Myeloma–Treatment and Side Effects Management...

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Myeloma–Treatment and Side Effects Management Update

Melissa Alsina, MD and Kathy A. Daily, RN, OCNMay 15, 2012

Slide 1: Myeloma–Treatment and Side Effects Management

OPERATOR:Hello, everyone, and welcome to Myeloma–Treatment and Side Effects Management Update, a freetelephone/web education program. It is my pleasure to introduce your moderator Mabel Maia of TheLeukemia & Lymphoma Society.

Slide 2: Welcome and Introduction

MABEL MAIA:Hello, everyone. On behalf of The Leukemia & Lymphoma Society, a warm welcome to all of you and aspecial 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 participantsfrom 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 MultipleMyeloma 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. LeeMoffitt 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 toDr. Alsina.

Slide 3: New Advances in the Treatment of MM

DR. MELISSA ALSINA:Thank you so much for that introduction. I want to thank The Leukemia & Lymphoma Society for organizingthis 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 noveltherapies 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 arecells that we all have. They’re part of our immune system and their normal function is to produce antibodiesor proteins to help us deal with infections. So these cells can grow, in the majority of the cases we don’t knowwhat the cause is, and they grow and then they usually grow inside of the bone marrow and they keepproducing abnormal proteins in very high amounts. These proteins can actually damage the kidneys. Somepatients with myeloma can present with kidney failure. The myeloma cells grow in the bone and they cancause bone destruction, so patients with myeloma frequently can present with what we call bone lesions andbone pain. They don’t let the bone marrow function normally, so patients with myeloma can also present withanemia or low red cell counts. And they can also have a high calcium in the blood because of the bonedestruction.

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Slide 5: Epidemiology It is a relatively rare disease. There were in 2010, there were about 20,000 new cases of myeloma diagnosedin the United States. And it’s about 15 percent of the cancers of the blood. It’s a disease that usually affectsolder people, so the median age of diagnosis is about 70. And 99 percent of the patients are going to beover 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 wedon’t know really the reason for that. And in general it’s not a disease that is hereditary or can be passed infamilies, even though we have seen some clusters in families.

Environmental risks that have been described are pesticides, very significant exposure to pesticides, radiationexposure, Agent Orange, but in general in the majority of the patients we really cannot identify what causesthe 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 asyou can see the majority of the patients are going to be older than 70, as I already mentioned.

Slide 7: DiagnosisPatients with myeloma, in their presentation, usually they will present with anemia or low red cell counts andwhen a patient has anemia the patient will usually be very tired and have fatigue. Bone pain we see probablyin 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 renalfailure. That means kidney disease. And about the same amount will have a high calcium. And because thecells that cause myeloma are part of your immune system, when they’re not working normally, then yourimmune system becomes weak and patients with myeloma frequently present with multiple infections orfrequent infections.

Slide 8: Diagnosis To make a diagnosis of myeloma, the most important test is the bone marrow aspiration and biopsy becausewe have to show that these cancer cells are growing in the bone marrow. But besides that, it’s very importantto look at the blood count, look at the blood to check the calcium, the kidney function. And we also do somevery special protein studies to look at the levels of these proteins. And this is very important becausemeasuring 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 respondingto 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 myelomacells and that is very important in terms of prognosis.

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Slide 9: Skeletal SurveyTypically we do X-rays of the bone to look at all the bones. We call that a skeletal bone survey. And frequentlywe can identify in the bone survey what we call lytic lesions that are like black holes in the bone, indicatingareas 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, wehave 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 ContinuumSo myeloma, once you make the diagnosis of myeloma, which would be made if there is increased plasmacells, these cells in the bone marrow, to more than 10 percent, then we have to decide if the disease is activeor 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 percentplasma cells in the bone marrow. They have increased levels of the protein in the blood. However, they arenot having any symptoms related to the disease. So they do not have hypercalcemia, anemia, kidneyproblems or bone disease.

These patients usually are diagnosed incidentally actually because someone found that maybe they have mildanemia or maybe they have an elevated protein in the blood. And from the information that we have rightnow, patients with smoldering myeloma should be observed, even though at this point there are somestudies ongoing, looking particularly at patients that have smoldering myeloma that we think are at a high riskof progressing quickly. And there’s a question whether those patients need to be treated or not. But in generalsmoldering myeloma should be observed very closely. In contrast to active myeloma, where patients havesymptoms or organ damaged associated with the disease and those patients should start therapy as soon aspossible.

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, alittle 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: StagingFor staging we have two staging systems, the International Staging System that looks at a protein in the bloodthat 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.

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Slide 14: StagingThe Durie-Salmon Staging System is also stage I, II and III and actually gives us information as to whether thepatient has very active myeloma in terms of symptoms, looking at the hemoglobin, at the bones, at theprotein level. A patient that has Durie-Salmon stage I usually does not have any symptoms, has smolderingmyeloma, 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 callcytogenetics and FISH, that we do in the bone marrow and we do the bone marrow and that classifies apatient as having high risk myeloma and standard risk myeloma. Patients with high risk myeloma frequentlyrespond to therapy, but the response is shorter than patients with standard risk. And we still are doingresearch 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 thecancer cells. This is a test that came out recently and we’ve been doing it for prognostic information, but westill don’t know very well how to use this to decide therapy. So it’s a test that we can do for information, butit’s really not going to dictate which therapy a patient should get, at least for now. We hope that in the futurethis test, looking at gene expression profile, will be able to dictate how we treat the individual patient.

Slide 17: Response CriteriaIn myeloma we talk about response, how a patient responds. As I mentioned before, the best way to look atthis is to look at the protein level. And we have categories of response. So you might have heard things likeCR, meaning complete response, or VGPR, which means very good partial response, or PR, which meanspartial response. And these are all categories that have been developed based on the protein levels. So forexample, a partial response would be that there’s more than 50 percent reduction in the protein level. A verygood partial response would mean that there’s over 90 percent reduction in the protein level. And a completeresponse means that the abnormal protein is completely gone. So there’s no abnormal protein in the bloodor in the urine.

