Full Show: Ask the Myeloma Experts – Patient Questions from the St. Louis Myeloma Crowd Round Table Meeting

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multiple myeloma

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Ask the Myeloma Experts
Myeloma Crowd Round Table in St. Louis
December 30, 2016

Summary
It’s a rare opportunity to have a panel of myeloma experts available to answer any patient question that may be asked. Experts at our Myeloma Crowd Round Tables answered common patient questions at our meeting in St. Louis. Listen in to learn more about a wide variety of topics with experts who have over 80 years treating myeloma including: Guido Tricot, MD, PhD (University of Iowa), Morie Gertz, MD (Mayo Clinic), Keith Stockerl-Goldstein, MD (Washington University), and Ravi Vij, MD (Washington University).

Thanks to our Myeloma Crowd Round Table sponsors: Takeda Oncology, Amgen and Signal Genetics
multiple myeloma

 

 

 

Full Transcript
Thank you for joining us on today’s show on Myeloma Crowd Radio. I’m your host, Jenny Ahlstrom.

We’d like to thank Takeda Oncology for their support of this episode.

Today’s show is unique. We’ve been holding Myeloma Crowd Round Tables around the country and plan on hosting more meetings next year. We are very grateful to Takeda Oncology, Amgen and Signal Genetics for sponsoring these key meetings for myeloma patients.

At these meetings we invite myeloma experts to talk about relapsed myeloma, high-risk myeloma, new approaches being used in the clinic and also a doctor or facility’s unique approaches to tackle myeloma using a variety of methods.

Each meeting has sessions where each of the experts discuss a particular topic, like immunotherapy, nanotechnology or high-risk myeloma. During the day, we reserve plenty of time for two sessions of questions and answers. This is one of everybody’s favorite part of the meeting where audience members can ask general questions of the panel of experts in attendance. While the questions are not meant to be personalized treatment questions, we’ve had great questions asked that benefit everyone.

The Q&A sessions are fun and even entertaining because sometimes the experts have differing approaches and opinions. It speaks to both the science and art of treating the complexities of multiple myeloma.

This show is a series of such a Q&A sessions from our roundtable meetings.

At our St. Louis meeting, we had the privilege of having Dr. Morie Gertz, Dr. Keith Stockerl-Goldstein, Dr. Ravi Vij and Dr. Guido Tricot in attendance. Due to possible sound issues we may have had for each attendee question, I will pose the question asked by the audience members and then we will hear the expert answers.

Q: How is risk assessed?

A: Dr. Keith Stockerl-Goldstein: Gene expression profiling, which is again a much newer test although not done routinely is done from that initial bone marrow specimen.

Q: And that’s at diagnosis and relapse but not while in remission?

A: Dr. Keith Stockerl-Goldstein: It’s not looked at typically in remission.

A: Dr. Guido Tricot: But if it’s not done and you still have myeloma cells in your bone marrow, and especially if you have more than 10% of your bone marrow cells being myeloma cells, you can still do this test.

Q: And it will show up how?

A. Dr. Guido Tricot: When you do the testing for the plasma cells they first select only the plasma cells and look at those and will see what the abnormalities are. They may be a little different from what you had in the beginning – because of the treatments, they may have changed a little bit and may have selected a different clone than you had in the beginning but you will still find extremely important information in that assay. But you have to have abnormal cells in the bone marrow. If you don’t have abnormal cells in the bone marrow, you cannot find the abnormalities.

A. Dr. Ravi Vij: But the significance of high risk myeloma is most at the time of initial treatment and initial diagnosis. At relapse, nearly all myeloma becomes high risk myeloma by definition, so the significance of some of these things that we’ve done may hold true for first relapse as well, but when you go beyond that, I think that again, the information we may have, we know that myeloma becomes cytogenetically high risk but the behavior of most of the myeloma at that time is more like high risk once you have second, third relapse. Do doing it repeatedly at fourth, fifth relapse at this time I don’t know how much information it provides.

A. Dr. Keith Stockerl-Goldstein: And also to clarify, we often do cytogenetic and FISH testing on every bone marrow specimen (at their facility). It’s not to look at changes in risk, but even when we’re looking after treatment, after transplant, to see if you are in remission if we know that your cells had a specific abnormality, we can search for it and get a higher level of understanding. Under the microscope we don’t see the cells but we can 2% of them by doing the FISH testing. It’s often done but as Dr. Vij mentioned, does it help us prognosticate all the time? No.

