red cells and they become anemic,
2) they may not make white cells so that these blood counts drop making them more susceptible to infection, and
3) they may drop their platelet count, and, therefore, are more susceptible to bleeding.

In fact, most commonly it’s anemia that occurs which can make the patient have fatigue and short of breath. In addition, because again the bone marrow is right next to the bone, the myeloma cells do not allow the bones to function normally. The bones resorb- in other words, they lose bone. When this happens, they break down and weaken so that patients experience bone pain and they often have fractures especially of the spine, hip bones and ribs. Now it turns out that these myeloma cancer cells are derived from a type of normal white cell called a plasma cell. Normally, these types of cells make antibody which is a type of protein. Normally, these proteins help fend off infections and that’s a good thing.

In myeloma patients, patients make only one type of protein and don’t make any other types of antibodies. Because they don’t make lot of types of normal antibodies that are necessary to prevent and fight off infections, they are susceptible to infections. Most importantly, these proteins can get into the kidneys and clog them up. Thus, patients can have significant problems with their kidney function and end up in kidney failure. In addition, the kidneys may fail because when the bones fall apart, and the calcium that is lost from the bone gets into the blood and can wreak havoc on kidney function. Overall, the most common problems myeloma patients get into involve loss of marrow function and therefore anemia, bone-related problems, loss of kidney function, and infections.

The first thing patients want to know is what is this disease multiple myeloma and how is it going to affect me. Multiple myeloma is a bone marrow based cancer of the type of white cell called a plasma cell. The job of the plasma cell is to make antibody and what happens in myeloma is unfortunately billions of these cancer cells take over the bone marrow and wreak havoc. And they wreak havoc because the bone marrow is where you make your blood cells, your red cells, white cells and platelets.

When the weeds that are the plasma cells that are malignant take over the bone marrow, the green grass can’t grow and you can’t grow red cells, platelets or white cells. When you don’t make red cells, you become anemic, and you could be tired and short of breath. When you don’t make white cells, you don’t have the ability to fight off infections. When you don’t make platelets, you can bleed. So most commonly, you don’t make red cells and, thus, are anemic. Not so often, you have low white counts and platelets.

Normally healthy plasma cells each make one antibody.  However, in myeloma, the malignant plasma cells are all of one type and so lots of this protein circulates in the blood. Unfortunately, certain types of these circulating antibodies can clog up the kidneys and cause kidney failure. Because the bone marrow resides next to the bone, the myeloma-infested bone marrow often can wreak havoc on the bones. What does that mean? Bone loss, and when you lose bone, you fracture. You can also have bone pain. So patients may present with fractures and bone pain. In addition, patients can have infections sometimes because they don’t make any other antibody than the one type and they also can have low white counts. So myeloma is most often identified because routine laboratories may show either a low red blood cell count, i.e. anemia, or they have a high total protein count from all of the antibody in their blood. In terms of symptoms, back pain or bone pain is often present, and then X-rays are done and the patient is found to have holes in the bones, so-called lytic lesions, or fractures suggestive that suggest they have multiple myeloma.

Other complaints may be fatigue or tiredness from low blood counts or the myeloma itself which can produce substances which make you tired. You may also come in with bone pain or fractures and sometimes kidney failure and the symptoms of that also may be fatigue or nausea, vomiting or your inability to have any urine output, which in that case means it is very severe. So myeloma is a bone marrow-based disease that can cause problems with the bones as well as the kidneys, not just the bone marrow itself.

How does the doctor actually make the diagnosis of myeloma or in fact rule it out? There’s a series of tests and X-rays that are done in order to establish the diagnosis and determine its severity. First, the blood test and urine tests are done to determine whether the patient is anemic or the kidneys are working poorly or well and whether the calcium level may be high. if the bone loss is severe, calcium levels can get very high in the blood. In addition, we measure the amount of protein of that antibody, that monoclonal antibody called m protein in the blood and urine, and that helps establish the diagnosis.

Recently, we have a newer test called a serum free light chain assay that can measure a part of the antibody in the blood. These tests together help establish whether the patient has an abnormal or monoclonal antibody.  Determining the amount helps determine whether it is enough to call it myeloma or its premalignant version which is called monoclonal gammopathy of undetermined significance or MGUS. A bone marrow examination in which a small amount of bone marrow is removed from the lower back or upper hip, the iliac bone in the lower back, determines whether abnormal plasma cells are present and the percentage of them which helps determine whether the patient has MGUS or myeloma.

