Myeloma Treatment and Side Effects Management Update

Transcription

1 1 Slide 1: Myeloma Treatment and Side Effects Management OPERATOR: Hello, everyone, and welcome to Myeloma Treatment and Side Effects Management Update, a free telephone/web education program. It is my pleasure to introduce your moderator Mabel Maia of The Leukemia & Lymphoma Society. Slide 2: Welcome and Introduction Hello, everyone. On behalf of The Leukemia & Lymphoma Society, a warm welcome to all of you and a special thank you to Dr. Melissa Alsina and Ms. Kathy Daily for sharing their time and expertise with us today. We have over 1,800 individuals participating from across the United States and many international participants from Argentina, Canada, Croatia, Guatemala, India, Ireland, Jamaica, Kenya and United Kingdom. We would like to acknowledge and thank Celgene Corporation, Millennium: The Takeda Oncology Company, and Onyx Pharmaceuticals for their grants to support today s program. I am now pleased to introduce Dr. Melissa Alsina and Ms. Kathy Daily. Dr. Alsina is Head of the Multiple Myeloma Program. She is Associate Member in the Department of Blood and Marrow Transplantation. Ms. Daily is Multiple Myeloma Bone Marrow Transplant Coordinator and Primary Nurse. They re both from H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida. Dr. Alsina and Ms. Daily, we are so privileged to have you with us today and I now turn the program over to Dr. Alsina. Slide 3: New Advances in the Treatment of MM Thank you so much for that introduction. I want to thank The Leukemia & Lymphoma Society for organizing this program and all of you for joining us. So what I will do is I will talk to you today a little bit about myeloma and then go into some of the novel therapies that we have available nowadays. Slide 4: What is Myeloma? So what is myeloma? Just a brief introduction. Myeloma is a cancer of the plasma cells. The plasma cells are cells that we all have. They re part of our immune system and their normal function is to produce antibodies or proteins to help us deal with infections. So these cells can grow, in the majority of the cases we don t know what the cause is, and they grow and then they usually grow inside of the bone marrow and they keep producing abnormal proteins in very high amounts. These proteins can actually damage the kidneys. Some patients with myeloma can present with kidney failure. The myeloma cells grow in the bone and they can cause bone destruction, so patients with myeloma frequently can present with what we call bone lesions and bone pain. They don t let the bone marrow function normally, so patients with myeloma can also present with anemia or low red cell counts. And they can also have a high calcium in the blood because of the bone destruction.

2 Slide 5: Epidemiology It is a relatively rare disease. There were in 2010, there were about 20,000 new cases of myeloma diagnosed in the United States. And it s about 15 percent of the cancers of the blood. It s a disease that usually affects older people, so the median age of diagnosis is about 70. And 99 percent of the patients are going to be over 40. Being a myeloma doctor, I see many myeloma patients. My youngest patient actually is 25. There s an increased incidence in African-Americans. It s twice as common compared to Caucasians. And we don t know really the reason for that. And in general it s not a disease that is hereditary or can be passed in families, even though we have seen some clusters in families. Environmental risks that have been described are pesticides, very significant exposure to pesticides, radiation exposure, Agent Orange, but in general in the majority of the patients we really cannot identify what causes the disease. Slide 6: Age-Specific Incidence Rates In the next slide, for those of you that have the slides, is just a graph showing the incidence per age. And as you can see the majority of the patients are going to be older than 70, as I already mentioned. Slide 7: Diagnosis Patients with myeloma, in their presentation, usually they will present with anemia or low red cell counts and when a patient has anemia the patient will usually be very tired and have fatigue. Bone pain we see probably in about 80 percent of the patients at diagnosis. Sometimes it s associated with fractures that happen, spontaneously without significant trauma to the bone. Twenty-five percent of the patients will have renal failure. That means kidney disease. And about the same amount will have a high calcium. And because the cells that cause myeloma are part of your immune system, when they re not working normally, then your immune system becomes weak and patients with myeloma frequently present with multiple infections or frequent infections. Slide 8: Diagnosis To make a diagnosis of myeloma, the most important test is the bone marrow aspiration and biopsy because we have to show that these cancer cells are growing in the bone marrow. But besides that, it s very important to look at the blood count, look at the blood to check the calcium, the kidney function. And we also do some very special protein studies to look at the levels of these proteins. And this is very important because measuring these proteins in the blood and in the urine give us the best way of measuring the disease activity. So we would know a level of the protein at diagnosis and the way we would know if a patient is responding to treatment is to measure that protein after treatment and seeing that the protein is going down. We also do some special tests from the bone marrow to look at the genetic abnormalities in the myeloma cells and that is very important in terms of prognosis. 2

