Ask the Expert about the Latest Myeloma News

Andrew Schorr:

Okay. Now, I recognize that we have some people who are new to multiple myeloma who are listening, and so sometimes we’ll define these terms. There are a lot of acronyms in oncology and hematology. FISH testing, of course, is very sensitive testing to look at a patient’s individual situation, and you mentioned about genetic abnormalities, and here’s a question we got in from Paul, and he doesn’t say where he’s from, but here’s his story, and again, with these questions we’ll explore someone’s personal situation, but we’re going to globalize it as best we can.

Paul writes in, and he says, ‘I was diagnosed five years ago. I’ve been on just about all the treatments currently available. I’ve been on Revlimid for two months with pretty good results; however, my remissions have been short according to my multiple myeloma specialist physician due to the partial deletion of 13 and some other genetic irregularity. What novel treatment or clinical trials would you suggest as a possibility when Revlimid has run its course?’

Dr. Lonial:

Yes. Even something as what we thought was straightforward as deletion of chromosome 13 it turns out is actually a lot more complicated now as we get more and more data. So, I think that when you talk about deletion of chromosome 13 there are two different ways to get that result. The first way is using routine cytogenetics, which is a test that they do on the bone marrow where they actually look at the dividing cells and the chromosomes themselves and can identify that a part of chromosome 13 is missing.

The other way it can be identified is through FISH testing, which is as Andrew mentioned a much more sensitive test, but actually when you do FISH testing for deletion 13, 50% of myeloma patients have it. So, if you’re talking about a prognostic feature in which half the patients seem to have it, what real utility does it offer?

So what we’ve looked at now is looking at survival and duration of remission for patients with deletion 13 by routine cytogenetics as well as deletion of 13 by FISH, and it turns out that deletion of 13 by FISH really doesn’t have any prognostic implications anymore at all, so that the only deletion 13 that’s really potentially a negative adverse factor is when you see it by cytogenetics alone.

The second thing to say about deletion 13 is that all of the data that suggests that patients who have it by cytogenetics do poorly is data using convention, what I call “old fashioned” agents; steroids, chemotherapy, radiation. But there is data emerging now that says that new drugs like Velcade and like Revlimid deletion 13 doesn’t necessarily carry a negative prognostic feature.

So I think in many ways those prognostic factors that we look at may have to be redefined in an era where we use predominately novel agents or novel agents in combination with old drugs because the rules may have changed.

Andrew Schorr:

He also asked about so when Revlimid has run its course, so if you have a drug that may not be as effective, what do you switch to?

Dr. Lonial:

I think that, again, our approach has been often to use combinations. So, if you’re not getting what you want out of Revlimid, we will often add Velcade to it. I think that there are other trials now looking at Cytoxan plus Revlimid. I think that there are at my center alone two or three trials now combining new drugs that are not approved with Revlimid or new drugs that are not approved with Velcade, and I think that’s really the way to go. Once you’ve seen the commonly available agents, and even if you haven’t, I think a clinical trial is a good option, but this is a perfect setting in which you might benefit from either a combination of either Rev or Vel in the setting of a clinical trial agent.

Andrew Schorr:

Joan in Nashville is listening, and she just wrote in, ‘Please address relapsed myeloma choices. Is low-dose Revlimid as effective as high-dose Revlimid, and how does one determine what to take?’ Her key question I think for everyone is how does one determine when to stop one therapy and move to another?

Dr. Lonial:

So, the question about low-dose Revlimid versus high-dose Revlimid I think is, I’m not sure if that’s maybe being confused with the low-dose dex versus high-dose with dex with Revlimid. I mean, Revlimid I think for most of us when used with dexamethasone is started at 25 mg, and then the dose is reduced based on side effects or toxicity, but I’m not sure I would recommend the use of a lower-dose Revlimid with dexamethasone in the setting of relapsed myeloma except in the context of a trial or when you’re using it in combination with Velcade where we know 15 mg is the dose to start with for Revlimid and 1 mg/m2 of Velcade.

I think the other question about how do you know when to switch is also a good question. In our literature, we define progression as an increase of 25% from the lowest number of the M spike. So, for instance, if you M spike got down as low as 1, then when it went back up to 1.5 or 1.25 or 1.3, so we’re in that ballpark, that would be considered progression for most of the study. So when you look at that failure-free or progression-free survival, all those things, that would get you a tick mark on the survival curve, but practically speaking, just because a patient’s biochemical number goes from 1 to 1.5 it doesn’t mean that they necessarily need to be treated immediately, and what we will often do is follow them to get a sense for the tempo of the rise in that number.

I know that patients always like to say, “is there an absolute number at which you say I’m going to start you on therapy no matter what?” And the answer is no. There isn’t an absolute number because what we look for is some kind of a symptom that tells us that this level of protein is causing harm to the body or potential risk for the patient, and that can be simple things like increases in the creatinine that suggests the kidneys are now starting to get compromised; the development of a high blood calcium; progressive reduction in the hemoglobin or development of anemia; drop in the white count; drop in the platelet count; new bone lesions or bone fractures. Those are all things that I look for that say well, I can’t really watch this patient any more because the numbers are going up, but in addition to that they’re developing a lot more symptoms.

So, it’s really more of a judgment call as to when you start, and often I will tell my patients, you know you don’t have to start today, but your numbers are looking like it’s moving in the direction that we need to start doing something, so we can talk about doing it now. We can see again in a month where you are, but at some point in the near future we’re going to start you back on therapy.