Q: Is the 11;14 translocation a high-risk feature? I understood that it was not.

A. Dr. Guido Tricot: The 11;14 translocation is a good prognostic indicator. But with time you can acquire additional abnormalities such as the deletion of 17p and then it becomes much more difficult to treat this disease. But in general it’s a good prognostic factor. The thing that you need to know about 11;14 is that it’s one of the most difficult to get stringent complete remission or MRD of all the diseases. And it’s not uncommon that still when people are in a complete remission that you can still find, if you have sensitive enough techniques, some form of disease with 11;14 – much more common than with most other translocations. But no, it’s still a good disease.

Q. If at diagnosis you had no chromosomal abnormality, later with repeated relapses, can that change or are other myeloma clones becoming more active?

A. Dr. Guido Tricot: I would say that the people who have no chromosomal abnormalities if you do specific enough tests with myeloma between 0-1% have abnormalities, it’s just how specific your test is and how sensitive your test is. If you do regular metaphase cytogenetics, you will find that 2/3 have no abnormalities, but that’s because you don’t look at the right cells. With FISH it’s 90% plus, with gene expression profiling it’s 99% plus. So people who have no abnormalities when they have active disease either you hit a spot where there was no disease at that time and you should try to find another bone marrow spot, but everybody has abnormalities. Myeloma is a very chaotic disease and lots of abnormalities.

Q. I notice so many of the drugs are combined with dex. What does it do and why isn’t there a replacement coming along for that stuff? What do we do as patients to suggestions for taking dex ?

A. Dr. Morie Gertz: Let’s go back to well before any of the effective chemotherapy drugs were developed and just say “What about dexamethasone all by itself to treat myeloma?” Fifty percent of patients who take dexamethasone alone as a single drug will get a 50% reduction in their myeloma protein. Dexamethasone is a solo agent – a highly effective treatment. It directly kills myeloma cells. Because the side effects of dexamethasone are different from the side effects of all the other drugs, it’s combined in almost every single regimen because it has a separate toxicity profile. Having said that, the insomnia, the mood swings, the withdrawal fatigue, the steroid rage, are all very realistic and experienced myeloma doctors recognize that all treatments are a balance of the bad side effects and the good side effects and it’s typical to make compromises over time so that the steroid dose is modified. In fact, just to have some perspective, if you go back 10 years – today you would take dexamethasone four days out of 28 days once a week. It used to be 12 days every 28 and the trials demonstrated although it was efficacious, there were so many bad vascular side effects that the 4 days turned out to be better. And of course I haven’t even talked about what it does to your blood sugar, what it does to the integrity of your bones and I’ve seen a couple of people develop bowel perforations as a result of dexamethasone. It’s bad for your immune system, cosmetically not so pleasing – the bruising on your arms are all real, issues, but again, everyone on the stage recognizes this over time and has developed the experience that not to adhere to necessarily what is written down as the dose, but to make adjustments appropriately over time.

Q: Is there any relationship between treatments and other diseases (secondary cancers)?

A: Dr. Keith Stockerl-Goldstein: I think what you are talking about are secondary cancers. Myeloma, if it comes back is myeloma but what can happen as a side effect of some of the treatments is that new cancers can develop – either cancers in the bone marrow like leukemias or lymphoma. Other tumors can be increased and we know that it seems to be associated with lenalidomide maintenance. But once it’s myeloma, it’s always myeloma.

Q: Is there anything in the research that shows how to predict secondary cancers?

A: Dr. Guido Tricot: There are risk factors. If you get radiation therapy, you increase your risk. If you get Revlimid, you increase your risk. With any type of therapy you have to remember that there is never a free lunch. Every therapy has side effects. But in general, what kills people is not the secondary leukemias or secondary cancers, it is the original cancer. And you need to make sure that you treat your original cancer well enough so that the chances of dying from that cancer is minimized.

Q: Is myeloma genetic?