Nowadays with the new therapies that we have, we’re actually happy to say that we can get about 70 percentof the patients to be either in a very good partial response or complete remission. And the goal of therapyshould be to get patients in complete remission because we know that patients that can achieve a completeremission or a complete response can live longer and stay longer with the disease under control. And this isespecially 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 wehad the new agents, we were only able to achieve complete remission in about 3 percent of the patients andafter autologous transplantation, in about 30 percent of the patients. And now we’re talking with the newdrugs, 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 helpeddefinitely in the survival and treatment of myeloma.

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Slide 18: Our Growing Agents in MMSo the one slide that I’m showing now has a list of drugs and this is just to give you a general idea of whatare the different classes of drugs that we are now using in myeloma. And we have a number of new drugsthat are proteasome inhibitors like bortezomib or Velcade®. We have drugs that are immunomodulatory drugslike thalidomide and lenalidomide. We have other new drugs and then we still have the traditional agents, theold chemotherapy, which actually works very well in myeloma and we still use it, more commonly in combinationwith a new drug.

Slide 19: Clinical TrialsThe reason why we have all these new drugs in myeloma is because there are clinical trials. So a clinical trialis a research study that involves people. It is a final step in a long process that begins with preliminarylaboratory research and animal testing. So when a drug in the lab or in animal testing is considered to beactive in myeloma, then we take that drug to the clinic. But we have to first make sure, number one, that thedrug is safe to give, and then we need to test the efficacy of the drug. And the only way we can get a drugapproved for clinical use is if the drug has been shown to be safe and effective through a clinical trial. So thereason we have bortezomib or Velcade or Revlimid® available nowadays for myeloma patients is becausehundreds 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 wecan do it in combination with a drug that is already standard to try to improve on the efficacy of that drug, orwe can do it to test a new drug. I think the more people who participate in clinical trials the faster theseresearch questions can be answered and the faster the drugs will go from the laboratory to the clinic. Soagain, very important to participate in a clinical trial. And in myeloma in particular, which is a field that ischanging very quickly and we have learned a lot, but there’s a lot more to learn, it’s actually an essentialcomponent.

Slide 20: Treatment OverviewSo in general the treatment of myeloma, we can divide the treatment of myeloma in three phases. The firstphase is when a patient is initially diagnosed with active myeloma and needs therapy. We call that treatmentinduction therapy. And usually in general nowadays what we do is we do a combination of drugs, which couldbe two drugs or three drugs. Usually that regimen contains a steroid and then one of the new drugs and achemotherapy agent or actually a combination of two new drugs. Probably nowadays the most commonlyused induction regimen is called VRD, which includes Velcade, Revlimid and dexamethasone. And thereported 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. Andusually consolidation would be doing an autologous transplant, which means we give high dose chemotherapyand after collecting stem cells from the patient and then we rescue the bone marrow from the effects of thechemotherapy 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 wegive it in high doses.

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And then usually after transplant, then we consider giving the patient maintenance, which is lower doses oftherapy, to try to keep the disease from getting more active.

Slide 21: Primary Treatment AlgorithmSo 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 basethis decision on comorbidities, for example, there could be a patient that has very significant heart disease orlung disease and we know will not be able to tolerate the high dose chemotherapy, and then that patient isclearly not a transplant candidate. And we would do a combination of therapy like Velcade-Revlimid-dexamethasoneor Velcade-melphalan and prednisone or Cytoxan®-bortezomib-dexamethasone. Or we would do a two-drugcombination. 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 wewould 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, sowe don’t want to use that if we will consider the patient for transplant. Usually we would give the patient, apotential transplant patient, four to six cycles of the induction, the initial therapy. And after we achieve the bestresponse, 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 patientswith just induction therapy, transplant is being challenged. Some people would ask well, if I am already incomplete remission, why do I have to go to a transplant. And we don’t know the precise answer to that, butwhat I can tell you, if a patient has achieved a complete remission, I always give my patients the option ofcollecting stem cells, storing them and then staying on maintenance, and then considering the transplant lateron at time of first relapse. However, if a patient is not in remission or has not had a complete response afterinduction, then I normally would advise my patient to proceed with transplant, to try to get them in completeremission. As we know, patients that achieve a complete remission can live longer and can stay longer withtheir disease under control.

Slide 22: New Agents & Primary Therapies What about new agents for induction therapy? So as I mentioned before, nowadays the most commonregimen that we use is Revlimid, Velcade and dexamethasone. However, some of the new drugs are beingtested 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 actionas Velcade or bortezomib. This drug is not yet approved, but actually will be approved for relapsed myelomaprobably at the end of July. And this drug has been tested in combination with Revlimid and dexamethasonein newly diagnosed myeloma patients.

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Fifty-three newly diagnosed myeloma patients were treated in this study and if you have the slides you cansee 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 verygood partial response and complete remission up front, which is what will actually make us get closer to thecure in myeloma.

Slide 24: MRd: MLN9708–Oral Proteasome InhibitorAnother regimen that has been tested is this new drug that is called MLN9708. This is a drug that is likeVelcade, but instead of being as an injection, it comes as a pill. It’s a drug that is not approved yet, but a studywas done combining this drug with Revlimid and dexamethasone and again the response, overall responserate was 100 percent. So again very active regimen that is now in research.

Slide 25: Treatment OverviewWe’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, startingthree months after transplant, and those studies were randomized. So in other words, three months aftertransplant, patients were randomized to receive either no therapy or receive lenalidomide or Revlimid at lowdoses 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 otherstudy was done in France. And actually both studies show the same results.

Slide 28: Lenalidomide MaintenanceIn the next slide I show time-to-progression, from when the patients were started on therapy. And the patientsthat did not get the drug, the median time-to-progression after transplant was about two years. Whereas themedian time-to-progression in the patients that got lenalidomide had not been reached. So there was adefinitive 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 Americanstudy there was a suggestion that there might be some survival advantage.

