Myeloma

Another class of drugs that is highly effective for treating myeloma are the immunomodulatory agents. These are administered as pills. First, thalidomide was used 20 years ago and more recently lenalidomide or Revlimid and then finally pomalidomide or Pomalyst in the last few years. These drugs are called immunomodulatory agents because they help boost the immune system and take away the part of the immune system that suppresses it from eliminating myeloma. They have a multitude of other ways that they work to knock out myeloma. They reduce blood vessels that feed the myeloma. They can kill myeloma directly as well and they “make the neighborhood in which the myeloma cells grow less hospitable” for the cancer cells to increase.

Although somewhat active as single agents, their effectiveness is greatly boosted when they are combined with steroids. They also are more effective when combined with Velcade and Kyprolis as well as other chemotherapeutic agents. More recently, they have been shown to have enhanced anti-myeloma effects when they are combined with a variety of monoclonal antibody treatments. The other good news is when they are combined, their doses can be reduced; and, as a result, they can have less side effects.

The side effects of thalidomide are peripheral neuropathy which manifests as numbness, tingling, and sometimes burning pain. Unfortunately, in contrast to Velcade-induced peripheral neuropathy, these effects are often irreversible. All of these drugs can also cause constipation but also diarrhea after long term use. The latter adverse event can often be improved with the use of bile acid binding agents such as cholestyramine. The drugs certainly can increase the risk of blood clots especially when combined with steroids and some types of chemotherapy including Doxil or doxorubicin. Also, rashes can occur early in the treatment but often resolve quickly after a short break in their usage.

The drugs are very active and can be given for a long period of time but there seems to be small risk of secondary cancers especially skin cancers and more rarely some types of leukemia. The risk of secondary cancers is more often observed among those who receive these drugs who have also been previously treated with an alkylating agent such as melphalan.

Their ability to lengthen lives in myeloma patients far outstrips their low risk of the patient developing another type of cancer. Side effects of these drugs may also include tiredness as well as inability to think clearly. But lowering the dose certainly helps overcome those effects, and when these drugs are given in the evening that can help as well.

Since the drugs are cleared in the kidney, patients may require a reduction in the dose if they have reduced kidney function. We know that’s true with both Revlimid and Pomalyst. Importantly, the drugs certainly can be given safely and be effective for patients with poor kidney function but should be administered at lower doses for those individuals. The drugs also increase the risk of blood clots especially when combined with steroids. In terms of reducing the risk of blood clots, patients should take a baby aspirin daily in order to help prevent this problem from occurring. Patients with a prior history of blood clots or other risk factors for clots may need to take other stronger medications that reduce clots such as Eliquis, Pradaxa or Xarelto to prevent these types of complications.

Overall, IMiDs are a highly active class of drugs and even more effective when combined with the other classes of drugs used to treat myeloma including chemotherapy, steroids, PIs, and monoclonal antibodies.

Recently, a variety of immune-based therapies have been shown to be highly effective for treating myeloma patients. The types of treatment and their target proteins vary but they all show encouraging effectiveness although their side effects differ.

First, monoclonal antibodies that target surface proteins highly expressed on myeloma cells made their way into the clinic. Specifically, both CD38 and SLAMF7 serve as targets for these antibodies. These proteins are highly expressed on the outside of myeloma cells, but on few other types of cells in the patient. This “targeting” of the treatment with these monoclonal antibodies to the tumor cell without impacting other types of cells makes these drugs ideal. They elicit an immune response that results in the elimination of myeloma cells. The antibodies have also been shown to boost immune responses in quite different ways. Treatments targeting CD38, daratumumab (Darzalex or Faspro) and isatuximab (Sarclisa), rid the bone marrow of cells that turn off the immune response unleashing an enhanced way for the bone marrow to be rid of myeloma cells. The antibody targeting SLAMF7, elotuzumab (Empliciti), turns on a type of white cell called a natural killer cell that can bolster the immune response in its attempt to kill the tumor cells.

Elotuzumab or Empliciti with dexamethasone has been reported to be only active when combined with either the IMiD Revlimid or Pomalyst. However, this drug may also be active in some patients when the two drugs are used without these IMiDs. Without the IMiD, this combination is much better tolerated with few side effects. However, this monoclonal antibody is much more effective when it is used in combination with an IMiD. The drug is administered intravenously. Empliciti has minimal side effects with a small minority of patients experiencing what are termed infusion related reactions consisting of flu-like symptoms during the first infusion which are rarely of any significance.