3 Slide 9: Skeletal Survey Typically we do X-rays of the bone to look at all the bones. We call that a skeletal bone survey. And frequently we can identify in the bone survey what we call lytic lesions that are like black holes in the bone, indicating areas that are involved by the myeloma. Slide 10: Diagnosis Sometimes we have to be a little bit more thorough with that, if we don t see any changes in the X-rays, we have to do more special tests like an MRI or a CT scan or a PET scan, to take a better look at the bones. Slide 11: Myeloma Continuum So myeloma, once you make the diagnosis of myeloma, which would be made if there is increased plasma cells, these cells in the bone marrow, to more than 10 percent, then we have to decide if the disease is active or the disease is what we call smoldering or indolent myeloma. Patients with smoldering myeloma are patients that have myeloma because they have more than 10 percent plasma cells in the bone marrow. They have increased levels of the protein in the blood. However, they are not having any symptoms related to the disease. So they do not have hypercalcemia, anemia, kidney problems or bone disease. These patients usually are diagnosed incidentally actually because someone found that maybe they have mild anemia or maybe they have an elevated protein in the blood. And from the information that we have right now, patients with smoldering myeloma should be observed, even though at this point there are some studies ongoing, looking particularly at patients that have smoldering myeloma that we think are at a high risk of progressing quickly. And there s a question whether those patients need to be treated or not. But in general smoldering myeloma should be observed very closely. In contrast to active myeloma, where patients have symptoms or organ damaged associated with the disease and those patients should start therapy as soon as possible. Slide 12: Staging and Risk Stratification Once we make a diagnosis we do what we call staging, which is to determine what I was just talking about, a little bit about the prognosis of the disease and whether a patient is symptomatic or not and needs therapy. And we also do some special tests to stratify the patients according to the risk. Slide 13: Staging For staging we have two staging systems, the International Staging System that looks at a protein in the blood that is called beta-2 microglobulin and also the normal protein, which is called albumin, is stage I, II and III. And we do these tests to actually get prognostic information about the disease. 3

4 Slide 14: Staging The Durie-Salmon Staging System is also stage I, II and III and actually gives us information as to whether the patient has very active myeloma in terms of symptoms, looking at the hemoglobin, at the bones, at the protein level. A patient that has Durie-Salmon stage I usually does not have any symptoms, has smoldering myeloma, should not be treated. Patients with Durie-Salmon stage II and III should start therapy. Slide 15: Prognosis In terms of the prognosis, the most important prognostic indicator right now is some special test that we call cytogenetics and FISH, that we do in the bone marrow and we do the bone marrow and that classifies a patient as having high risk myeloma and standard risk myeloma. Patients with high risk myeloma frequently respond to therapy, but the response is shorter than patients with standard risk. And we still are doing research trying to find out better ways of treating this group of patients. Slide 16: Prognosis And there s a special test that you might have heard about where we do like gene expression profile in the cancer cells. This is a test that came out recently and we ve been doing it for prognostic information, but we still don t know very well how to use this to decide therapy. So it s a test that we can do for information, but it s really not going to dictate which therapy a patient should get, at least for now. We hope that in the future this test, looking at gene expression profile, will be able to dictate how we treat the individual patient. Slide 17: Response Criteria In myeloma we talk about response, how a patient responds. As I mentioned before, the best way to look at this is to look at the protein level. And we have categories of response. So you might have heard things like CR, meaning complete response, or VGPR, which means very good partial response, or PR, which means partial response. And these are all categories that have been developed based on the protein levels. So for example, a partial response would be that there s more than 50 percent reduction in the protein level. A very good partial response would mean that there s over 90 percent reduction in the protein level. And a complete response means that the abnormal protein is completely gone. So there s no abnormal protein in the blood or in the urine. Nowadays with the new therapies that we have, we re actually happy to say that we can get about 70 percent of the patients to be either in a very good partial response or complete remission. And the goal of therapy should be to get patients in complete remission because we know that patients that can achieve a complete remission or a complete response can live longer and stay longer with the disease under control. And this is especially important in patients that have high risk myeloma. The good news is that we are able to achieve this in a very high number of patients nowadays. Before we had the new agents, we were only able to achieve complete remission in about 3 percent of the patients and after autologous transplantation, in about 30 percent of the patients. And now we re talking with the new drugs, we re able to achieve complete remission without transplant in about 25 to 30 percent of the patients, and that is upgraded to about 60 percent of the patients after transplant. So the new therapies have helped definitely in the survival and treatment of myeloma. 4