In addition, further testing is done on the bone marrow to determine whether the abnormal plasma cells show chromosomal or genetic abnormalities which can help tell us determine the relative severity of the disease which can be helpful in making decisions about how much treatment is necessary. And last but not least, X-rays are done to look for those holes in the bone, lytic lesions, that may have resulted from too much bone loss as well as the films may show fractures. Sometimes additional imaging is done through MRIs or PET scans to more precisely identify lesions or whether those holes or lesions in the bones may lead to problems that may require surgical intervention or radiation therapy.

So the next question the myeloma patient has, “Do I need treatment?” Many patients with myeloma need very little treatment as this disease can progress very slowly. While the patient’s myeloma requires no treatment, we are continuing to make many discoveries with new drugs that we can hopefully have in the clinic by the time the patient would need them to treat their myeloma.

One has to be careful not to over treat a disease that unfortunately remains incurable in the vast majority of patients today. So the decision to treat is the first one. It turns out that most individuals with a monoclonal antibody or M-protein in their blood and/or urine don’t have myeloma. They, in fact, have a disorder called MGUS or monoclonal gammopathy of an undetermined significance in which the amount of abnormal protein is smaller. They also don’t have evidence of low blood counts or anemia. They don’t have significant bone disease, high calcium or kidney disease.  Also their bone marrow shows very few plasma cells (< 10%).

Those patients can generally be watched although if they have evidence of bone loss such as osteopenia or osteoporosis, they may require treatment with drugs to strengthen their bone with drugs like bisphosphonates. Next, there is a group of patients who have what we call smoldering myeloma. This group represents about 10 to 15 percent of myeloma patients. They meet the diagnostic criteria for myeloma in that they have more than the 10 percent plasma cells in their bone marrow. They do have myeloma but they don’t have any clinical manifestations of the disease to make it necessary for them to need treatment. They don’t have high calcium in the blood, kidney failure, low red blood cell count or anemia, and they don’t have fractures or lots of holes in their bones, and they don’t feel poorly from what may be the myeloma. In fact, they’re living a pretty normal life. Those patients generally may benefit simply from treatment with bone strengtheners like bisphosphonates and may not require any other therapy. However, most patients with myeloma come in with one of the signs or symptoms that shows that they need treatment. They feel poorly and they may have bone pain associated with a fracture or holes in the bones. They may be weak and be tired. They may have kidney failure and low blood counts that also be making them feel weak and tired. Those patients require treatment. That treatment can take on many variations depending on the patient’s specific type of myeloma as well as their other medical problems and also their work and lifestyle.

So now that the doctors decided that you need treatment for your multiple myeloma, how do they decide what treatment should be given? That specific treatment will be based on several several things. One factor that is very important, of course, are the characteristics of the disease.

For example, is the marrow very involved with a lot of plasma cells resulting in anemia or other low blood counts? Are there cells in the blood that are of the myeloma type? When these plasma cells are in the blood and have gotten outside the bone marrow, so-called plasma cell leukemia, that is a very serious form of myeloma. How involved are the bones? Are there just a few holes in the head, if you will? Are there lots of lesions all over the skeleton? Does the patient have bone pain as well as fractures from the bone loss? What are the genetic abnormalities in the cancer cells? They may suggest this is a poor risk patient that may require more aggressive treatment.

What is the kidney function like? What is your lifestyle and work style? Are you a very active person? Are you running marathons or are you bedridden from the effects of myeloma and were very active just a few months ago? We also want to know what your other medical conditions are. Maybe you already have kidney disease from diabetes or high blood pressure. Maybe you have heart failure. These can impact the choices that the doctor will make to treat your multiple myeloma. For the patient who has been previously treated, you also want to know what have treatments they have received before and how they tolerated it. Did it cause side effects? Did they feel poorly on it? Were they nauseated? Did they have to stay at home because they were so tired from the treatment? Was it lowering their blood counts which caused delays in further treatment? Was it affecting their liver and kidney function?  All of these should be considered in terms of what that doctors decide to treat you with. Treatment choices have become more complicated thanks to the great increase in treatment options available today compared to just a few years ago when the choices were so limited.