Both the CD38-targeting monoclonal antibodies daratumumab and isatuximab have shown activity for treating myeloma in many clinical settings. Daratumumab may be administered either intravenously (Darzalex) or subcutaneously (Faspro) whereas isatuximab (Sarclisa) is only given intravenously. Both antibodies are active when combined with oral dexamethasone. Sarclisa improves the effectiveness of other myeloma drugs including Pomalyst and Kyprolis. Daratumumab has shown to increase the effectiveness of many other anti-myeloma drugs, including not only Pomalyst and Kyprolis but also Revlimid and Velcade. Moreover, this latter anti CD38 monoclonal antibody has been shown to improve outcomes for patients in not only the previously treated setting but also for patients who have received no prior treatment when it is combined with dexamethasone and Revlimid, and also when Velcade is added to those two drugs. These antibodies are associated with higher rates of infusion reactions than Empliciti, but these usually only occur during the first infusion and uncommonly prevent ongoing administration of these treatments. When used in combination with PIs or especially IMiDs, the antibodies show increased side effects especially low blood counts that may be associated with high rates of infection from low white blood cell counts and reduced normal protective antibody levels. In some cases, severe bleeding may occur in association with low platelet counts. Thus, patients’ blood counts need to be carefully monitored when receiving these antibodies and patients must be watched carefully for signs and symptoms of infection or bleeding.

Also, all of these drugs can complicate the interpretation of the tests used to monitor myeloma patients since they are monoclonal antibodies and can be seen as small M proteins when protein electrophoresis is performed that are not really coming from the myeloma tumor cells. In addition, blood typing can be more difficult among patients receiving either daratumumab or Sarclisa making transfusion of blood a harder task to accomplish.

More recently, the antibodies have been made in such a way that they not only target the myeloma cells but the immune cells as well which are known as “T-cells.” This so-called bispecific antibody brings the tumor cell next to the killer T-cell making it more convenient and effective as an immune treatment. Teclistamab targets B-cell maturation antigen (BCMA) which is present on only myeloma cells and CD3 which is on the T-cells. This treatment has shown effectiveness in heavily previously treated patients. However, since BCMA is also present on normal plasma cells that produce antibodies that fend off infections, many patients develop severe, life threatening infections. Also, the immune response that occurs during treatment may become uncontrolled and lead to side effects known as cytokine release syndrome (CRS) early in the treatment that can be quite troublesome. These may sometimes be controlled with antibodies that target interleukin 6 such as tocilizumab. Also, significant neurologic side effects may also develop in some patients. As a result, these side effects have led to the requirement for administration of these treatments initially to be done in the hospital.

The use of T-cells that target myeloma have led to the use of these treatments for late-stage myeloma. The treatments are called “CAR T-cells” and also target BCMA and include a construct in the cell that turns on the T-cell so that can elicit a strong immune response to eliminate the myeloma cells. Both Ide-cel and CARVYKTI are now used in the clinic. It takes a number of weeks to manufacture these types of T cells during which the patient’s myeloma must be controlled. These treatments can be quite effective but are also fraught with similar complications (CRS and neurologic) that have been observed with the bispecific antibodies. Thus, the treatments require administration and observation in a hospital setting. The availability of this treatment modality has been limited by manufacturing capabilities but hopefully that will improve soon.

So, what’s happening in myeloma today in terms of new agents? There is an explosion of new drugs that are now used to treat myeloma and ones in development.

Selinexor or Xpovio is one of the new drugs that has become recently available. It is a pill that is taken weekly. The drug is in a new class of drugs that blocks proteins from getting out of the nucleus and into the rest of the cell called the cytoplasm. By keeping these proteins in the nucleus, myeloma cells cannot survive. Selinexor works with steroids, but its effectiveness is much improved when these two drugs are combined with other agents such as the PI Velcade. Promising results with other combinations have also been shown.