5 5 Slide 18: Our Growing Agents in MM So the one slide that I m showing now has a list of drugs and this is just to give you a general idea of what are the different classes of drugs that we are now using in myeloma. And we have a number of new drugs that are proteasome inhibitors like bortezomib or Velcade. We have drugs that are immunomodulatory drugs like thalidomide and lenalidomide. We have other new drugs and then we still have the traditional agents, the old chemotherapy, which actually works very well in myeloma and we still use it, more commonly in combination with a new drug. Slide 19: Clinical Trials The reason why we have all these new drugs in myeloma is because there are clinical trials. So a clinical trial is a research study that involves people. It is a final step in a long process that begins with preliminary laboratory research and animal testing. So when a drug in the lab or in animal testing is considered to be active in myeloma, then we take that drug to the clinic. But we have to first make sure, number one, that the drug is safe to give, and then we need to test the efficacy of the drug. And the only way we can get a drug approved for clinical use is if the drug has been shown to be safe and effective through a clinical trial. So the reason we have bortezomib or Velcade or Revlimid available nowadays for myeloma patients is because hundreds of patients participated in clinical trials and allowed this to happen. So clinical trials obviously are super important or actually I should say essential in getting any drug approved. But also it allows the patients to have an opportunity to receive a novel therapy. In a clinical trial usually we can do it in combination with a drug that is already standard to try to improve on the efficacy of that drug, or we can do it to test a new drug. I think the more people who participate in clinical trials the faster these research questions can be answered and the faster the drugs will go from the laboratory to the clinic. So again, very important to participate in a clinical trial. And in myeloma in particular, which is a field that is changing very quickly and we have learned a lot, but there s a lot more to learn, it s actually an essential component. Slide 20: Treatment Overview So in general the treatment of myeloma, we can divide the treatment of myeloma in three phases. The first phase is when a patient is initially diagnosed with active myeloma and needs therapy. We call that treatment induction therapy. And usually in general nowadays what we do is we do a combination of drugs, which could be two drugs or three drugs. Usually that regimen contains a steroid and then one of the new drugs and a chemotherapy agent or actually a combination of two new drugs. Probably nowadays the most commonly used induction regimen is called VRD, which includes Velcade, Revlimid and dexamethasone. And the reported response rates with this regimen are close to 100 percent. After that and after we get control of the disease, then we would consider what we call consolidation. And usually consolidation would be doing an autologous transplant, which means we give high dose chemotherapy and after collecting stem cells from the patient and then we rescue the bone marrow from the effects of the chemotherapy by giving the patient back the patient s own cells. And that is an autologous stem cell transplant. And generally in myeloma we use a drug that is called melphalan, which is very active in myeloma, and we give it in high doses.

6 And then usually after transplant, then we consider giving the patient maintenance, which is lower doses of therapy, to try to keep the disease from getting more active. Slide 21: Primary Treatment Algorithm So in terms of the primary treatment, when we see initially a patient, still the main question we need to ask is, is that patient a potential transplant candidate. If a patient is clearly not a transplant candidate and we base this decision on comorbidities, for example, there could be a patient that has very significant heart disease or lung disease and we know will not be able to tolerate the high dose chemotherapy, and then that patient is clearly not a transplant candidate. And we would do a combination of therapy like Velcade-Revlimid-dexamethasone or Velcade-melphalan and prednisone or Cytoxan -bortezomib-dexamethasone. Or we would do a two-drug combination. And you have to discuss that with your doctor and decide what will be the best therapy for you. If a patient is a transplant candidate, then we would give the patient combination therapy as well and we would just try to avoid any treatment that would affect the stem cells. There is a drug that is called melphalan, which is the same one that we use in transplant, but when given in low doses can damage the stem cells, so we don t want to use that if we will consider the patient for transplant. Usually we would give the patient, a potential transplant patient, four to six cycles of the induction, the initial therapy. And after we achieve the best response, then we go collect the stem cells and do the transplant. Nowadays because, as I mentioned before, we can achieve a complete remission in a number of patients with just induction therapy, transplant is being challenged. Some people would ask well, if I am already in complete remission, why do I have to go to a transplant. And we don t know the precise answer to that, but what I can tell you, if a patient has achieved a complete remission, I always give my patients the option of collecting stem cells, storing them and then staying on maintenance, and then considering the transplant later on at time of first relapse. However, if a patient is not in remission or has not had a complete response after induction, then I normally would advise my patient to proceed with transplant, to try to get them in complete remission. As we know, patients that achieve a complete remission can live longer and can stay longer with their disease under control. Slide 22: New Agents & Primary Therapies What about new agents for induction therapy? So as I mentioned before, nowadays the most common regimen that we use is Revlimid, Velcade and dexamethasone. However, some of the new drugs are being tested in combination and show very promising results. Slide 23: CRd: Carfilzomib/Revlimid/Dex One drug that you might have heard of that is called carfilzomib, this drug has the same mechanism of action as Velcade or bortezomib. This drug is not yet approved, but actually will be approved for relapsed myeloma probably at the end of July. And this drug has been tested in combination with Revlimid and dexamethasone in newly diagnosed myeloma patients. 6