A: Dr. Morie Gertz: So I think the question most people ask in the office is should I have my first degree family members screened and have their proteins checked periodically to see if they are going to get myeloma. The answer to that in our practice is no. And I think again it can be sometimes confusing when we talk about genes and genetics to separate that from heredity because the abnormal genes everyone is referring to and Dr. Tricot referred to in the first question – the genes are abnormal only in the plasma cells, only in the myeloma cells. The other cells of the body don’t show these gene abnormalities. And so you can have genetic changes in the myeloma cells that have important predictive value for risk but that has nothing do with whether your brother, your sister, your kids, your aunts and uncles will or won’t develop multiple myeloma.

A: Dr. Guido Tricot: And when you are in a complete remission, all those abnormalities are gone and so it is not in your normal cells.

Q: What can be done to not lose muscle mass with this disease?

A: Dr. Morie Gertz: That’s actually a really great question. It’s hard because particularly with dexamethasone can cause muscle weakness and I think going on chemotherapy or you’re hospitalized or stem cell transplant you get into this use it or lose it and so it goes about the diet – not a specific diet but it needs to be a healthful diet. Although I’m not sure I agree with Dr. Tricot about the alcohol I’m allowed to consume (wink). But the business about activity is really quite important. I mean a cancer diagnosis isn’t a free pass to stop being active and become sedentary. There’s no way I think to specify what is the correct activity but remaining active I think is an obligation every patient has to the best of their ability. Sometimes that’s hard if it’s hard to stand from a sitting position or if you can’t feel where your feet are – these are very real issues but I think we each have an obligation to maintain that activity level and I think that is not a trivial question at all.

A: Dr. Keith Stockerl-Goldstein: I think I should expand that activity is not just important for muscle strength but also for keeping the bones strong. We know that walking helps prevent bones from thinning and we already know there’s going to be a bone problem from the myeloma.

Q: If you don’t qualify for a clinical trial, or there isn’t one available, how does off-label drug use work?

A: Dr. Keith Stockerl-Goldstein: As physicians we can prescribe any medication we want if we feel that there is an indication but (you’re going to pay) that’s the issue is that the insurance company may not pay for off-label use and so these drugs as we mentioned are all very expensive.

Q: What is off-label (you mentioned earlier the drug venetoclax)?

A: Dr. Keith Stockerl-Goldstein: So a drug when it is approved the FDA gives it specific indications. A drug like bortezomib when it was first approved was approved just for recurrent myeloma. It’s now approved for mantle cell lymphoma but if you tried to use it for mantle cell lymphoma, again a different type of cancer, before it had that approval, you probably would not get reimbursed. Now there are some things that changed that a little bit Some drugs don’t have an FDA-specific indication for let’s say myeloma can be used for myeloma, and insurance companies may pay for it if it is in what Medicare has as a formula and things get into that formula based on a variety of things – the NCCN guidelines, which I mentioned (that list of agents). If a drug is in the NCCN guidelines at a certain level, then it will make it into what we call the compendium and typically the insurance companies will pay for it. The drug we were talking about is certainly not at that level.

Q: But if it’s good for the 11;14 translocation, it doesn’t translate for them?

A: Dr. Keith Stockerl-Goldstein: That’s very early in research. This drug and how effective it is, what it’s interaction with the 11;14 is. As a single agent only 15% of people responded to it and again it seemed to be just in the people with 11;14 but the majority of people with 11;14 still didn’t respond. Two or three or four drugs may be necessary but those combinations need to be tested. As Dr. Tricot said, more drugs come at a cost, so not all regimens give or have multiple drugs. Some drugs are used alone.

Q: Would you expect anybody who’s had a double transplants to relapse?

A: Dr. Guido Tricot: That’s a loaded question. The only thing I can tell you is that with the most intensive treatments where you give two autologous transplant back to back within three months and at least two years of maintenance therapy, that 50% of your patients are still without any sign of progression within 10 years. And nobody is going to convince me that if you can keep people in a complete remission for 10 years without any evidence of disease recurrence that this is not going to be a curable disease. That doesn’t mean that those 50% are going to be cured, but a fraction of those 50% are certainly going to be cured.

Q: Do you know what causes multiple myeloma?