Venetoclax or Venclexta is a pill that is taken daily and has been widely used to treat certain types of leukemia and lymphoma. It targets a cancer gene called Bcl-2. It turns out that about 20% of myeloma patients show a genetic abnormality known as an 11;14 translocation in which parts of these two chromosomes combine in an abnormal way. These patients’ myeloma tumor cells are very sensitive to treatment with this drug, and they show high response rates when treated with this drug alone. In the subgroup of patients with this genetic abnormality, venetoclax has also been effectively combined with other active myeloma drugs, including anti CD38 antibodies such as daratumumab and Sarclisa as well as PIs including Velcade and Kyprolis.

There are so many other new agents in development. Antibodies targeting other proteins are being studied. Antibodies that are combined with drugs are also in early development. These new treatments can deliver the drug only to the cancer cell because only the cancer cell expresses the target of the antibody. Thus, the antibody binds the cancer cell with the drug attached. The drug can be released and get right into the cancer cell; and, furthermore, it also helps immune cells in the neighborhood of the tumor to be more effective to eliminate the myeloma cells without causing off target effects on other healthy cells in the body. Thus, we can potentially deliver therapy that is truly tumor-specific and leave the rest of the patient alone. Other targets for use as CAR T-cells are also in development.

We also are finding ways to target other proteins on the surface of myeloma tumor cells and identifying other key pathways within the myeloma cell that may be blocked. These include the PI3 kinase inhibitors as well as the histone deacetylase inhibitors. These latter drugs do not seem particularly active alone, but they may help other drugs to work more effectively such as the PIs and IMiDs. Recently, a class of drugs called JAK inhibitors that are currently used to effectively treat auto immune diseases, skin disorders and certain blood diseases, have recently been shown to be effective for some heavily previously treated myeloma patients and can overcome resistance for patients who have failed IMiDs. All of these new types of drugs are works in progress presently and we hope over the next few years we learn how to use these agents so we can attack the myeloma cell and leave the rest of the body alone. We also hope to determine how to use these drugs with other drugs that have already been effective to improve outcomes for myeloma patients.

So how do we know if the treatment is working or not working? Well, we cannot directly measure the amount of the tumor cells themselves because they are spread throughout the bone marrow, so we are unable to accurately measure their amount there. So, instead we measure the product of the tumor cells which is the monoclonal antibody marker. Most patients have it in their blood but some patients (around 15%) have the protein as only part of the antibody known as the light chain (see below) which may be in the blood and urine.

Thus, the doctors will monitor your disease using several tests to measure the levels of these proteins to determine whether the treatment is working or not. They will watch for changes in the monoclonal protein levels in the blood and urine using a technique called protein electrophoresis which separates proteins in the blood and urine based on their size and charge. Another way to measure those same protein levels is by determining the amount of the type of antibody in the blood that makes up the monoclonal antibody – e.g., IgG levels if the patient has IgG myeloma, IgA levels if the patient has IgA myeloma, etc. A newer test to evaluate the monoclonal antibody measures only part of it called the light chains. Antibodies are made of two pairs of light and heavy chains. Light chains are often made in excess in the myeloma cells; and, thus, cannot pair with heavy chains. Sometimes, all of the patient’s myeloma tumor cells make only light chains. In either case, these so called “free” light chains can be measured in the blood. Changes in these levels correlate with changes in the amount of myeloma in the patient. Light chains can be kappa or lambda so that for each patient’s myeloma tumor cell, only one type of this chain is produced. Thus, one can track the myeloma through changes in these levels as well as determining the differences between the involved type and the other type of light chain - e.g., the difference between the lambda level for a lambda-producing myeloma and the levels of kappa. Also, sometimes the ratio between these two types of light chains is used to assess the patient’s disease.

So, when we measure the reduction in monoclonal protein levels, we can designate different degrees of a response. For example, if it’s 25% - 49% below where it was when you started a new treatment, it’s called a minimal response. Fifty to 89% is a partial response and greater than or equal to 90% but not all gone is considered a very good partial response. If the protein markers completely disappear, that is considered a complete response, but this must be confirmed with examination of the bone marrow (see below). The urine tests used to determine responses are used a little differently to designate different types of response. A 24-hour urine collection is required. At least a 50% but less than 90% reduction in the monoclonal protein level is considered a minimal response, and more than 90% but some protein remains is a partial response. Most patients respond to their first treatment, and many achieve a complete response so that the monoclonal protein cannot be identified. However, the achievement of a complete response does not mean the patient is cured. It certainly can come back over time.