7 7 Fifty-three newly diagnosed myeloma patients were treated in this study and if you have the slides you can see that PR, so partial response, was obtained in 100 percent of the patients. So it s a very effective regimen. And even though this is not yet available, this will be the future in getting more patients to achieve a very good partial response and complete remission up front, which is what will actually make us get closer to the cure in myeloma. Slide 24: MRd: MLN9708 Oral Proteasome Inhibitor Another regimen that has been tested is this new drug that is called MLN9708. This is a drug that is like Velcade, but instead of being as an injection, it comes as a pill. It s a drug that is not approved yet, but a study was done combining this drug with Revlimid and dexamethasone and again the response, overall response rate was 100 percent. So again very active regimen that is now in research. Slide 25: Treatment Overview We ll talk now a little bit about maintenance after transplant. Slide 26: What About Maintenance Therapy? So I would say that there s no standard maintenance strategy recommended and this has to be individualized. Slide 27: Lenalidomide Maintenance Recently there were two studies that were done, looking at lenalidomide or Revlimid post-transplant, starting three months after transplant, and those studies were randomized. So in other words, three months after transplant, patients were randomized to receive either no therapy or receive lenalidomide or Revlimid at low doses on a daily basis. One study, which is the one that I m showing in the slide, was done here in the United States and the other study was done in France. And actually both studies show the same results. Slide 28: Lenalidomide Maintenance In the next slide I show time-to-progression, from when the patients were started on therapy. And the patients that did not get the drug, the median time-to-progression after transplant was about two years. Whereas the median time-to-progression in the patients that got lenalidomide had not been reached. So there was a definitive benefit and the patients that were not getting the drug were cross-over to actually get the drug. There was no survival advantage, definitive survival advantage, at least in the French study. In the American study there was a suggestion that there might be some survival advantage. Slide 29: Lenalidomide Maintenance However, there is a concern because in the group of patients that received lenalidomide, there was an increased risk for developing secondary malignancy, secondary cancers. Most commonly cancers were like leukemia, myelodysplastic syndrome. And as you can see in this slide, there were 25 new cancers among 231 patients treated with Revlimid and there were six among 229 patients not treated with the drug. And the median time that patients developed this was about two years. So it was a little bit early to what we would

8 see just with the melphalan from the transplant. And this was actually confirmed in the French study as well. So definitely a concern and we re trying to study this a little bit more carefully and get more information. What I would say for now, if there s a patient that has high risk myeloma, you know, they have the bad abnormal cytogenetic abnormalities in the myeloma cells, or if the patient is not in complete remission, I would advise my patients to go on Revlimid after transplant because I think in those cases the benefits outweigh the risks. However, if there is a patient that is a patient with standard risk myeloma in complete remission, I would not put the patient on maintenance. But again, this is being studied a little bit more carefully and I m sure we ll get more information. But it s something you should discuss with your doctor if you re going to get lenalidomide post-transplant as maintenance. Slide 30: Relapsed/Refractory MM Moving to the relapse-refractory setting, that would mean that a relapsed patient is a patient that received induction therapy, initial therapy, had a response, maybe had a response that was sustained for three years and then the disease gets active again. And how do we treat those patients? Well, we have to look at some characteristics at that point. Sometimes this relapse, that we call, is just maybe a slight increase in the protein and the patients have no symptoms. So we have to consider if the relapse is aggressive or not. We have to consider what treatments the patients have had in the past and what toxicities the patient had, before we decide on the therapy. And also patient preference. I think in the relapsed setting, in contrast to when you re treating a newly diagnosed patient, in a newly diagnosed patient, the goal of therapy is to try to get the patient the best response possible, which would be a complete response or a complete remission. However, in the relapsed setting, the goal of therapy is to try to preserve quality of life. So we want to treat a patient with a regimen that the patient can tolerate well and does not affect the quality of life. Slide 31: New Agents and Therapies So I m going to talk about the new drugs that we have for the relapsed setting. We obviously can use bortezomib and lenalidomide or Velcade and Revlimid for relapse, but I ll just mention some of the new drugs. Slide 32: Pomalidomide Pomalidomide is a drug that is a derivative of Revlimid or lenalidomide, it s a very active drug in myeloma, and there have been several studies done and overall response rates range from about 25 to 40 percent, as a single agent or used in combination with dexamethasone. This drug was just submitted to the FDA for approval, so we expect to have this drug available for patients in the next year or so. Slide 33: Pomalidomide Pomalidomide has also been tested in combination with other agents and if you combine these drugs, you get actually better response rates. So a response rate of 30 percent when you use the drug by itself, or with dexamethasone, when you add another agent like Cytoxan, you can get response rates about 60 percent. 8

9 And the good news is that even though this drug is a derivative of Revlimid, it s effective even in patients that are refractory to Revlimid. So a patient that is no longer responding to Revlimid can still respond to this drug. So that is very good news because it will be a drug that will be available in the future. We are currently at Moffitt conducting a study, looking at the combination of pomalidomide, Cytoxan, and dexamethasone. Slide 34: Carfilzomib I ll just talk a little bit about carfilzomib, which is the new drug that will be probably approved by the FDA at the end of July. And this slide shows the two biggest studies that have been done in myeloma in the relapsed setting. And as you can see, overall response rates are about 24 percent in a study where patients needed to be refractory to prior therapy. And if you use the drug a little bit earlier, then you get higher response rates, about 40 to 53 percent. In patients that are refractory to Velcade, because it has the same mechanism of action, response rates are lower, in the range of about 17 percent, but we still see some patients that respond. So this is a drug that is effective in myeloma and we are very hopeful that we will have it available for patients at the beginning of August, so in a few months. Slide 35: MLN9708 I talked to you a little bit about MLN9708, which is an oral proteasome inhibitor or oral Velcade. And in the relapse setting also has been tested and is also a drug that is effective, especially when combined with dexamethasone. Slide 36: Marizomib There is another proteasome inhibitor that is called NPI The commercial name will be marizomib. It is an oral drug and also we can see responses in the relapse setting. This drug, the MLN and this drug, are still not in the FDA, so it will be a few years before they are available. Slide 37: HuLuc63/Elotuzumab Elotuzumab is actually an antibody, a monoclonal antibody, against a protein that is preferentially expressed in the myeloma cells. And in combination with Revlimid, has been shown to be very effective with response rates in the 80 percent range, which is very amazing for this patient population. So there are some studies, other studies now ongoing, testing this regimen further. Slide 38: BT062 There s also some monoclonal antibodies against proteins expressed by the myeloma cells. And in one particular study they tested this one that is called BT062. And also there were some responses, and minimal responses, and stabilization of disease in about 50 percent of the patients. 9