Slide 29: Lenalidomide MaintenanceHowever, there is a concern because in the group of patients that received lenalidomide, there was anincreased risk for developing secondary malignancy, secondary cancers. Most commonly cancers were likeleukemia, myelodysplastic syndrome. And as you can see in this slide, there were 25 new cancers among231 patients treated with Revlimid and there were six among 229 patients not treated with the drug. And themedian time that patients developed this was about two years. So it was a little bit early to what we would

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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 abnormalcytogenetic abnormalities in the myeloma cells, or if the patient is not in complete remission, I would advisemy 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 notput 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’ssomething you should discuss with your doctor if you’re going to get lenalidomide post-transplant asmaintenance.

Slide 30: Relapsed/Refractory MMMoving to the relapse-refractory setting, that would mean that a relapsed patient is a patient that receivedinduction therapy, initial therapy, had a response, maybe had a response that was sustained for three yearsand then the disease gets active again. And how do we treat those patients? Well, we have to look at somecharacteristics at that point. Sometimes this relapse, that we call, is just maybe a slight increase in the proteinand the patients have no symptoms. So we have to consider if the relapse is aggressive or not. We have toconsider what treatments the patients have had in the past and what toxicities the patient had, before wedecide on the therapy. And also patient preference. I think in the relapsed setting, in contrast to when you’retreating a newly diagnosed patient, in a newly diagnosed patient, the goal of therapy is to try to get the patientthe best response possible, which would be a complete response or a complete remission. However, in therelapsed setting, the goal of therapy is to try to preserve quality of life. So we want to treat a patient with aregimen that the patient can tolerate well and does not affect the quality of life.

Slide 31: New Agents and TherapiesSo I’m going to talk about the new drugs that we have for the relapsed setting. We obviously can usebortezomib and lenalidomide or Velcade and Revlimid for relapse, but I’ll just mention some of the newdrugs.

Slide 32: PomalidomidePomalidomide is a drug that is a derivative of Revlimid or lenalidomide, it’s a very active drug in myeloma, andthere have been several studies done and overall response rates range from about 25 to 40 percent, as asingle agent or used in combination with dexamethasone. This drug was just submitted to the FDA forapproval, so we expect to have this drug available for patients in the next year or so.

Slide 33: PomalidomidePomalidomide has also been tested in combination with other agents and if you combine these drugs, youget actually better response rates. So a response rate of 30 percent when you use the drug by itself, or withdexamethasone, when you add another agent like Cytoxan, you can get response rates about 60 percent.

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And the good news is that even though this drug is a derivative of Revlimid, it’s effective even in patients thatare 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, anddexamethasone.

Slide 34: CarfilzomibI’ll just talk a little bit about carfilzomib, which is the new drug that will be probably approved by the FDA atthe end of July. And this slide shows the two biggest studies that have been done in myeloma in the relapsedsetting. And as you can see, overall response rates are about 24 percent in a study where patients needed tobe 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 arelower, 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 patientsat the beginning of August, so in a few months.

Slide 35: MLN9708I talked to you a little bit about MLN9708, which is an oral proteasome inhibitor or oral Velcade. And in therelapse setting also has been tested and is also a drug that is effective, especially when combined withdexamethasone.

Slide 36: MarizomibThere is another proteasome inhibitor that is called NPI-0052. The commercial name will be marizomib. It isan oral drug and also we can see responses in the relapse setting. This drug, the MLN and this drug, are stillnot in the FDA, so it will be a few years before they are available.

Slide 37: HuLuc63/ElotuzumabElotuzumab is actually an antibody, a monoclonal antibody, against a protein that is preferentially expressed inthe myeloma cells. And in combination with Revlimid, has been shown to be very effective with responserates 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: BT062There’s also some monoclonal antibodies against proteins expressed by the myeloma cells. And in oneparticular study they tested this one that is called BT062. And also there were some responses, and minimalresponses, and stabilization of disease in about 50 percent of the patients.

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Slide 39: VorinostatVorinostat, you might have heard about this drug. There was a big study done. This drug is the type of drugthat usually, in combination with bortezomib, makes the cells more sensitive to bortezomib or Velcade. And itwas tested. There was a study done where patients were randomized to receive either bortezomib by itself orbortezomib with the drug. And response rates were 56 percent when used in combination versus 41 percentwhen used just bortezomib. So this is a drug that by itself is not effective, but when you combine it withbortezomib you can make the Velcade, which is bortezomib, work better against the myeloma cells.

Slide 40: PanobinostatAnd similarly, there is another drug that is called panobinostat, it’s the same class of drug. And we actually dida study where we tested this drug in combination with Velcade in patients that were no longer responding toVelcade, where the disease was resistant to Velcade. And the overall response in this group of patients was 30percent. 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 thatthe disease was resistant to prior to that.

Slide 41: PerifosineAnd then perifosine is another drug that can sensitize myeloma cells to bortezomib and dexamethasone. Inthis study there were 84 patients treated and response rates, more than minimal response, was in the rangeof about 40 percent.

So all these drugs that I mentioned are drugs that are in studies now and they are actually accessible inclinical 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 nosymptoms. I would recommend the patient that has smoldering myeloma consider participating in a clinicaltrial, but in absence of a clinical trial I would recommend that these patients are observed and followed veryclosely and treatment deferred until the protein starts to go up and give us an indication that the disease isgetting more active.

In terms of induction therapy, the optimal choice of induction therapy includes and has to include a novelagent. So things like BAV and probably thalidomide and dexamethasone only are not appropriate inductiontherapies nowadays. We have to go with either a combination that contains either Revlimid or Velcade or oneof 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 areeffective in myeloma and we are very excited about the results, are carfilzomib, which is a proteasomeinhibitor, and then MLN9708, also proteasome inhibitor, and then, of course, pomalidomide, which islenalidomide derivative.