A new blood marker is also gaining interest called serum B-cell maturation antigen (sBCMA). This protein is found at high levels on the surface of myeloma tumor cells. It is shed into the blood and can be used to predict outcomes for myeloma patients and monitor their course of disease. sBCMA can also be used to predict the risk of MGUS or smoldering multiple myeloma to develop active myeloma requiring treatment. Since it is a different protein than the monoclonal antibody, this biomarker can also be used to track the disease course of those patients with nonsecretory myeloma who do not produce a conventional monoclonal antibody marker. It also appears that sBCMA can more quickly determine when a patient’s disease is worsening than conventional markers which will allow patients who are failing their current treatment to change to another therapy more quickly. This blood test is still considered a research tool.

Bone marrow examination can be used to assess the status of the myeloma. Because of the differences in the amount of marrow involvement, i.e., percentage of myeloma tumor cells, throughout the bone marrow, it is not often used to follow patients for routine monitoring. Its use is usually limited to patients showing low blood counts in which this evaluation may help differentiate whether this is from myeloma involvement or overtreatment with drugs. It is also used to confirm the absence of myeloma cells for patients whose monoclonal protein becomes undetectable and free light chain levels become normal. However, the differences throughout the bone marrow in myeloma cell involvement that occurs in most patients as mentioned above, limits its ability to truly define absence of myeloma cells in a patient.

Recently, development of more sensitive assays to determine whether minimal residual disease is present in the bone marrow have gained interest. These assays are much more sensitive to detect small amounts of myeloma in the bone marrow. They may rely on genetic- or flow-based assays of whole cells derived from bone marrow samples. The usefulness of these tests are limited by the marked differences in marrow involvement with myeloma in different parts of the marrow compartment and the specificity of these tests in identifying true myeloma tumor cells. Overall, these tests show that patients with so-called minimal residual disease negativity have improved outcomes.

Other ways to determine the status of the myeloma are to track changes in the kidney function although this may be problematic because there may be other causes for impaired function of the kidney that are unrelated to myeloma. Blood counts can be monitored and worsening of these may also often be from other causes. For example, treatments can lower the blood counts. Anemia may also be caused by low iron or B12 levels that have nothing to do with myeloma.

Certainly, radiologic imaging can be useful to find changes in the patient’s clinical status. However, routine use of these procedures including bone surveys, PET CT scans and MRIs are not recommended. Importantly, these tests may be necessary for cases where new symptoms related to bone disease develop.

The good news is today there are so many options so when it comes back when we say, “Okay, it’s progressing?” If the monoclonal protein marker goes up by 25% or more, we consider that the patient’s disease to be worsening or what we call progressing. In many cases, it is obvious that the treatment is not working even if the marker does not increase by 25%.

It is also important to not only consider whether the treatment is working but whether you are tolerating the treatment. In many cases, reduction in doses or schedule of the drugs can help the patient stay on a treatment that is effective.

“So, if I’m being treated, how long do I have to stay on the treatment?” The data is emerging that maintaining the remission with 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 lenalidomide (Revlimid) have shown an improvement in myeloma patient’s survival with their long term use. We also use other IMiDs long term such as Pomalyst and PIs including Velcade, Kyprolis and Ninlaro. The long-term use of these drugs is relatively safe although their effectiveness as maintenance treatments has not been completely established. The monoclonal antibodies are also gaining use as long-term treatments to control myeloma without signs of showing significant side effects.

When these drugs are used in the maintenance phase of treatment, lower doses are administered using longer dosing intervals. This adds to the convenience for drugs that must be administered in the clinic. However, that does not have to be the case with oral agents such as Revlimid and/or steroids. Maintaining the remission is a key part of the treatment plan through maintenance therapy. During maintenance therapy, patients’ myeloma labs are generally monitored on a monthly basis to assure that they are continuing to respond without signs of their disease worsening or other side effects developing from the treatment.

If the patients have been on chemotherapy agents, such as anthracyclines, including doxorubicin and Doxil or alkylating agents such as melphalan, cyclophosphamide and bendamustine, these are discontinued when maintenance therapy begins. This avoids the known long-term negative effects of these drugs that may include permanent damage on bone marrow and heart problems for those receiving Doxil or doxorubicin.