So what are the treatment options today for myeloma patients? Well there are so many more options than just a few years ago. The general classes of drugs include: chemotherapy which are the oldest class of drug along with steroids.  More recently, we have the immunomodulatory drugs thalidomide, followed by Revlimid or lenalidomide and now pomalidomide or Pomalyst. We also have available two drugs with similar mechanisms of action these are called proteasome inhibitors. First, we had Velcade or bortezomib starting in the early 2000’s.  More recently, a second drug in this class has become available called carfilzomib or Kyprolis. We also have drugs that are not approved for myeloma but that can be used such as arsenic trioxide.

In addition, there are lots of drugs now in development, including antibodies and other targets that we will talk about in more detail as we address specific drug classes and options. Key points we’ve learned over the last few years is that actually progressing or not being responsive to one drug does not mean that the same drug will not work when combined with another agent that’s demonstrated benefit for myeloma patients. We’ve learned that with the proteasome inhibitors. For example, when Velcade was used and failed to work with a drug like Cytoxan, then the patient may respond when Velcade is combined with other drugs known to be active for myeloma such as Doxil or steroids.  The same is also true with immunomodulatory agents like thalidomide or Revlimid. What we have learned more recently that even drugs in the same class that the patient has failed can produce responses when another drug from the same class is used. For example, Velcade failures with an alkylating agent Cytoxan may respond to another alkylating agent called bendamustine when combined with Velcade.

Even more startling is that patients failing one immunomodulatory agent such as Revlimid in combination may show responses when the same combination is used with another immunomodulatory agent such as Pomalyst or thalidomide. Similarly, we have shown that patients failing the proteasome inhibitor Velcade can often respond to the same combination when Velcade is replaced with another drug in the same class which is carfilzomib. Thus the number of choices for myeloma patients today is so much greater. In the past, it was that patient had class resistance so that patients failing drugs in the same class would be unlikely when it was used in a new combination. Clearly, this is not the case as demonstrated now in many recently completed clinical studies.

Let’s talk about specific drug classes starting with the oldest agents known as chemotherapy. Some specific drug classes are effective in myeloma, including the alkylating agents and anthracyclines. The oldest drugs are the alkylating agents, including melphalan, cyclophosphamide and most recently bendamustine. These drugs are not particularly active alone but when used in combination with some other agents we will describe below are very active.  Partner drugs for alkylating agents include steroids, immunomodulatory agents and the proteasome inhibitors. These drugs when used at lower doses have very few side effects and uncommonly lower blood counts but other than that and occasional nausea are very well tolerated when given for a few days every month. They can be quite effective for a long period of time.

However, only when combined with other agents and classes of drugs used to treat myeloma today do they show reasonable clinical benefits for myeloma patients. The other major chemotherapy class used to treat myeloma today is an anthracycline. The oldest drug was doxorubicin but in the last few years a newer and safer version has been developed called Doxil or Lipodox, which is a chemically modified form of doxorubcin. It’s like having the drug in a fat globule. It can be given very safely and is very active to treat myeloma patients.

When given alone, it is does not have much clinical activity but when combined with steroids and especially proteasome inhibitors such as Velcade or Kyprolis it’s quite active. Also the same is true when these drugs are given with immunomodulatory agents especially Revlimid and more recently Pomalyst. When Doxil or Lipodox are given conventionally once every three weeks they can wreak havoc in terms of causing mucositis so that the inside of the mouth can hurt and blister and red hot hands and feet especially on the palms on the bottoms of your feet. This can be quite troubling for patients. We now know that these side effects can be greatly reduced and pretty much eliminated when we simply give the drug at lower doses more often- twice weekly.

In addition, when these drugs are combined with other agents, including steroids, the proteasome inhibitors, and especially the immunomodulatory agents, they are both quite active and are associated with very little side effects. The other side effect that may occur long term with anthracyclines that we really don’t see anymore is heart failure. However, it is important for patients to they have their heart function checked with heart tests called an echocardiogram or MUGA scan before they initiate this type of treatment.