10 Slide 39: Vorinostat Vorinostat, you might have heard about this drug. There was a big study done. This drug is the type of drug that usually, in combination with bortezomib, makes the cells more sensitive to bortezomib or Velcade. And it was tested. There was a study done where patients were randomized to receive either bortezomib by itself or bortezomib with the drug. And response rates were 56 percent when used in combination versus 41 percent when used just bortezomib. So this is a drug that by itself is not effective, but when you combine it with bortezomib you can make the Velcade, which is bortezomib, work better against the myeloma cells. Slide 40: Panobinostat And similarly, there is another drug that is called panobinostat, it s the same class of drug. And we actually did a study where we tested this drug in combination with Velcade in patients that were no longer responding to Velcade, where the disease was resistant to Velcade. And the overall response in this group of patients was 30 percent. We really see some very amazing responses. So these new drugs are very exciting because they will actually make the disease again sensitive to drugs that the disease was resistant to prior to that. Slide 41: Perifosine And then perifosine is another drug that can sensitize myeloma cells to bortezomib and dexamethasone. In this study there were 84 patients treated and response rates, more than minimal response, was in the range of about 40 percent. So all these drugs that I mentioned are drugs that are in studies now and they are actually accessible in clinical trials in different institutions in the United States and Europe. Slide 42: Take Home Message(s) So I m going to finish with some take-home messages. Number one, smoldering myeloma is a disease that, these are patients that have myeloma but have no symptoms. I would recommend the patient that has smoldering myeloma consider participating in a clinical trial, but in absence of a clinical trial I would recommend that these patients are observed and followed very closely and treatment deferred until the protein starts to go up and give us an indication that the disease is getting more active. In terms of induction therapy, the optimal choice of induction therapy includes and has to include a novel agent. So things like BAV and probably thalidomide and dexamethasone only are not appropriate induction therapies nowadays. We have to go with either a combination that contains either Revlimid or Velcade or one of these new combinations in clinical trials. The two new drugs, actually I would say three new drugs that are closer I think to getting to the clinic and are effective in myeloma and we are very excited about the results, are carfilzomib, which is a proteasome inhibitor, and then MLN9708, also proteasome inhibitor, and then, of course, pomalidomide, which is lenalidomide derivative. 10

11 11 Slide 43: Take Home Message(s) Lenalidomide post-transplant as maintenance is a good option, but we don t understand very well the risk that it carries in terms of secondary malignancies. So this is something that I don t think every patient should take, but you should discuss with your doctor what are the risks and benefits of receiving this drug. But definitely should be considered and discussed as maintenance therapy after transplant. There are several new drugs that I mentioned to you briefly that are actually offering a very promising strategy to treat myeloma in the relapse-refractory setting. And you should always think about these when you need new therapy, particularly in the relapsed setting. So clinical trial participation should be considered at all times when you re considering treatment for your disease. Slide 44: Acknowledgements So I will end at this point and I just want to remind you that The Leukemia & Lymphoma Society really needs your feedback on this program, so please remember to complete the program evaluation in your packet. And I will hand the speaker phone now to Kathy. Slide 45: Management of Myeloma Symptoms and Side Effects KATHY A. DAILY: Thank you, Dr. Alsina. I m so happy to be here today. Dr. Alsina just spoke to you about current and emerging treatment options for myeloma, and so I will continue with possible myeloma symptoms and management for treatment side effects that impact survivorship for people living with myeloma. Slide 46: Content So first we ll talk about myelosuppression, peripheral neuropathy, deep vein thrombosis, bone pain, fatigue and survivorship. Slide 47: Myelosuppression Multiple myeloma may cause myelosuppression or treatments for myeloma may cause myelosuppression. So myelosuppression means low blood counts, low white blood cells that fight off infections, low red blood cells that carry oxygen throughout the body, and low platelets that help with blood clotting. White blood cells, red blood cells and platelets are measured in a blood test called a CBC. Slide 48: Treatment Related Myelosuppression All of the novel agents used to treat myeloma have various ways of affecting the blood counts. Thalidomide may or may not cause a slight decrease in white blood cells. A CBC should be monitored monthly. Velcade or bortezomib may cause a drop in white blood cells, but especially platelets may decrease. This drop in platelets is temporary. The platelets will be lowest with the last dose of each cycle and will return to normal with the first dose of the next cycle. A CBC should be monitored prior to each cycle of Velcade or as prescribed by your physician.