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Slide 43: Take Home Message(s)Lenalidomide post-transplant as maintenance is a good option, but we don’t understand very well the risk thatit 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 definitelyshould 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 strategyto treat myeloma in the relapse-refractory setting. And you should always think about these when you neednew therapy, particularly in the relapsed setting.

So clinical trial participation should be considered at all times when you’re considering treatment for yourdisease.

Slide 44: AcknowledgementsSo I will end at this point and I just want to remind you that The Leukemia & Lymphoma Society really needsyour feedback on this program, so please remember to complete the program evaluation in your packet. AndI 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 emergingtreatment options for myeloma, and so I will continue with possible myeloma symptoms and managementfor treatment side effects that impact survivorship for people living with myeloma.

Slide 46: ContentSo first we’ll talk about myelosuppression, peripheral neuropathy, deep vein thrombosis, bone pain, fatigueand survivorship.

Slide 47: MyelosuppressionMultiple myeloma may cause myelosuppression or treatments for myeloma may cause myelosuppression. Somyelosuppression means low blood counts, low white blood cells that fight off infections, low red blood cellsthat carry oxygen throughout the body, and low platelets that help with blood clotting. White blood cells, redblood cells and platelets are measured in a blood test called a CBC.

Slide 48: Treatment Related MyelosuppressionAll 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 monitoredmonthly. 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 returnto normal with the first dose of the next cycle. A CBC should be monitored prior to each cycle of Velcade oras prescribed by your physician.

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Revlimid may cause low white blood cells, red blood cells and platelets. CBCs should be monitored at leastmonthly 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 othercombinations 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 thoughthey do not lower the white blood cells.

Slide 49: Low White Blood CellsNeutrophils are part of the white blood cells that fight off bacterial infections. When the neutrophils fall below1,000, a growth factor called Neupogen®, GCSF, has several different names, may be given under the skin totemporarily increase the white blood cells.

Slide 50: Infection PreventionGood hand washing is always the number one barrier against preventing infection. However, stay away fromcrowds if your immune system is suppressed, stay away from people who are sick or coughing. If your whiteblood 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 mayneed a platelet transfusion. Your doctor may stop daily aspirin if your platelets are low, until they return tonormal.

Slide 52: Low Red Blood CellsIf the red cells are low you may experience fatigue. Aranesp® or Procrit® injections can be given under the skinto 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, forinstance, bringing in the groceries or making a bed, you should notify your doctor. This could be an indicationthe red blood cells are low and a blood transfusion may be needed.

Slide 53: Peripheral NeuropathyPeripheral neuropathy is damage to the peripheral nervous system. Multiple myeloma patients may developperipheral neuropathy from the myeloma or from therapies for treating the myeloma. Neuropathy can be mildto severe. It is described as feelings of numbness, tingling, burning, walking on marbles, and neuropathy mayalso be described as very painful.

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Slide 54: Myeloma Medications Causing Peripheral NeuropathyThalidomide may cause neuropathy. It’s described as numbness in the balls of the feet and tingling in thefingers and toes. Thalidomide neuropathies may not be reversible if left unmanaged, so tell your doctor at thefirst sign of these symptoms.

Velcade neuropathies have many times been described as pain in the feet and legs. Any new painexperienced after starting Velcade or any other treatment should be reported to your myeloma doctorimmediately. Velcade neuropathies may be partially or fully reversible. Velcade can even be changed fromintravenous to subcutaneous to lessen neuropathy, or changing the dose or the schedule may make adifference 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 maycause cramping in the hands and feet. Drinking two to three glasses of tonic water a day has been reportedby 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 wedid yesterday, but we need your help. It’s a group effort. Having symptoms of peripheral neuropathy does notnecessarily mean stopping your current treatment. Making a schedule change or a dosage change is thenumber 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 atthe drugstore or via the internet; and sometimes a lidocaine patch, which is applied to a specific area for 12hours 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, VitaminE, acetyl L-carnitine and lipoic acid before starting treatments that may cause neuropathies. Or they maylessen 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 ThrombosisDVTs or deep vein thrombosis, this is a blood clot. The cause can be the result of having myeloma itself or itcan be a side effect of treatment for myeloma. For example, Revlimid plus dexamethasone or thalidomideplus dexamethasone, combination chemotherapies, Epogen®, Procrit, these can all cause blood clots, but thereare things that we can do.

KATHY A. DAILY:

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Slide 57: DVT PreventionDaily aspirin of 81 milligrams, which is a baby aspirin, is recommended while taking any of these therapies tohelp prevent clots. However, full dose Coumadin® or Lovenox® may be needed, depending on individual riskfactors. 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 lengthof time. Get out of the car every one to two hours when taking a road trip. When flying, move around theairplane every hour if allowed. Call your doctor if you notice swelling in only one leg or one arm. The swollenarea may or may not be painful. It might be red, it might be warm. It may not be. If your doctor is unavailablego to the nearest hospital or emergency room.

Slide 58: Bone PainBone 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 beingchronic fatigue.

Slide 59: Treatment for Bone PainPain related to the myeloma can be managed expertly by your myeloma doctor, not only with combinationsof pain medications, radiation therapy and kyphoplasty for painful compression fractures, but imaging andrelaxation 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 BisphosphonatesBisphosphonates such as intravenous Aredia® or Zometa®, these are bisphosphonates, can be given monthlyor 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 beforeeach dose of bisphosphonates to test the kidney function. If the serum creatinine is elevated, your doctor maywant to adjust the dose. Osteonecrosis of the jaw or ONJ is exposed bone in the oral cavity. While on Zometaor Aredia, there is a risk that exposed bone will not heal. You can be proactive in preventing ONJ orosteonecrosis 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 theprocedure and should not be restarted until your dentist confirms complete healing of the area. Maintaininggood oral hygiene with routine dental exams is important in preventing ONJ while on bisphosphonates.

Slide 61: Fatigue and SurvivorshipFatigue 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 andside effects of treatment for the myeloma.