One of the most active drugs to treat myeloma today is a steroid. These are not the same steroids that Barry Bonds used; these are the steroids that, in fact, are commonly used to calm down inflammation. These are called glucocorticosteroids. They are also known as corticosteroids, drugs such as prednisone, methylprednisolone or Medrol, and dexamethasone or Decadron. These can be given orally or intravenously to treat myeloma patients. We know that the steroids directly can kill the myeloma cells but equally important they can make the soil less hospitable for the myeloma to grow in, if you will.  It’s no longer fertile, it’s barren soil and the myeloma dies and the patient feels better so steroids remain an excellent drug choice for myeloma patients today and also are very easily and effectively combined with all of the other active drugs used to treat myeloma such as chemotherapy agents, proteasome inhibitors and immunomodulatory agents. They are, in fact, among the most active drugs to treat myeloma and they are certainly by far the cheapest. The problem is that their dosing and schedules can have a big impact on their tolerability and even different ones can have marked differences potency and side effects.

Patients may also develop cataracts after long-term use. Some patients don’t like being on steroids. However, it turns out the dose and type of drug and schedule is very important in terms of patient’s ability to stay on these drugs with minimal negative effects. In our own practice, we believe that IV treatment results in fewer side effects, less inability to sleep, so-called insomnia, less hyperactivity, and reduced negative effects on mood. We also think that when given in pill form that methylprednisolone or Medrol seems to be better tolerated particularly when given at lower doses every other day. Studies done recently showed that the amount of steroids that we used up until recently was much too much. These led to poor outcomes for patients because of the many side effects that patients experienced.

Problems when taking the drugs at the higher doses included more infections, blood clots and increased blood sugar. The results of a recent randomized trial showed us that less was, in fact, “more” as patients were able to remain on their treatment resulting in improved outcomes at, in fact, lower doses of steroids. With lower doses and differences in doses (lower), types and routes of administration, patients are able to live happier and more fulfilling lives on these drugs. Even if they are an old drug, steroids really do work especially when used in combination. We have learned that when you combine these drugs with other types of agents, you can use much less effectively without all of the side effects that we used to see before we had the opportunity to combine these drugs with all of the new types of drugs to treat myeloma patients.

Another class of drugs commonly used to treat myeloma today are the proteasome inhibitors. This started with bortezomib or velcade about a decade ago. These drugs in fact make other drugs to treat myeloma much better. We call these drugs chemo sensitizers. They make the other drugs look just that much better like the chemotherapy drugs, like the steroids, we know they as well directly kill mile they also make myeloma cells unable to grow as well They have a multitude of different ways in which they accomplish these goals but basically then inhibit a system in ourselves but the garbage can on the cell and when the garbage can is close toxic proteins accumulate and those proteins allow myeloma to died.

The good news is that myeloma cells are much more sensitive to this impact and other cells in the body. These drugs have been used first to treat late-stage myeloma and today often as front-line treatment for myeloma. Their activity is much better as their combined with steroids with chemotherapy and immunomodulatory agents. Today it is uncommon that they’re used to alone. The drugs can cause side effects, specifically most commonly they can cause neuropathy numbness, tingling, burning pains in hands and feet and sometimes weakness in the legs and the arms. These effects can be reduced if the drugs are given at lower doses on longer cycles and if the drug is given subcutaneously. These three things result and much less than neuropathy and patients staying on drugs and we’ve learned particularly when the drugs are combined these lower doses and longer cycles can be very effective.

The drugs can cause shingles so we recommend that patients be treated but anti-viral drugs like acyclovir or valtrex or vamthere. If they’re treated with Velcade the drugs can also lead to reductions in blood counts so we watch those as well when patients are on this treatment. These are highly effective drugs have certainly improve the quality and the length myeloma patients’ lives today. The newer kid on the block approved about a year ago in 2012 is a drug called carfilzomib or kyprolis. This drug too is quite effective to treat myeloma and in the same class as velcade has similar mechanisms action but can also it turns out overcome resistant to velcade, therefore at to us a great option for patients who failed valcade as well as it turns out other immunomodulatory agents. It causes less neuropathy than velcade and therefore is a good option for patients who have velcade induced neuropathy. Like velcade it is much more effective when combined with steroids chemotherapy or the immunomodulatory agents such as thalidomide, revlimid, or pomalyst.