12 KATHY A. DAILY: Revlimid may cause low white blood cells, red blood cells and platelets. CBCs should be monitored at least monthly or as required by your physician. Single agent in combination chemotherapies may lower white blood cells as well, such as Cytoxan, melphalan, combinations such as CVAD, Cytoxan, vincristine, Adriamycin, dexamethasone, and there are many other combinations of chemotherapies. Steroids such as prednisone and dexamethasone are very powerful and effective in treating myeloma, however, they too may affect the immune system, causing increased susceptibility to infection, even though they do not lower the white blood cells. Slide 49: Low White Blood Cells Neutrophils are part of the white blood cells that fight off bacterial infections. When the neutrophils fall below 1,000, a growth factor called Neupogen, GCSF, has several different names, may be given under the skin to temporarily increase the white blood cells. Slide 50: Infection Prevention Good hand washing is always the number one barrier against preventing infection. However, stay away from crowds if your immune system is suppressed, stay away from people who are sick or coughing. If your white blood cells are low, your doctor may put you on a preventive antibiotic. Don t take Tylenol if you run a fever, call your doctor first. If your doctor is not available, go to the nearest emergency room. Slide 51: Low Platelet Count If the platelets are low, it is easier to bruise. This is the time to be extra cautious not to bump into anything, trip or fall. If you have a nosebleed or new bleeding from your gums, notify your myeloma doctor. You may need a platelet transfusion. Your doctor may stop daily aspirin if your platelets are low, until they return to normal. Slide 52: Low Red Blood Cells If the red cells are low you may experience fatigue. Aranesp or Procrit injections can be given under the skin to increase the red blood cells until you start producing red blood cells on your own. If you are experiencing new shortness of breath with activities that you were previously able to do, for instance, bringing in the groceries or making a bed, you should notify your doctor. This could be an indication the red blood cells are low and a blood transfusion may be needed. Slide 53: Peripheral Neuropathy Peripheral neuropathy is damage to the peripheral nervous system. Multiple myeloma patients may develop peripheral neuropathy from the myeloma or from therapies for treating the myeloma. Neuropathy can be mild to severe. It is described as feelings of numbness, tingling, burning, walking on marbles, and neuropathy may also be described as very painful. 12

13 KATHY A. DAILY: Slide 54: Myeloma Medications Causing Peripheral Neuropathy Thalidomide may cause neuropathy. It s described as numbness in the balls of the feet and tingling in the fingers and toes. Thalidomide neuropathies may not be reversible if left unmanaged, so tell your doctor at the first sign of these symptoms. Velcade neuropathies have many times been described as pain in the feet and legs. Any new pain experienced after starting Velcade or any other treatment should be reported to your myeloma doctor immediately. Velcade neuropathies may be partially or fully reversible. Velcade can even be changed from intravenous to subcutaneous to lessen neuropathy, or changing the dose or the schedule may make a difference in neuropathy as well, so tell your physician. Revlimid or lenalidomide has the lowest incidence of neuropathy of the three novel agents, thalidomide, Velcade and Revlimid. It is actually very rare to experience neuropathy while taking Revlimid. However, it may cause cramping in the hands and feet. Drinking two to three glasses of tonic water a day has been reported by many patients to lessen or eliminate this cramping. It s worth a try. Slide 55: Symptom Management of Peripheral Neuropathy The good news is, if you have symptoms of neuropathy, share them with your doctor or nurse as they occur. Neuropathies do not have to become permanent. We can manage neuropathy much better today than we did yesterday, but we need your help. It s a group effort. Having symptoms of peripheral neuropathy does not necessarily mean stopping your current treatment. Making a schedule change or a dosage change is the number one way to manage peripheral neuropathy while maintaining effective control of the disease. Some topical comfort measures that may lessen the discomfort of peripheral neuropathy are cocoa butter, rubbed into the painful area, Neuragen cream or Reactiv cream, which can be purchased over-the-counter at the drugstore or via the internet; and sometimes a lidocaine patch, which is applied to a specific area for 12 hours every 24 hours. But lidocaine patches must be obtained with a prescription from your doctor. There are many patients who receive benefit from taking B complex vitamins. B1, B6, B12, folic acid, Vitamin E, acetyl L-carnitine and lipoic acid before starting treatments that may cause neuropathies. Or they may lessen existing neuropathies. Prescription medications for relief of discomfort from a neuropathy may include Neurontin or gabapentin, Lyrica or Elavil, and opiates, such as oxycodone, can be used for very painful neuropathy. Slide 56: Deep Vein Thrombosis DVTs or deep vein thrombosis, this is a blood clot. The cause can be the result of having myeloma itself or it can be a side effect of treatment for myeloma. For example, Revlimid plus dexamethasone or thalidomide plus dexamethasone, combination chemotherapies, Epogen, Procrit, these can all cause blood clots, but there are things that we can do. 13