A: Dr. Morie Gertz: Those type of epidemiological data are very difficult. I found in my practice that 100% of myeloma patients regularly think about sex. That’s something that we’ve identified as a risk factor (ha ha) but environmental, occupational, all of us here have seen bank presidents and politicians and and custodial engineers all develop myeloma and I don’t’ think there’s any common thread with regard to environmental exposures or occupational reasons that explain myeloma. It’s true that that if you’ve been exposed to extensive radiation, that is a risk factor in myeloma, but that history can only be found in 1% of myeloma patients. For the majority, we don’t know why they developed it.

A: Dr. Keith Stockerl-Goldstein: There does seem to be some association that goes along with that from the government with Agent Orange exposure. The importance of that is not that the disease acts differently or that it could be prevented, because Agent Orange shouldn’t be around anymore, but it is important for veterans who were in Vietnam and developed myeloma and other malignancies and there are benefits from the VA for that group of people.

Q: With the list you showed of drugs available in 2003 and now in 2016, will what is prescribed be determined by the genetic features or does doctor opinion and region come into play in what you are going to get prescribed?

A: Dr. Keith Stockerl-Goldstein: It’s a variety of things and that’s why we really need to individualize. Certainly the genetic signature is important but we also have to take into account other medical problems, someone whose got diabetes we have to be careful about dexamethasone for example how much we give. Someone who has peripheral neuropathy already from something like diabetes, we have to be careful if we are giving drugs that can cause that. There’s a variety of things that go into that. Overall, performance status or frailty is important. I think one of the reasons to see a myeloma specialist is to make sense of what’s the best option for you out of that very large list.

Q: You keep referring to 11;14. What does that mean for those of us who don’t understand science?

A: Dr. Guido Tricot: What it means is that part of chromosome 11 has gone onto part of chromosome 14 and part of chromosome 14 has now gone to chromosome 11. It’s a balanced translocation and the reason why that happens is that oncogene – the gene that makes the cancer cells grow – does much better if it is under the direction of the promoter 14 than on the promoter on chromosome 11. It tries to help itself by doing that.

Q: What is a plasmacytoma that grows outside of the bone marrow in myeloma? What is it? How should it be treated?

A: Dr. Keith Stockerl-Goldstein: These are all the same disease. It’s a malignant plasma cell. So a normal plasma cell – we all have them – they make antibodies to fight infection and a series of events happens and it becomes a cancer. That cancer can show up in a variety of ways. It can show up as multiple myeloma, but it can also form separate tumors. We call those plasmacytoma. There are some people who have a solitary plasmacytoma and have no evidence of disease in their bone marrow and that gets treated in a very specific way.

Q: I tried to get into a CAR T cell trial over the summer at another facility and I got no support whatsoever. I was on my own making phone calls calling my doctor’s office several times a week and hearing nothing back. It was the most frustrating thing imaginable.

A: Dr. Ravi Vij: So the thing is that we do have the CAR T cell trials right now for leukemia and lymphoma but we do not have them for myeloma. They are actually only available at select centers – UPENN and the NCI at the moment. Unfortunately we are not able to tell you if you are eligible for their trial. You have to be screened at their institutions and I can tell you I’m sure that they have long waiting lists because they are available at few centers and so much recognition of the technology now. But I think that again we ask advocacy groups to often help facilitate this kind of referral. In select cases if we know the investigator we can make a call but it’s not always clear who at the other end is the person to reach out to. Hopefully we can work with the patient advocacy groups to help find a CAR T cell trial.

Q: What’s our overall takeaway? What do we do today? What do we do tomorrow when we visit with our doctor?

A: Dr. Morie Gertz: I think it’s fair to have a discussion with your provider that even if things are going well right now what their thoughts are on “what would I do next?” And I think I share the cynicism that there is a reluctance to refer. I think all of us have seen patients who by the time they are referred there is very little for us to offer and we have doubts and wonder why we haven’t seen some patients 6 or 12 months earlier.

A common theme I think you’ve heard is try to advance the science. Enroll in a clinical trial. Asking about what will follow is #1. Secondly, whether there is an opportunity to get in on the ground floor, if you will, with regard to new therapies. I’ll tell you a personal story. My mother’s IgA MGUS turned into multiple myeloma. It seemed obvious to me that she should be enrolled in a clinical trial. And so we flew her up and I think she first got access to Revlimid in 2006 which is long before it was actually widely used. She went on a clinical trial with melphalan, prednisone, and lenalidomide because it seemed to me that 1) it would be a way she could access a drug early 2) get it for free and 3) advance the knowledge in multiple myeloma so that successive generations would benefit from the information.