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Slide 62: Factors Contributing to Fatigue and Management SuggestionsDecreased activity can certainly add to fatigue. I’ve found that the majority of myeloma patients were nottypically 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 allof your energy on a really good day may result in complete exhaustion for the next two days. Learning topace oneself with intermittent periods of activity and rest can be helpful in conserving energy throughout theday. Walking and swimming or walking in the pool are the two best exercises for myeloma patients. Not onlyare you increasing your energy level, but improving circulation, strengthening bones and strengtheningmuscles, which could be weakened as a side effect of steroids. Activity also increases your serotonin levels inthe brain, which will elevate your mood.

Dehydration will cause fatigue. And not being well hydrated is very hard on your kidneys. All myeloma patientsshould be drinking plenty of water every day. Always ask your physician before taking over-the-counter painmedications and also make sure your doctor knows the medications you are already taking, because thesemedications may affect your kidneys. Have your blood pressure, your blood sugar tested frequently and yourkidney serum creatinine checked on a regular basis.

Poor nutrition from lack of appetite or taste changes, nausea, diarrhea and depression can definitely make youtired. A well balanced diet with a multivitamin is ideal. Small amounts of nutritious foods throughout the daycan be more tolerable than three major meals. Poor nutrition can also be caused from overeating the wrongkinds of foods. People on steroids have an insatiable appetite due to these medications. Keeping healthysnacks on-hand at all times, such as unsalted almonds, carrot and celery sticks, and various fruits, can help cutdown on unhealthy snacks, which can lead to weight gain. Most hospitals and cancer facilities have anutritionist who can help with any type of special diet including renal diets for patients with kidney dysfunctionrelated 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 yourdoctor if you experience increased fatigue after starting a new treatment. A change in dose or schedule of thetreatment can make a big difference in how you feel. Go over your list of medications with your doctor to seeif there are any adjustments or changes that can be made. Sometimes just a little tweaking can make a bigdifference in decreasing fatigue and increasing energy.

The reasons for sleeplessness are enumerable and whatever the reason, sleep disturbances also causechronic fatigue. Let your doctor know if you’re having trouble getting to sleep or waking in the middle of thenight without being able to go back to sleep. There are many medications that are safe and can be given forsleep. 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 takenin 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 supportgroups may be used to decrease stress. If depression persists day after day, you may need a boost to bringjoy back into your life. Talking to your doctor about an antidepressant could be a very good idea.

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Fatigue is a silent symptom and it requires support, understanding and patience from families, friends andloved 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 yearsago. 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, colonoscopiesand skin checks, these should not be neglected. Keeping stress to the minimum and energy to the maximumshould 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 myelomapatients and their families. There are treatments that work, side effects that are manageable, and research thatis promising for tomorrow.

Thank you.

Slide 65: Question and Answer Session

MABEL MAIA: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.

MABEL MAIA:Our first question is from Kathy for Dr. Alsina. What is the name of the blood test used to determine theaggressiveness of the myeloma?

DR. MELISSA ALSINA: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 anothertest that is called FISH. That means fluorescent immunohistochemistry. And it’s a more sensitive test to lookat the same thing. And also done in the bone marrow. And then the third test that I talked a little bit about iscalled MyPRS. It’s to look at gene expression profile. That is a relatively new test, but actually we’ve beendoing it more because actually Medicare pays for that and it gives us prognostic information.

MABEL MAIA:Great, thank you, Kathy, for submitting your question. Operator, we’ll take a question from the telephoneaudience, please.

OPERATOR:Next question comes from Brenda in Virginia.

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BRENDA:Yes, I’m interested to find out what the doctor feels about Gammagard®.

DR. MELISSA ALSINA:I think you’re talking about intravenous immunoglobulins.

BRENDA:Yes.

DR. MELISSA ALSINA:Okay, so myeloma patients, as I mentioned before, they are at an increased risk of infections because thecells that cause myeloma are part of your immune system and now they’re not working normally. So whenpatients with myeloma have frequent infections, we consider giving them immunoglobulins, which is anantibody, 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 ormore respiratory infections in a year, and then we treat those patients. We don’t do it for every patientbecause not all patients actually need this and not all patients benefit from it. But it’s effective in that setting.

MABEL MAIA: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?

DR. MELISSA ALSINA:Not necessarily. There are two ways of measuring the protein in the blood made by the myeloma cells. Oneis measuring directly the protein, like the immunoglobulins, like your IgG or your IgA. But we all have thoseproteins in the blood, so when you measure an IgA, for example, if an IgA is 3000, some of that IgA is goingto be normal. So to know exactly what is the part made by the myeloma cells, we do a test that we callserum protein electrophoresis, where all the proteins in the blood are divided. And we can look at somethingthat we call the M spike. M stands for monoclonal, meaning that protein is coming just from one cell thatwent bad and grew. So that M spike is the way we determine response in myeloma. So for a patient to be incomplete remission or have a complete response, that M spike has to be zero, it has to be gone. Someonethat has an IgG of 1490, even though it is within normal limits, can still have a small M spike and not be incomplete remission.

MABEL MAIA:Great, thank you, Brenda, for submitting your question. Operator, we’ll take our next question from thetelephone audience.

OPERATOR:Our next question comes from Margaret in California.

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MARGARET:This is for either Doctor or Nurse. Thank you first of all for everything. I’m on Revlimid and dex and I’m asurvivor 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 theblood protein? Again, is it the dex more or is it the Revlimid more? And which damages the good cells as wellas the bad cells? Again, those two treatments. Is it good to heal and be off? I’m off right now the Revlimidbecause my platelets are low and my white – so I have to balance it, like you say, with the doctor. And I wantto 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 Istay 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 doctorthinks you need a break from that and the fatigue and the bone marrow need a break from that, then that’sprobably a pretty good idea, to stay off both of them if that’s what he’s suggested and get a real break.