14 KATHY A. DAILY: Slide 57: DVT Prevention Daily aspirin of 81 milligrams, which is a baby aspirin, is recommended while taking any of these therapies to help prevent clots. However, full dose Coumadin or Lovenox may be needed, depending on individual risk factors. For example, if a patient has a history of blood clots, he may need to be fully anticoagulated. Increasing circulation may also aid in preventing clots. Do not stay in any one position for an extended length of time. Get out of the car every one to two hours when taking a road trip. When flying, move around the airplane every hour if allowed. Call your doctor if you notice swelling in only one leg or one arm. The swollen area may or may not be painful. It might be red, it might be warm. It may not be. If your doctor is unavailable go to the nearest hospital or emergency room. Slide 58: Bone Pain Bone pain is a very common symptom of myeloma. Pain can wear you out. It can cause sleep disturbances, delayed healing, a decrease in activity level, leading to depression and stress, with the end result being chronic fatigue. Slide 59: Treatment for Bone Pain Pain related to the myeloma can be managed expertly by your myeloma doctor, not only with combinations of pain medications, radiation therapy and kyphoplasty for painful compression fractures, but imaging and relaxation measures can also help alleviate pain. It s not advisable to lift more than five or ten pounds if your bones have been affected by the myeloma. Slide 60: Side Effects of Bisphosphonates Bisphosphonates such as intravenous Aredia or Zometa, these are bisphosphonates, can be given monthly or every three months to decrease damage to the bones. With bisphosphonates, such as Zometa or Aredia, there are two main points to keep in mind. A blood test called a serum creatinine should be done before each dose of bisphosphonates to test the kidney function. If the serum creatinine is elevated, your doctor may want to adjust the dose. Osteonecrosis of the jaw or ONJ is exposed bone in the oral cavity. While on Zometa or Aredia, there is a risk that exposed bone will not heal. You can be proactive in preventing ONJ or osteonecrosis of the jaw. Before having any invasive dental work, such as tooth extractions or root canals, patients should inform their myeloma doctor. The Zometa should be held at least one month prior to the procedure and should not be restarted until your dentist confirms complete healing of the area. Maintaining good oral hygiene with routine dental exams is important in preventing ONJ while on bisphosphonates. Slide 61: Fatigue and Survivorship Fatigue may be the number one issue affecting the quality of everyday life for survivors of multiple myeloma. The causes of fatigue are multifactorial. Fatigue is interwoven between symptoms related to the myeloma and side effects of treatment for the myeloma. 14

15 KATHY A. DAILY: Slide 62: Factors Contributing to Fatigue and Management Suggestions Decreased activity can certainly add to fatigue. I ve found that the majority of myeloma patients were not typically inactive prior to their diagnosis. Dealing with fatigue may be very frustrating, so balance, balance, balance is the key. You may need to rethink your lifestyle, plan your activities and pace your days. Using up all of your energy on a really good day may result in complete exhaustion for the next two days. Learning to pace oneself with intermittent periods of activity and rest can be helpful in conserving energy throughout the day. Walking and swimming or walking in the pool are the two best exercises for myeloma patients. Not only are you increasing your energy level, but improving circulation, strengthening bones and strengthening muscles, which could be weakened as a side effect of steroids. Activity also increases your serotonin levels in the brain, which will elevate your mood. Dehydration will cause fatigue. And not being well hydrated is very hard on your kidneys. All myeloma patients should be drinking plenty of water every day. Always ask your physician before taking over-the-counter pain medications and also make sure your doctor knows the medications you are already taking, because these medications may affect your kidneys. Have your blood pressure, your blood sugar tested frequently and your kidney serum creatinine checked on a regular basis. Poor nutrition from lack of appetite or taste changes, nausea, diarrhea and depression can definitely make you tired. A well balanced diet with a multivitamin is ideal. Small amounts of nutritious foods throughout the day can be more tolerable than three major meals. Poor nutrition can also be caused from overeating the wrong kinds of foods. People on steroids have an insatiable appetite due to these medications. Keeping healthy snacks on-hand at all times, such as unsalted almonds, carrot and celery sticks, and various fruits, can help cut down on unhealthy snacks, which can lead to weight gain. Most hospitals and cancer facilities have a nutritionist who can help with any type of special diet including renal diets for patients with kidney dysfunction related to the myeloma, or diabetic diets for elevated blood sugars, which may be related to steroids. Treatments and medications may cause fatigue. Only you know how tired you are. Make sure you tell your doctor if you experience increased fatigue after starting a new treatment. A change in dose or schedule of the treatment can make a big difference in how you feel. Go over your list of medications with your doctor to see if there are any adjustments or changes that can be made. Sometimes just a little tweaking can make a big difference in decreasing fatigue and increasing energy. The reasons for sleeplessness are enumerable and whatever the reason, sleep disturbances also cause chronic fatigue. Let your doctor know if you re having trouble getting to sleep or waking in the middle of the night without being able to go back to sleep. There are many medications that are safe and can be given for sleep. However, many times, if the underlying factor is addressed, the sleeplessness resolves. For example, steroids such as dexamethasone and prednisone, which give you energy while taking them, should be taken in the morning. If taken in the evening, they may keep you awake all night. Depression and stress may accompany any cancer diagnosis. Meditation, prayer, relaxation and support groups may be used to decrease stress. If depression persists day after day, you may need a boost to bring joy back into your life. Talking to your doctor about an antidepressant could be a very good idea. 15