Another class of drugs that’s quite effective are the immunomodulatory agents. These included first thalidomide more recently revlimid or lenolidomide and just most recently the approval of pomalidomide or pomalyst. These drugs are called immunomodulatory agents because they help boost the immune system and take away the part of the immune system that suppresses the immune functions from killing myeloma. They have a multitude of other ways to kill myeloma. They reduce blood vessels that feed the myeloma. They can kill myeloma directly as well and they again make the neighborhood in which the myeloma cells grow less hospitable for that to happen. Although somewhat active a single agents their activity is greatly boosted when their combined with steroids. They also are very effective when combined with Velcade and carfilzomib as well as other chemotherapeutic agents.

These drugs are not only active a single agents but their activity is greatly boosted when combined with other drugs such as steroids, chemotherapy, or the proteasome inhibitors such as bortezomib, velcade or carfilzomib, kyprolis. The other good news is when their combined I believe that their doses can be reduced and therefore they can have less side effects. The side effects of thalidomide particularly are peripheral neuropathy, numbness, tingling, sometimes burning pain usually irreversibleness drugs can also cause constipation and certainly can  increase the risk of blood clots and the like in Long especially when combined with steroids and some types of chemotherapy.

The drugs are very active and can be given for a long period of time but there seems to be small risk secondary cancers now recognized with revlimid or lenolidomide. Their ability to lengthen lives in myeloma patients for outstrips their lower risk a secondary cancer which is specially seems to be true in patients who had high does therapy and transplant which is certainly not being done is commonly today to treat myeloma patients. Side effects of these drugs may also include tiredness as well as inability to think what is clearly.  But lowering the dose can certainly help overcome that and when these drugs are given in the evening that can help as well.

Now since the drugs are clear in the kidney patients may require a reduction in the dose we know that’s true where for revlimid not so true for thalidomide and probably not pomalyst as well but we have to recognize the drugs certainly can be given safely all of them to patients with poor renal function or kidney function you just have to reduce the dose. In terms of reducing the clot risk, we simply a patient’s take baby aspirin in order to help without problem. Again there’s a very active class of drugs and very active when combined with the other classes such as the chemotherapy, the steroids and the proteasome inhibitors.

So what’s happening in myeloma today in terms of new agents? It’s an explosion today. There are so many new agents in development. The major agents in development that are very exciting are the antibodies and the antibody conjugates. Well we’ve used antibodies to treat other cancers very effectively such as the lymphomas the skin cancer melanoma and chronic leukemias but we haven’t done much in myeloma but there are a pile of new drugs coming on.

Drugs that target markers that are present on the myeloma cells and when these are attacked by the antibodies the myeloma disappears. The most exciting development the last few years is the ability to have the antibody combined with drugs. So why does that help things? Because if we can deliver the drug just to the cancer cell because the antibody binds the cancer cell with the drug and that drug can just get into the cancer cell we can deliver therapy that truly is tumor-specific and get lots of the drug in a the cell and wipe out the cancer cell and leave the rest to the patient alone. And we’re finally doing that in the laboratory and actually curing mice with myeloma for the first time we hope that in the clinic soon. And there are drugs in early development to do that. Some of these drugs are effectively now being used to treat other types similar cancers such as lymphomas.

We also are developing other targets in myeloma, targets for other pathways within the cell that may become effective. These include the PI three kind ace inhibitors as well as the histone deacetylase inhibitors these drugs don’t seem particularly active alone again like the velcades and immunomodulatory agents may make other drugs work better. These are works in progress presently we hope over the next few years we know how to use these so we can attack the myeloma cell and leave the rest of the body alone. That’s our goal now is to get therapy that truly is only tumor-specific.

So how do we know if the treatment is working or not working? Well, we measure not the amount of that tumor cells themselves are the bone marrow you can’t get to them, we measure the product that antibody marker. Does it go up doesn’t or go down we measure that the blood and the year so most patients have it in their blood sometimes about 15 percent of patients only have the protein in the urine it’s just part of the antibody.

We now have this newer assay the serum free light chain so we can do that measurement not only the urine but the blood as well. So when we measure that reduction in protein we call those certain degrees a response. If it’s 25 to 49 percent below where you started it’s a minimal response. Fifty to eighty-nine percent partial response ninety percent but not all gone a very good partial response and if that marker disappears completely we call it a complete response. The urine numbers are done a little differently. At least 50 percent for minimal response ninety percent for partial response these days it’s fairly common for patients to respond to some degree and many patients achieve complete responses. However, the achievement of complete response disappears that protein marker doesn’t mean the patients cure them I’ll it certainly can come back in time.