MABEL MAIA:Thank you, Margaret, for calling in. Our next question comes from the web for Ms. Daily and it comes fromPhil. I received initial treatment and transplant. What post-treatment can I receive that won’t make myneuropathy worse?

KATHY A. DAILY:The Revlimid would be the best choice for not making the neuropathy worse. But sometimes post-transplantmaintenance, Velcade given subcutaneously weekly can work as well. But probably the first choice would beRevlimid because it has a rare chance of causing any neuropathy.

MABEL MAIA: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?

DR. MELISSA ALSINA:So it depends on the setting, but is this after transplant?

ROSALEE:No. A long time survivor.

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DR. MELISSA ALSINA:Sometimes someone has, for example, IgA myeloma or maybe IgA-lambda myeloma, and then doesn’t haveany monoclonal spike and you start seeing another monoclonal spike with a different protein in the absenceof any symptoms and so on. And we call that a switch of immunoglobulin. And actually usually in myeloma,especially after transplant, has been shown to confer a better prognosis. And it doesn’t mean that the patientis out of remission. So I think it has to be seen in what context and evaluated, but it’s not necessarily a badthing.

MABEL MAIA:Thank you, Rosalee, for calling in. Our next question is from the web and it comes from Grace. I am 72 yearsold and was diagnosed in 2002 with multiple myeloma, smoldering until 2007. Because of age and otherchronic medical issues, I was advised not to treat. Since I am not being treated, I want to know how often Ishould be doing a 24 hour urine test, what other sorts of tests I should be doing and how frequent do yourecommend them?

DR. MELISSA ALSINA:So I think in very general terms, this can vary from patient to patient, but a patient with smoldering myeloma,we do all the tests every three months. Those tests should include a blood count, CBC, chemistry of theblood to look at the kidneys, the liver, the calcium, quantitative immunoglobulins, serum protein electrophoresisto look at the M spike, 24 hour urine collection for total protein and urine protein electrophoresis to look atthe protein in the urine and also at the M spike in the urine and also serum free light chain. And we normallywould do those every three months. And then we do the bone survey, the complete X-rays of the bonesevery year, once a year, or before if the patient has any symptoms.

MABEL MAIA:Thank you, Grace, for submitting your question. Operator, we’ll take our next question from the telephoneaudience, please.

OPERATOR:Our next question comes from Patricia in Virginia.

PATRICIA:This is for Daily. If you are on intravenous or series of Velcade and you come off of that and start getting itsubcutaneously, can you go back to the IV if you seem to be experiencing more problems than you was whenyou was on the IV?

DR. MELISSA ALSINA:Yes, absolutely, you can go back to the IV if you’re having more problems with the subcutaneous, absolutely, yes.

MABEL MAIA:Thank you, Patricia, for calling in. We’ll take our next question from the web and it comes from Gerald. Whatcan be done to control bone pain?

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KATHY A. DAILY:Bone pain can be controlled in several ways. Of course, there’s always pain medication, there’s narcotics. Ifthere’s compression fractures, painful compression fractures, can successfully be controlled with kyphoplasty,which is a very simple surgical procedure that can be done. Those are a couple of really good ways.Sometimes radiation therapy helps. Relaxation techniques can help. And I think activity can help with bonepain as well, gentle activity, gentle walking, gentle swimming. And bisphosphonates are very good for bonepain, too, to help decrease any further damage to the bones.

MABEL MAIA:Thank you, Gerald, for submitting your question. Operator, we’ll take our next question from the telephoneaudience, please.

OPERATOR:Our next question comes from Edna in North Carolina.

EDNA:I had a stem cell transplant in December, 2010 and everything was going good. But after having severalrespiratory infections, my taste and my smell have gone. And I was wondering if any of your other patientshave experienced that and if so, what did they do?

DR. MELISSA ALSINA:Yes, it’s a relatively common side effect of the chemotherapy, when you get the chemotherapy in high doses.In the majority of the patients, though, it gets better with time. Unfortunately if it is persistent, if it persists,there’s really not a whole lot that one can do to bring that back.

KATHY A. DAILY:I do have one suggestion that might be helpful. You might want to try something very, very sour or very, verysweet, something extreme, to get your tastebuds going again. For instance, if you suck on lemon drops,sometimes that can just get your tastebuds going again, just stimulate them, because it’s so very sour. Orsomething along that line. Sucking on a lemon or a lime to get those tastes going again. So that would beone suggestion. And those might not be the only foods. You might think of some others that might be moreideal for you. But something very extreme.

MABEL MAIA:Great. Thank you, Edna, for calling in. Our next question comes from the web. It comes from Eric. Can youexplain how the data is collected for more information about second cancers and Revlimid?

DR. MELISSA ALSINA:Yeah, these were two studies that were done where all the side effects or events associated to the treatmentare recorded in a very systematic way because these patients all participated in the study. So that’s where thatdata came from. When the patients are treated in a clinical trial, then we get that information. But when the

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patients are not treated in a clinical trial, then it’s much harder to capture that information. So it could be amore common phenomenon, we just don’t know. The studies that used Revlimid in another setting, not post-transplant, but in the relapse setting, where the data was reexamined and there was no increase in secondarymalignancies in those studies. So I think it has something to do with the melphalan, giving the high dosechemotherapy in the transplant, followed by the Revlimid.

MABEL MAIA:Thank you, Eric, for submitting your question. Operator, we’ll take another question from the telephoneaudience, please.

OPERATOR:Our next question comes from Sherry in Maryland.

SHERRY:Yes, thank you. Could you say what the research shows about the role of Zometa or other bisphosphonatesin sustaining remission in the situation where there’s a complete remission, in lengthening the period ofremission?