16 KATHY A. DAILY: Fatigue is a silent symptom and it requires support, understanding and patience from families, friends and loved ones. Slide 63: Living a Healthy Life with Myeloma Multiple myeloma is manageable. Myeloma patients are living more than twice as long as they did 20 years ago. In order to maintain optimal health, it is very important to get regular checkups from your primary doctor. Regular screenings for blood pressure, cholesterol, thyroid, PSA, mammograms, Pap smears, colonoscopies and skin checks, these should not be neglected. Keeping stress to the minimum and energy to the maximum should be a major goal for myeloma patients. Slide 64: There are Treatments that Work The most important point is doing what works for you. Because today there is more than hope for myeloma patients and their families. There are treatments that work, side effects that are manageable, and research that is promising for tomorrow. Thank you. Slide 65: Question and Answer Session Thank you, Ms. Daily, and also thank you to Dr. Alsina for such an informative presentation today. It is now time for the live question and answer portion of our program. Our first question is from Kathy for Dr. Alsina. What is the name of the blood test used to determine the aggressiveness of the myeloma? So there are two tests. One test is done when they do the bone marrow biopsy. And it s called cytogenetics. It looks at all the different chromosomes in the myeloma cells. And we can also look at that by doing another test that is called FISH. That means fluorescent immunohistochemistry. And it s a more sensitive test to look at the same thing. And also done in the bone marrow. And then the third test that I talked a little bit about is called MyPRS. It s to look at gene expression profile. That is a relatively new test, but actually we ve been doing it more because actually Medicare pays for that and it gives us prognostic information. Great, thank you, Kathy, for submitting your question. Operator, we ll take a question from the telephone audience, please. OPERATOR: Next question comes from Brenda in Virginia. 16

17 BRENDA: Yes, I m interested to find out what the doctor feels about Gammagard. I think you re talking about intravenous immunoglobulins. BRENDA: Yes. Okay, so myeloma patients, as I mentioned before, they are at an increased risk of infections because the cells that cause myeloma are part of your immune system and now they re not working normally. So when patients with myeloma have frequent infections, we consider giving them immunoglobulins, which is an antibody, antibodies. And we do that on a monthly basis. And they have been shown to be helpful in patients, to prevent infections in patients with frequent infections. So we define that by a patient that has three or more respiratory infections in a year, and then we treat those patients. We don t do it for every patient because not all patients actually need this and not all patients benefit from it. But it s effective in that setting. Great, thank you, Brenda, for calling in. Our next question comes from the web and it comes from Brenda. What is complete remission? When IgG is 1490, is that complete remission? Not necessarily. There are two ways of measuring the protein in the blood made by the myeloma cells. One is measuring directly the protein, like the immunoglobulins, like your IgG or your IgA. But we all have those proteins in the blood, so when you measure an IgA, for example, if an IgA is 3000, some of that IgA is going to be normal. So to know exactly what is the part made by the myeloma cells, we do a test that we call serum protein electrophoresis, where all the proteins in the blood are divided. And we can look at something that we call the M spike. M stands for monoclonal, meaning that protein is coming just from one cell that went bad and grew. So that M spike is the way we determine response in myeloma. So for a patient to be in complete remission or have a complete response, that M spike has to be zero, it has to be gone. Someone that has an IgG of 1490, even though it is within normal limits, can still have a small M spike and not be in complete remission. Great, thank you, Brenda, for submitting your question. Operator, we ll take our next question from the telephone audience. OPERATOR: Our next question comes from Margaret in California. 17

18 MARGARET: This is for either Doctor or Nurse. Thank you first of all for everything. I m on Revlimid and dex and I m a survivor since 2005, thank God. I m doing very well on these, except I do get the fatigue. But my question is, which lowers the platelets and the white, is it the dex more or the Revlimid more? And which lowers the blood protein? Again, is it the dex more or is it the Revlimid more? And which damages the good cells as well as the bad cells? Again, those two treatments. Is it good to heal and be off? I m off right now the Revlimid because my platelets are low and my white so I have to balance it, like you say, with the doctor. And I want to know if it s good to be off the dex a while to heal or is it better to stay on that? The doctor recommends I stay on it, but I don t know sometimes, it is very hard on the system. So there you go. KATHY A. DAILY: It s the Revlimid that lowers the white cells and the platelets, it s not the dexamethasone. And if your doctor thinks you need a break from that and the fatigue and the bone marrow need a break from that, then that s probably a pretty good idea, to stay off both of them if that s what he s suggested and get a real break. Thank you, Margaret, for calling in. Our next question comes from the web for Ms. Daily and it comes from Phil. I received initial treatment and transplant. What post-treatment can I receive that won t make my neuropathy worse? KATHY A. DAILY: The Revlimid would be the best choice for not making the neuropathy worse. But sometimes post-transplant maintenance, Velcade given subcutaneously weekly can work as well. But probably the first choice would be Revlimid because it has a rare chance of causing any neuropathy. Great, thank you, Phil. We ll take our next question from the telephone audience, please. OPERATOR: Our next question comes from Rosalee in New Jersey. ROSALEE: If someone is an IgA, and activity shows up in another band, what is this an indication of? So it depends on the setting, but is this after transplant? ROSALEE: No. A long time survivor. 18