The good news is today there are so many options so when it comes back when we say, “Okay it’s progressing?” If it goes up by more than 25 percent we say your progressing we also want to know if it’s not be well tolerated are you feeling crummy? Are you tired? Are you having pain? Are you nauseated? That may make us want to change therapy or at least reduce the dose how’s it impacting your blood counts, your kidney function that also made lead to changes in the dose or schedule the drugs as well. So it’s not necessarily all about is the disease getting worse or better but also how you’re feeling on the trip because today there are a lot of other options we didn’t have simply a few years ago that you could try if you’re not tolerating the present therapy well.

So if I’m being treated, how long do I have to stay on the treatment? The data is emerging that maintaining the remission maintenance therapy is a key part of the treatment plan for your myeloma today. Early studies we and others performed first showed that steroids were effective and more recently studies with lenolidomide (revlimid) have shown an improvement in survival with their long-term use although we certainly use the proteasome inhibitors first velcade and now carfilzomib long term and they seem to be very safe.

There’s really not a lot of randomized data that shows they are effective as maintenance agents but we’re doing it we believe that patients need to stay on treatment because this disease  remains incurable today and we want you to stay in remission as long as possible. We also though, use lower doses and we give patients less of those drugs per month. By giving them less often especially drugs which the patient has to come to clinic, like the proteasome inhibitors if they’re given for maintenance. However, that doesn’t have to be true with oral agents such as revlimid and or steroids but maintaining the remission is a key part of the treatment plan. So we do keep the patients on treatment but we give them less drugs per month.

We try to make the schedules more convenient and we certainly want them to maintain their quality of life or it to improve when they move to maintenance treatment. We do take out the chemotherapy agents, the doxils, the cyclophosphamides, the melphalan, the bendamustine; because we know long term these drugs can cause permanent damage on bone marrow and in the long term prevent the patient from receiving these drugs in other combinations.

Anemia

It’s likely that sometime during the course of your myeloma that you’re going to become anemic. So what is anemia? It means your red cell count is low. So what does that do to you if your red cell count is low? Well red cells carry oxygen, so if you don’t have enough oxygen as you know, you’re going to feel weak and tired. So we’re going to do everything we can to prevent that. But, it turns out there may be a lot of reasons why that may be occurring in a myeloma patient. It could be the myeloma itself is making it so you can’t red cells in your bone marrow. After all, the red cells are made there and the myeloma cells are lurking there. They may shut off your ability to make red cells if they crowd out the bone marrow. It could be the treatment, chemotherapy or radiation. It can shut off red cell production. It also may be that your kidneys are working right from your myeloma or other causes and so you’re not making the growth protein we call EPO for red cell production. Without that, you’re going to become anemic as well. So how do we monitor. We simple measure your blood the number of red cells. We call that your hemoglobin, you hematocrit, or your RBC count. If the count is low enough we’re going to want to either transfuse you or we’re going to give you some supplements to help you prevent anemia. The best one we have right now is called EPO erythropoietin. This is in several forms today, either Aranesp or Procrit. And these can boost your hemoglobin level. But we’ve also learned over the last several years many patients with myeloma are iron deficient. An in fact, simply giving EPO isn’t enough. They need iron as well, especially IV iron. Now with lots and lots of transfusions however, if the EPO doesn’t work, you may become iron overloaded and cause you to in fact have problems in your heart, liver, or other major organs. We have drugs to help that called Exjade. Proper monitoring of your hemoglobin is key to the long-term success with your myeloma treatment. Recently there’s concern they use of EPO in patients with myeloma and other cancers that perhaps it’s actually speeding up the cancers growth and shorting the survival of cancer patients. There’s studies looking at this, some have shown that’s true, some have not and for that reason you don’t want to go overboard with the use of drugs like Procrit or Aranesp. Your doctor will work with you to make sure you’re only receiving it when you absolutely need to so we want to make sure that you have proper levels of circulating red cells so you have good energy but we don’t want to overdo it. So make sure your doctors are measuring that hemoglobin level on a regular basis and treating you with either drugs like Procrit or Aranesp or if need be transfusions so you have good energy.