You may be asked to participate in a clinical trial; and, thus, want to learn what clinical research is before you even decide that you want to participate. In general, this involves the testing of drugs that we hope will help many patients, like you, with myeloma. So, we conduct 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 phases ranging from phases 1 to 4. In phase 1, 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 regarding whether the drug has clinical benefit for patients. In phase 2 trials, now that we know the proper dose that is safe and well tolerated, we evaluate them on more patients to establish more precisely their effectiveness. Next, we conduct a phase 3 trial in which we randomize patients to receive either the tried and-true gold standard treatment compared to the new treatment. Finally, in phase 4 trials, now that we know that the new treatment is better than the gold standard, other studies are conducted to adjust doses and schedule of the drug(s) and evaluate the treatment for specific types of patients. This helps better define the most effective ways to use the drug(s).

There also may be trials that are called “PK” or “PD trials.” So, what are these types of clinical studies? These are pharmacokinetic (PK) or pharmacodynamic (PD) trials which test not necessarily whether the drugs work but correlate the drug levels with their effectiveness. They also evaluate other measures of outcome that may help better define how they work besides just measuring the conventional ways to assess the status of the patient’s myeloma. All these types of trials help teach us in a way that will ultimately help many patients like yourself.

So, for you to decide about whether you want to participate in trials, you have to consider if you want to be part of the extra effort require in which you may be asked to have additional blood draws, come to clinic more often for those blood draws, and participate in other extra tests that are part of the trial. You must weigh that against the possible benefit for you and help you are providing to many other patients like yourself over the long run. Overall, clinical trials are a great thing to participate in for most patients. After all, treatments used today resulted from participation of many patients in clinical trials in the past. This has led to not only marked improvement in the length of lives for those with myeloma but just as important their quality of life as well.

Now that we’ve learned about what myeloma generally is and how to treat it, let’s discuss the specific clinical manifestations of the disease.

Bone Disease:

The most important and frequent clinical problems are related to bone disease. Patients with myeloma lose increased amounts of bone. That is because the “Pac man” cell in the bone called the “osteoclast” is stimulated by the myeloma tumor cells to actually get rid of bone. Our job is to stop the bone “gobbling up” 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 shown to dramatically reduce the risk of fractures and spinal cord compression as well as these patients’ requirements for radiation or surgery to bone.

Thus, the use of both radiation and surgery for bone problems related to myeloma has been greatly reduced today because of the effective use of these drugs. These drugs are very potent; they can have a negative impact on the kidney so it’s important that patients have monthly monitoring of the kidney function.

Today, we have another effective option for patients who have kidney problems or develop them from bisphosphonates or other drugs. Denosumab or Xgeva is administered on a monthly basis by subcutaneous injection and has similar benefits in reducing bone-related complications to the bisphosphonates.

Infrequently, patients may have jaw problems from all of these agents resulting often from surgical procedures especially the extraction of teeth or dental implantation procedures. These types of procedures should be avoided among patients receiving these drugs. Thus, maintaining excellent dental health is a key to making sure these drugs not only are effective but in order to reduce the risk of jaw problems that can occur with the use of these drugs.

Not only can we show effectiveness with drugs such as bisphosphonates for treating myeloma bone disease, 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 since many of them are vitamin D deficient. So simply the usual amounts like 800 international units per day may not be sufficient for a myeloma patient who is vitamin D deficient. Frequently, myeloma patients may require increased amounts of vitamin D to achieve levels that are in the normal range.

In addition to medical management using treatments with drugs, vitamins, and calcium, we also may have you seen by an orthopedic or back surgeon. They can help assess your bone disease - do you need surgical intervention, or help from a physical therapist or rehabilitation physician? Remember the oncologists and hematologists are trained in diseases of the bone marrow and not the bone which requires the expert input of an orthopedic or back surgeon.

Staying active is very important, especially weight-bearing exercise which keeps your bones healthy and strong. Without use, more bone loss will occur putting you at higher risk of developing fractures. Overall, keeping your bones healthy and happy over the long run requires an integrative approach not only involving regular exercise and treatment with drugs like bisphosphonates or denosumab or vitamins like vitamin D or minerals like calcium but also often the involvement of an orthopedic or back surgeon, physical therapist, and rehabilitation medicine physician as well. Occasionally, patients may require radiation therapy to relieve bone pain or treat fractures, but this form of treatment is being used less these days with the effective use of bisphosphonates and denosumab and the surgical interventions that are now available through our orthopedic surgical colleagues.