DR. MELISSA ALSINA:There’s actually only one study that is a randomized study done by the English myeloma group and theytreated patients up front with either Zometa or an oral bisphosphonate that they use in Europe that is calledclodronate. And it was actually patients were treated with Zometa independently regardless of whether theyhad bone disease or not as long as they had active myeloma and required therapy. And the group thatreceived Zometa had a survival advantage, they live longer. So this is, even though there have been manysuggestions that Zometa or bisphosphonates can not only affect the bone, it can also affect the survival of themyeloma cell. This is the first study that shows in a clinical trial that shows this advantage. So that’s theinformation that we have. And that is changing a little bit, I mean the thought about whether patients withoutbone disease should get Zometa, and it’s also changing the thought about how long you should keep apatient on therapy. I mean the guidelines so far say patients should stay on bisphosphonates for two years,but I think if a patient is doing well with a treatment and has no side effects, I would continue my patient ontherapy and just change the frequency to try to avoid toxicity.

MABEL MAIA:Thank you, Sherry, for calling in with your question. We’ll take our next question from the web. Is it possibleright now for any patient to get the myeloma vaccination? If so, how? If not, when will it be available?

DR. MELISSA ALSINA:Myeloma vaccination? I’m not sure that I understand the question. But if they’re referring to vaccines in termsof for treatment against the myeloma, that has been studied and they really have not been shown to be veryeffective. But there are still some studies going on of vaccines against particular proteins that are expressed in

DR. MELISSA ALSINA:

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the myeloma cells. But research in that area has been somewhat disappointing. So we don’t have anything atthis point that I can say well, this is an effective therapy for myeloma.

MABEL MAIA:Thank you. Operator, we’ll take our next question from the telephone audience, please.

OPERATOR:Our next question comes from Deborah in New Mexico.

DEBORAH:What supplements and vitamins? I just had a stem cell transplant. Prior to that I had weekly chemotherapy.What supplements would you consider safe to take? I’m going to see my doctor soon and see what shethinks, if I’m in complete remission. Before I asked her, last time, she said we don’t want you to take anysupplements or vitamins right now. The fear was some of the chemo that might still be in your system. It’sbeen about a month and a half since the stem cell transplant. Can you advise? You spoke about B1, B6 andB12 and maybe a baby aspirin. And also after some time now, if she says I’m in complete remission, whattypes of medicine is given for someone in complete remission? Is it definitely a little small amount of Revlimidor am I completely off any therapeutic drugs for a while until they test the blood and see that it’s out ofwhack again.

DR. MELISSA ALSINA:That’s something you have to discuss with your doctor, but as I mentioned, there are two studies that showthat patients that get low dose Revlimid after transplant stay longer with their disease under control than ifthey don’t take it. However, with the increased risk of secondary malignancies, you have to discuss with yourdoctor so that you can weigh the risks and the benefits. What I do in my practice, if a patient has high riskmyeloma, I do give them maintenance, regardless of whether they are in remission or not. If they havestandard risk myeloma and they are in remission, I do not give them maintenance. However, if they’re not inremission, regardless of high risk or standard risk, then I put them on Revlimid maintenance. It is a discussionthat you need to have with your doctor because your doctor would know how aggressive your disease was,etc., and what are the characteristics of your disease.

And your other question was about vitamins? Really after transplant we just tell the patients to just take amultivitamin, just a regular multivitamin will be enough.

MABEL MAIA:Thank you, Deborah, for calling in. Our next question comes from Gary. With all the new chemotherapiesavailable, is the stem cell transplant still a necessary step in the treatment strategy? Do you feel a person gainsby having a stem cell transplant at some point in the process?

DR. MELISSA ALSINA:

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DR. MELISSA ALSINA:I do. I think patients do get benefit from transplant and the question at this point I think is not whether apatient should have a transplant, but the timing, when. We have a number of treatments in myeloma andtransplant is just one of them. And we just need to try to sequence these treatments in the best way. Ingeneral the studies that have been done recently with the new drugs, followed by transplant, actually withthose, with that combination, we get the best results. So I think patients should definitely consider that option.

There’s a big study that is an international study, that is being done right now, that is comparing Revlimid,Velcade and dexamethasone – this is for newly diagnosed myeloma patients – and then after four cycles,half of the patients go and get a transplant at that point and then maintenance, and then half of the patientscontinue Revlimid, Velcade and dexamethasone and don’t get the transplant at that point. But when thedisease gets active later, they get the transplant. So this study is not going to answer the question whether it’sbest to have a transplant or not in the era of the new drugs, but it’s going to answer the question when it’sbest to have a transplant. If after a few months of induction therapy or later on at first relapse.

And the reason it was developed like that is because myeloma investigators across the world feel that transplantis important and has a role. And again the question is timing, the timing.

What I do in my practice, the way I try to see it, I want to get my patients in complete remission. That’s whereI want to get. If I’m there with the novel drugs, with an induction therapy without a transplant, I would feelcomfortable saying okay, we can collect stem cells, store them, keep you on maintenance and wait and seehow much time we can get just from this therapy. But if a patient is not in remission after induction therapy,then I would like to proceed with transplant because I want to get that patient into remission.

MABEL MAIA:Thank you, Gary, for submitting your question. Operator, we’ll take another question from the telephoneaudience, please.

OPERATOR:Our next question comes from John in North Carolina.

JOHN:Tell me the difference, please, I’ve got non-secretory myeloma. Can you tell me the difference as far asaggressiveness in that kind of disease? And also the thought about Zometa, which I’m getting once a month,I had transplant a year ago, I’m getting Zometa once a month, can I deduct from that that it may also heal thedeteriorated bones that were damaged from myeloma?

DR. MELISSA ALSINA:So the second question regarding the bisphosphonates, the bisphosphonates, what they do is they preventnew bone destruction. They do not induce bone formation. So the damage that is already done in the bonesfrom the myeloma, the bisphosphonates are not going to change. And that damage usually remains. And onlytime can fix that. In a patient, for example, that is in remission for a long time, we can see that some of thosedamaged areas in the bones start to fill up and there’s new bone formation and there’s healing.