Arsenic Trioxide

Now that you’ve heard about three recently approved new drugs to treat myeloma Revlimid, thalidomide, and Velcade, let’s talk about another relatively new drug that’s approved to treat leukemia APL but not myeloma, arsenic trioxide. This is a heavy metal that showing great efficacy to treat myeloma patients today especially when used in combination. We don’t completely understand how it works but we do know like Velcade it also prevents the breakdown of proteins that cause myeloma cells to die. It also potently inhibits the formation of blood vessels we know this is also important growth myeloma. The drug is administered intravenously it usually takes several hours to give it. It’s given a couple times a week although the schedules very. Now it has a distinctly separate side-effect profile specifically the drug can slow the heart rate and so we monitor the electrocardiogram or EKG periodically in patients who get it. Given weekly at first and then monthly after the first several months. It’s rare that this effect occurs but can be serious. Importantly to reduce that side effect we have to keep the potassium and magnesium levels high that reduces the risk. And rarely much more infrequently than Velcade or Thalidomide this drug can cause numbness or tingly. The drug is active especially when combined with other drugs vitamin C evolve things when you use by them and see with arsenic you’ll or something in the so-called *** and that makes the arsenic work better it’s also effectively use with steroids a variety of chemotherapy agents and more recently thalidomide and Velcade. This drug can be safely administered in the setting of kidney failure and even in patients on dialysis and many times it can reverse kidney failure very important for our myeloma patients who are commonly develop kidney problems. Now that you’ve heard about all the specific drugs to treat myeloma itself over the next few sections were gonna tell you about the specific complications the occur in myeloma patients and how we can deal with them with both treatment with medications as well as surgery.

Bone Disease

Now that we’ve learned about what myeloma generally is and how to treat it let’s talk about the specific clinical manifestations of the disease. The most important of which is bone disease. Patients with myeloma lose bone why because the Pac man cell in the bone call the osteoclast is stimulated to actually get rid a bone by the myeloma cell. So our job is to stop that osteoclast from activating and destroying bone. Fortunately today we have drugs that help with this called bisphosphonates and the monthly infusion of either Zometa or Aredia has been dramatically shown to reduce the risk of fractures and actually cord compression often in the past leading to radiation or surgery to bone. That’s no longer the case is much today because the effective use of these drugs. These drugs are very potent and as a result can have negative impact on the kidney so it’s important that patients have monthly monitoring of the kidney function. As well infrequently patients may have jaw problems resulting often from surgical procedures such as the extraction of teeth. So maintaining dental health is a key to making sure these drugs not only are effective but reduce the risk of jaw problems that can and frequently come from the treatment these drugs over the long term. Not only can we show effectiveness with drugs like bisphosphonates but we also know that simply vitamin D and calcium can help. It’s important that vitamin D levels be measured in all myeloma patients, many of them are vitamin D deficient. So simply the usual amount like 800 units a day or calcium that one gram a day may not be enough that a patient as vitamin D deficient. A frequent problem in myeloma patients you may need more to actually have your vitamin D in the normal range. In addition to medical management in treatment with drugs or vitamins we also may have you seen by an orthopedic surgeon. They can help assess your bone disease, does it need surgical intervention, and does it need the help a physical therapist her rehab doctor. Remember the oncologist and hematologists are trained in bone marrow not in bone that requires the intervention an orthopedic surgeon. We also believe that staying active is very important weight-bearing exercise keeps your bones healthy and happy don’t lie around that’s how we cause more bone loss more fractures so overall keep your bones healthy and happy over the long run requires an integrative approach not only involving treatment with drugs like bisphosphonates or vitamins like vitamin D or minerals like calcium but also the involvement of an orthopedic surgeon often physical therapists and rehab medicine doctors as well. Occasionally patients may work for radiation therapy to relieve bone pain or treat fractures but this is being used less and less these days with the effective use of bisphosphonates in the interventions that are now available through or orthopedic surgical colleagues