Anemia:

It’s likely that sometime during the course of your myeloma that you will become anemic. So, what is anemia? It means your red blood cell count is low. What does that do to you if your red blood cell count is low? Red blood cells carry oxygen, so if you don’t have enough oxygen, you will feel weak and tired and may become short of breath. We will do everything we can to prevent this from happening. It turns out there may be a lot of reasons why anemia may develop in a myeloma patient. It may be the myeloma itself is causing it, so you are unable to make red blood cells in your bone marrow and they are no longer available to go out into the blood. After all, the red blood cells are made there, and the myeloma tumor cells are lurking there. They may shut off your ability to make red blood cells by producing substances that stop their production. Anemia could also be due to the treatments such as chemotherapy, other myeloma drugs or radiation therapy. It also may be that your kidneys are not working well from myeloma or other causes. Because of this, you are not making the red blood cell growth protein called erythropoietin or EPO which is produced in the kidney. Without EPO, you’re going to become anemic.

How do we monitor for anemia? We simply measure the number of red blood cells in your blood. We measure it using three assessments - amounts of blood levels of hemoglobin, hematocrit, and number of red blood cells. If the count is very low, we’re going to want to either transfuse you or give you some supplements to help improve your red blood cell count. The most effective growth factor we have right now is called EPO itself. This is commonly administered in several forms today, Aranesp, Retacrit or Procrit. All of these can boost the level of red blood cells in the blood. But we have also learned over the last several years many patients with myeloma are iron deficient from causes that have nothing to do with myeloma. In fact, simply giving EPO isn’t enough to improve red blood cell counts in that case. They need iron as well, especially intravenously administered iron. Often, these patients are found to have a source of bleeding, especially in the gastrointestinal tract. Other patients may be vitamin B12 deficient and taking this vitamin may reverse anemia in those cases. Sometimes, patients may have a destructive process causing their anemia called hemolysis. Steroids and antibody treatments can help reverse this process.

If patients have received many transfusions of red blood cells, they may become iron overloaded. This can cause serious problems in the heart, liver, and other major organs. We have drugs to help with that problem including Exjade.

Proper monitoring of your red blood cell counts is key to the long-term success of your myeloma treatment. Recently, there’s concern that the use of EPO for patients with myeloma and other types of cancer is actually speeding up the cancers’ growth and shortening the survival of these patients. There are ongoing studies currently evaluating this. Some have shown that this is the case, and some have not. For that reason, you don’t want to go overboard with the use of EPO drugs like Procrit, Retacrit or Aranesp. Your doctor will work with you to make sure you’re only receiving it when you absolutely need to. We want to make sure that you have proper levels of circulating red blood cells, so that you have good energy levels. We don’t want to overdo it, however. So, make sure your doctors are measuring your hemoglobin level on a regular basis and treating you with either drugs like Procrit or Aranesp or, if necessary, transfusions so you have good energy.

Infections:

Myeloma patients are at higher risk of developing infections because of their impaired immune system. The reasons for this are multiple. Patients with myeloma show reduced levels of antibodies that protect them from infections. This results from the disease itself as well as treatments especially the monoclonal antibodies that target both the plasma cell that is cancerous but also the noncancerous plasma cells; the latter normally produce the protective antibodies that prevent and fight off infections. In addition, functions of other immune cells such as T-cells and natural killer cells are impaired putting patients at higher risk of developing many types of infections. Sometimes, the bone marrow is filled with myeloma tumor cells that reduce the production of a protective type of white blood cell called a neutrophil. Many treatments can also frequently result in a reduction in the amounts of these cell types. When the levels of these types of cells are low, patients are at high risk of developing many types of serious infections. Use of growth factors such as G-CSF can help increase levels of these cells in the blood and prevent these infections from occurring. Use of intravenous immunoglobulin for patients with low normal antibody levels may be helpful for some patients who have frequent infections. Also, some groups use antibiotics to prevent these infections but studies to show their effectiveness for reducing the occurrence in this clinical setting are lacking. The viral infection shingles from reactivation of the herpes zoster virus that causes chicken pox occurs more frequently among myeloma patients who receive treatment with many of the different myeloma drugs, including PIs and monoclonal antibodies. As a result, patients taking these drugs are often given low doses of antiviral medications including acyclovir, Valtrex or Famvir while receiving these drugs which markedly reduce the occurrence of this type of viral infection. Patients with myeloma are at higher risk to develop serious complications and death from infection with COVID 19. They show impaired immune responses to vaccination as well. Use of antiviral drugs such as Paxlovid has shown effectiveness for treating patients infected with COVID-19.