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And the first question regarding non-secretory myeloma, non-secretory myeloma is myeloma where we seethe increased number of plasma cells in the bone marrow, but we cannot measure any proteins in the bloodor in the urine. However, there’s a relatively new test that is called serum free light chain that is a verysensitive test to measure these abnormal proteins in the blood. And after this test was developed andestablished, we learned that the majority of the patients that we call non-secretory were patients that reallyhad light chain myeloma, but the protein was not secreted in high enough amounts that we could measureit in the urine. But now with that new test, serum free light chain, we can measure the protein and we canfollow the patient with those proteins.

Non-secretory myeloma is not more aggressive than myeloma that is producing proteins. And the challenge isbeing able to measure, evaluate the response or if the patient is progressing. But again, with the serum freelight chain, now that is a little bit easier. And we do not have to rely only on the bone marrow to follow thesepatients like we needed to do in the past.

MABEL MAIA:Great, thank you for calling in, John. Our next question comes from the web from Camilla. What’s the criteriaof myeloma being found in family members, children or siblings?

DR. MELISSA ALSINA:So this is very rare. So myeloma is considered a disease that is non-hereditary. So really there should not beany significant concerns. There have been some clusters reported in families. I’ve had a sister and a brotheror a mom and a daughter. But this is very, very, very rare. And when we see these, probably we think moreabout the fact that maybe they grew up in a place where they were exposed to something or they wereexposed to the same trigger. But it’s not considered a hereditary disease. Having myeloma doesn’t make yourchildren, for example, at a higher risk of having myeloma, or your siblings or your parents.

MABEL MAIA:Great, thank you. Operator, we’ll take our next question from the telephone audience, please.

OPERATOR:Our next question comes from Joanne in California.

JOANNE:I’m in remission for five years, had a stem cell transplant, but my kidneys were damaged. So I’m on dialysisthree times a week and having more trouble with dialysis and actually on no maintenance for the myeloma.Dialysis is wiping me out. Any good signs there? Thank you.

DR. MELISSA ALSINA:Well, unfortunately if you have been on dialysis for that long, your kidneys are not going to recover. Patientslike you should consider if possible a kidney transplant. In the past this was unheard of because myelomawas a lethal disease and patients would relapse very shortly, there were no good treatments. But nowadays

DR. MELISSA ALSINA:

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that myeloma is a very treatable disease and someone that has been in remission for five years, a transplantdefinitely should be considered if you’re eligible. So a kidney transplant should not be contraindicated justbased on the fact that you had myeloma. And I’ve had several patients actually that have the same problemas you have and have received a kidney transplant. Even if your myeloma at some point becomes active inthe future, there are many good treatments, it’s very likely that kidney failure can be prevented in the future.So I would, if otherwise you are eligible, I would definitely, if I was you, I would try to evaluate the possibilityof getting a kidney transplant.

MABEL MAIA:Joanne, thank you for calling in. Our next question comes from Pamela from the web. What drugs are usedwith bone marrow transplant and will my hair fall out? I am presently taking Velcade and have had no hair loss.

DR. MELISSA ALSINA:Yeah, usually Velcade or Revlimid, the new drugs, do not make the hair fall. But the chemotherapy that weuse for transplant is a drug that is called melphalan and definitely given in high doses will make your hair fall.However, about two to three months after that, your hair will grow back. And the majority of patients, actuallythe hair grows back curly, like stronger, so you get a perm for free. Patients actually like it, they get more hairand more curly and so on. But yes, it is something that unfortunately we cannot avoid, the fact that the haircomes off with chemotherapy.

MABEL MAIA:Thank you, Pamela, for submitting your question. Operator, we’ll take another question from the telephoneaudience, please.

OPERATOR:Our next question comes from Elizabeth in Michigan.

ELIZABETH:I was wondering how common it is if you had a complete remission after a bone marrow transplant, howcommon is it to go into a relapse?

DR. MELISSA ALSINA:Well, in general, I guess in very general terms, we would still say that myeloma remains to be a disease thatis incurable. So the majority of the patients after a transplant will relapse and will require some therapy.However, things are changing. And we have more patients, a lot more patients than before that get inremission, and we are sure that the number of patients that are going to stay free of disease for a long timeis going to increase. We unfortunately don’t have those numbers yet because this is all so new, that we don’tknow. I cannot tell one of my patients, this is your possibility of being in remission ten years from now, I don’tknow. But I suspect that it’s going to increase. And it’s increasing as we speak. There are some studies thathave shown that if a patient is in remission after transplant for more than three years, that those are the

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patients that are going to stay in remission long-term. So I usually tell my patients, we pass that three yearline, that three year mark, I feel that those patients could be the ones that can have long-term benefit.

MABEL MAIA:Great, thank you, Elizabeth, for calling in with your question. Our next question is from the web. It comes fromLaura. Any idea on what triggers relapse after a patient has been in complete remission?

DR. MELISSA ALSINA:No, unfortunately, we don’t know that. In general the reason why we cannot cure myeloma yet is that thosecells are resistant to therapy. So even though a patient is in remission, there could still be some cells that wejust cannot see by the normal ways we have to measure the disease. And then they stay there, they’reresistant to therapy and then eventually they grow. But unfortunately we don’t know what causes that andthere are a lot of studies going on, looking at what are the mechanisms of drug resistance and how to affectthe drug resistance, so that more cells become sensitive and we can actually cure the disease.

Slide 66: LLS Resources

MABEL MAIA:Thank you, Laura, for submitting your question. And actually thank you all for all your questions by phone andby web. Our program has come to a close. Please help me thank Dr. Alsina and Ms. Daily for donating theirtime with us today.

We hope many of your questions were answered and that the information will assist you in your next steps.If we were not able to get to your question or we can provide additional information or support, please callan LLS Information Specialist toll-free at 1-800-955-4572. You can also email us at [email protected].

On behalf of The Leukemia & Lymphoma Society, thank you for sharing your time with us today. Good-byeand we wish you well.

END

DR. MELISSA ALSINA:

Myeloma–Treatment and Side Effects Management...

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