A: Dr. Guido Tricot: In my opinion the most important thing is that the treatments are not unnecessarily given but directed by people who know this field in and out and that even if you are already on some kind of treatment that you should still try to ask for a second opinion to see if you are on the right track – if the treatment you are being given is right for you then go from there.

Thanks for listening to another episode of Myeloma Crowd Radio. Join us for future shows to learn more about the latest in myeloma research and what it means for you.

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About Author

Jenny A

Myeloma survivor, patient advocate, wife, mom of 6. Believer that patients can help accelerate a cure by weighing in and participating in clinical trials. Founder of Myeloma Crowd, Myeloma Crowd Radio and the CrowdCare Foundation.

5 Comments

  1. Annette Kenney on

    I would like information on MGUS in relation to multiple myeloma? I have MGUS and my mother died of multiple myeloma. Is there anything that can be done prior to full blown myeloma for the MGUS?

    • Jenny A

      Annette,
      I suggest you join the MGUS and smoldering myeloma observational study (called PCrowd) run by Dr. Irene Ghobrial at Dana Farber. Her goal is to identify who will and will not progress to myeloma and to prevent that progression. In this study, you simply send her blood or bone marrow samples (taken at your facility) and mail them to her. She is keeping a database of each patient to look for genetics, trends and other signals. I’m sorry to hear about your mom. Myeloma is not typically a familial disease. Here’s the link to more about the PCrowd study and she would love your samples!

  2. Myeloma is a heart breaker. With no pre screening for blood cancer, I shuttled my wife Annie from specialist to specialist for 18 months. It was agreed that she wasn’t well, but reluctant to send her to the cancer center. I’m May of 2008 she was finally sent to the cancer center. After the bone marrow biposy results came in, it was apparent from the look in the
    oncologist’s eyes, Annie was in trouble. She had stage 111 aggressive multiple myeloma. I was told privately she had 3 or 4 weeks to live depending on, if she could take therapy or not. She immediately failed Velcade, which he wanted to use with 25 mg of Revlimid if it was approved. It was approved, 21 days on, 7 off, for 4 months with 40mg Dex on day 1,8,15, & 22 of each cycle. Almost 4 months to the day of introducing Revlimid, Annie had a full remisson, or no signs of disease. Looking back, in the 3rd week post diagnosis she had 2 broken femurs, broken hip, and a collapsed spine Her bone marrow was 80% myeloma. My point: Her oncologist, the late Dr. Moore Sr., had 39 years expetience with blood cancer, and with the help of Revlimid and Dex, pulled off a miracle. Annie had a stem-cell transplant while in remission, but, after a traumatic and painful battle, we lost her at the 2 1/2 year point. From the time of diagnosis, Annie was always sick. What a tragedy. Thank you so much for all that you do to help others. This is an inhumane disease and no one should have to suffer as she did. Because of Annie

  3. My 42 year old special needs daughter was diagnosed with MM early December. She had gastric issues and hospitalized for 10 days in October 2016. Determined to have gallstones was prepped for glaabladder to be removed…..egd provoked her throwing up blood….biopsy done and I believe MM was suspected. though I was not told at the beginnings. After a multitude of tests and procedfures, this diagnosis came and she has the trasnslocated genes mentioned. As her mother, legal guardian, knmowing her and seeing her today, we will not do chemo. She has limited understanding of this illness that isn’t going away……I cannot put her through this ordeal when I know the disease iis advanced and aggressive. I pray they find answers for future generations. Once the foundation of this terrible disease is found to be genetic, death is imminent. I chose in home hospice so that however long she has, comfort is our goal.

    Grow in Grace

    • Jenny A

      Isabel, is your daughter being seen by a myeloma specialist? Having a high-risk feature is not a death sentence. There are other features that can off-set the high risk features. For example, if you have high risk features but also have trisomies, this is a good thing. Additionally, every myeloma case is incredibly different. There is no one-size-fits all kind of myeloma or treatment. I highly suggest that you have her seen by a myeloma specialist and not a local oncologist, They know this disease inside and out and can give you more ideas about how severe her situation is.

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