Overall, careful monitoring of blood counts is important for myeloma patients and attention to symptoms related to infection should be part of the routine care of myeloma patients.

Kidney Disease:

Another frequent problem with your myeloma involves its effects on the kidney. Your kidneys may be negatively impacted directly by the myeloma cells, the myeloma’s monoclonal antibody or its light chains that are produced by the tumor cells or its breakdown products called amyloid. Also, sometimes patients may develop dangerously high calcium levels from the release of calcium from their bones which can damage the kidney. There may be drugs you are receiving for the myeloma that impair the function of your kidneys. Drugs like the bisphosphonates, antibiotics, or other treatments for the myeloma may have negative effects on kidney function. Frequently, myeloma patients may also have other diseases that cause kidney problems such as diabetes mellitus or hypertension. It is important to make sure those diseases are under optimal control, so you are not negatively impacting your kidney function further from these other diseases’ impact on your kidneys.

To reduce the impact of kidney disease most effectively, it is important that you see a kidney specialist if you have significantly reduced function of this organ. They help a lot with management of your fluids and acid, potassium, and phosphate levels as well as other minerals that may be impacted by impaired kidney function. We want to prevent irreversible kidney function that results in chronic dialysis for the patient. Keeping yourself well hydrated is always important.

So, kidney disease commonly occurs in myeloma patients and reducing its negative impact on the patient first and foremost involves rapid and effective treatment of the myeloma. In some cases, plasmapheresis has been used to reduce the levels of the kidney toxic antibodies in the blood. However, its ability to improve outcomes for myeloma patients with severe kidney problems has not been clearly shown. You also will need to take proper doses of drugs adjusted for your kidney function when it is not normal. This may require reduction of not only drugs to treat your myeloma but some of your other medications as well. It also may require avoidance of drugs that may be associated with kidney problems such as bisphosphonates or NSAIDs like ibuprofen or Naprosyn.

Nerve Problems:

Nervous system problems commonly occur among myeloma patients. They may involve the central nervous system, in other words your brain, from drugs we use to treat the myeloma. For example, IMiDs such as thalidomide may make you sleepy and tired. More frequently, these types of nerve problems involve your peripheral nervous system which include the nerves in your hands, feet, arms, and legs. Patients often develop peripheral neuropathies which are manifest as numbness, tingling, and less often pain in their hands and feet. Sometimes, patients may develop muscle weakness. This complication may be from the antibodies themselves that can coat the nerves and cause them not to function properly. Sometimes, removal of the antibody is attempted using plasmapheresis in which the antibody that is causing the problem is removed from the blood.

Today, peripheral neuropathy is most frequent from the medications we use to treat myeloma. Velcade and thalidomide often cause nerve damage resulting in peripheral neuropathy. Velcade-induced peripheral neuropathy is more often reversible whereas IMiD-induced problems are generally irreversible even following discontinuation of the drug.

Treatment of this problem may include drugs such as Neurontin or Lyrica. Other drugs used involve Cymbalta and doxepin. In addition, over-the-counter medications may help. For patients who receive IMiDs or the PI Velcade, alpha lipoic acid is continued during treatment with these agents to reduce the risk of neuropathy developing and its severity.

In addition to drug-induced neuropathies, infections can cause nerve problems. Specifically, shingles or herpes zoster is the most often cause of viral-induced nerve problems in myeloma patients. This develops because of reactivation of the chicken pox virus. Prevention of this infection can be accomplished with use of low doses of antiviral drugs such as acyclovir, Valtrex and Famvir.

It is very important to let your doctor know if you are experiencing any problems with your nerves especially if you are on drugs that may be causing this complication. Lower doses and less frequent dosing may improve these symptoms. Sometimes discontinuation of the offending drug will be required and substitution of another agent without these side effects can be used. For example, those with severe symptoms from Velcade peripheral neuropathy may be treated effectively with another PI such as Kyprolis without experiencing this complication. So, communication with your healthcare professional is the key which will lead to optimal long-term benefits from the drugs you’re receiving for myeloma while at the same time minimizing their side effects.