Clinical Research

You may be asked to participate in clinical research and you may want to know what clinical research is before you even will decide that you want to participate. This involves the testing of drugs that we hope will help lots and lots of patients, like you, with myeloma. So we do many types of clinical trials to determine whether drugs either are safe or more effective than the presently available agents. The clinical trials are done in stages ranging from stage 1 to 4. In stage one we don’t even know if the drug is safe so we’re just trying to evaluate safety and we hope to get a hint have activity. In stage two trials, now that we know the proper dose that safe and well-tolerated we test them and a lot of patience with your disease and once we establish that they have some good activity to knock out the myeloma, we move them the state’s three in which we randomized patients to either receive  the tried-and-true gold standard compared to the new treatment which we hope is better and finally, in stage four trials now that we know this is better than the gold standard other subtypes that it may work in better or there may be slight twists with the treatment in terms of the regimen or how often we give it or for how long that may make it even better for our patients. There also may be trials that are called PC or PD trials. So what are these? These are Pharmacokinetic or pharmacodynamic trials which test not necessarily whether the drugs work but correlate the drug levels with their effectiveness and also look at other measures of outcome besides just the myeloma. All these help teach us in a way that we can help lots and lots of other patients like yourself. So for you to make a decision about whether you want to participate in trials, you have to decide if the extra effort on your part you may need additional blood draws, you may have to come to clinic more often for those blood draws and other tests that are part of the trial. You have to weigh that against the possible benefit for you if you will helping many other patients like yourself over the long run. Overall with a clinical trials are great thing to participate in because the old treatments from a few years ago you have to remember were the new treatments ten years ago in the new treatments today that we’re using in the clinic are going to be the all treatments a few years from now and all of these have led to not only improvement in the length of your lives with myeloma but just as important the quality as well.

Kidney Disease

Another frequent problem with your myeloma involves the kidney. Your kidneys may be negatively impacted directly by the myeloma cells, by the antibody produced by the cells or breakdown products called amyloid. Also very commonly patients may have high calcium from the release of calcium out of that bone. All these may lead to kidney disease, but also there may be drugs are receiving for the myeloma. Drugs like the bisphosphonates, antibiotics, or other treatments for the myeloma. Frequently myeloma patients may have other diseases that cause kidney problems like diabetes or hypertension so it’s important to make sure those are in control so we’re not negatively impacting your kidney even more than simply from the myeloma itself. Now to reduce the impact of kidney disease, it’s important that you see a kidney specialist if you have a very abnormal kidney function. They help a lot with management your fluids, your phosphate levels, and other minerals that may be impacted by kidney function we don’t want you to end up on dialysis. Another important point is that you keep yourself well hydrated. Lots of fluid is a key and minimizing dehydration will reduce your risk ever having a kidney problem. So overall kidney disease is commonplace reducing its risk involves effective treatment the myeloma making sure you’re receiving proper doses of drugs if your kidney function is not normal because in fact you may have to reduce the dose is a many drugs and also making sure the drugs you’re receiving are not ones that put you at additional risk for kidney problems.

Nerve Problems

Nervous system problems are commonly seen in your myeloma. They may involve the central nervous system from drugs we use, drugs like thalidomide that may make you sleepy the central nervous system means your brain. More frequently these problems involve your peripheral nervous system that is the nerves that innervate your hands, your feet, your arms, and your legs. Often patients develop peripheral neuropathies; numbness, tingling, and less often pain in their hands and feet. This may be from the antibodies themselves that can coat the nerves and make them not work right. But more frequently today that’s from the medications we use drugs like velcade and thalidomide which often cause nerve damage resulting in the peripheral neuropathy. Now the treatment of this may involve drugs such as Neurontin or the more recently developed drug Lyrica. Other drugs used involve Cymbalta and doxepin. In addition, over-the-counter medications may help. We often use alpha lipoic acid. This helps to reduce the risk neuropathy and among patients who receive thalidomide or if you’re also on Velcade we keep them on this as long as our on these drugs to reduce the severity and the risk of neuropathy. Now in addition to the drug induced nephropathy we also note that infections can cause nerve problems. Infections like shingles or herpes zoster. This is the reactivation and the chicken pox virus and we give patients who receive drugs like arsenic or Velcade long-term acyclovir or other drugs that are antiherpetic this is a herpes virus the one that causes shingles so if we give an antiherpetic drug we’re going to reduce the chances of you getting shingles. So it’s very important to let your doctor know if you’re experiencing any problems with your nerves especially if you’re on drugs that may be causing it because they want they want to intervene with drugs they may want to reduce the dose is the drugs are receiving or stop them all together. So communication is the key which will lead to long-term benefits from the drugs you’re receiving for myeloma without and toward side effects that may not be reversible if they’re not either discontinued or reduced in dosage soon enough.