Andrew Schorr:

Let’s talk for a minute about when someone is on therapy, when do they call the doctor or the nurse? Here’s a question we got in from Yvette in Denver, and she writes in, ‘My father-in-law was diagnosed with multiple myeloma four months ago. He’s losing a tremendous amount of weight and is receiving chemotherapy twice a month along with pills. The last few days he started getting blood in his stool. Should we be concerned or is this a side effect from chemo?’ And I would broaden this out, Dr. Lonial. So they’re worried about blood in his stool, and also other people have numbness and pain, so this whole dialogue about what’s a side effect, when should we be concerned, when should we call the clinic, or when should it result in a change in therapy?

Dr. Lonial:

Yes, I think blood in the stool is always something that you want to let your doctor know about, so that’s one of those relatively straightforward ones. It may not be a big issue or a major emergency, but it’s something that somebody ought to at least know about and potentially look into and determine whether or not they need additional workup, follow the hemoglobin, endoscopy or something along those lines, because often blood in the stool can be associated with a drop in the platelet count, and that certainly can be something that can be very serious and requires more aggressive therapy or modification of the dosing.

I think that the question about neuropathy is also another important one because we’ve found in the large, randomized, phase-III trials that we were able to minimize the incidence of grade 3 and grade 4 neuropathy, which is the worst of the neuropathy, simply by making appropriate dose modifications and dose reduction, and we find that that’s not always 100% translated into the community because for instance when somebody sees me, my whole team asks them every time they come in, tell me about your numbness. Is it worse? Is it better? How is it? So, we’re pretty sensitive to asking those kinds of questions, and unless you’re in an office that is used to doing that, especially with drugs like Velcade or thalidomide, you as a patient may not know to offer that information up, and so I think in that situation changes in numbness or tingling, the development of pain, those are all things that I think the oncologist needs to know about so that they can make appropriate dose modifications or hold the dose of therapy for a period of time to allow that to get better before resuming therapy.

Andrew Schorr:

Now, related to pain. How much is pain related to the therapy or just the effects of myeloma on the bone, and what do you do about that?

Dr. Lonial:

There are different kinds of pain. Obviously there’s bone pain, and that can be associated with the disease itself. There is pain that is associated with medicines like Aredia and Zometa. Sometimes we hear patients say that they got really bad bone pain a day or two after receiving that infusion, and then there’s pain associated with neuropathy.  So, obviously you have to tease them out.

I think it’s important that your doctor know before you start where you are and what’s causing the pain. A lot of bone pain may resolve with appropriate therapy, and we’ve seen that in a number of patients where they didn’t have a fracture, but they just had a lot of bone pain, and they had a lot of lytic disease by x-rays, and once they got through a cycle or two of therapy as their numbers got better and as their disease got better, the bone pain started to melt away, so I think it’s really an acute or an abrupt change in the kind of pain that you’re having or progressively getting worse pain over a period of time that that’s worth letting the doctor know about.

Andrew Schorr:

Regina writes in from Union Dale, Alabama, a question that I think anybody who’s diagnosed with cancer wonders. She says, ‘What can I do to help myself?’  So, you get asked that all the time. ‘Doctor, you’re going to do X or Y; what can I do?’

Dr. Lonial:

Yes. Well, there are probably several things, but I think that the most important thing that I tell patients is to try and stay as physically fit as they can because ultimately our ability to deliver therapy is limited by patients who cannot get around. They can’t care for themselves. They can’t get up and walk. If you’re physically not fit, that is going to change the doctor’s perception of what they’re going to use to treat you and how they’re going to treat you, so that’s incredibly important, doing your best to maintain muscle strength during periods where you are receiving steroids, and that is a real challenge because as you know steroids break down muscle mass. So, I think that that’s important.

I think a well-balanced diet is important. There are lots of things on websites all over the Internet that talk about use this supplement, use that supplement, don’t eat sugar, do eat sugar. I thing that there are a lot of myths, and there is very little hard scientific data about any of these processes, and so what I tell patients is eat a well-balanced diet, not too much of one thing or too much of another, and take a multivitamin a day, and that’s usually sufficient to guarantee that your body is getting what it needs and that you’re keeping yourself in a position to stay well for as long as possible.

Andrew Schorr:

I just want to make a personal comment. So when I was diagnosed with leukemia, and a kind of leukemia I’d never heard of, like maybe many of you had never heard of multiple myeloma, but chronic lymphocytic leukemia, so my wife saw somewhere on the internet, well don’t drink coffee and only drink carrot juice. So, she was making these carrot juice shakes, and remember I live in Seattle where Starbucks is headquartered, and we have one like every 10 feet, and I was a coffee drinker. So I went a year without drinking coffee.

Well, I have to tell you folks, now I’m happily, you know I’ve had a remission; I’m a 12-year survivor in a long remission, and I drink coffee a lot. I can’t tell any difference, so I’m just trying to enjoy life and stay healthy, but some of the things can just be crazy making, and then it’s so stressful to go through that. So, I certainly endorse what you said, doctor.

Okay, we have a question we received from Barbara. Barbara’s been a regular listener I guess to our series, and as I said, this is the eighth program in our myeloma series. She says, ‘One of the transcripts from a previous webcast mentioned getting Revlimid by intravenous infusion at the doctor’s office, and this made a huge difference in the cost of the medication to the patient versus pills. Has anyone gotten Revlimid by IV, and was there a cost difference?’

So, can it be administered by IV? What about this, doctor?

Dr. Lonial:

It actually can’t. It’s an oral agent. It’s not available by intravenous infusion. That’s not an option.

Andrew Schorr:

Okay, and then I want to mention for people, several people have written in, ‘Well, what are good sources for information?’ Well obviously our webcasts and the transcripts, and also the International Myeloma Foundation has a wonderful hotline, and I want to give that number: 1-800-452-CURE, and that works out to be 1-800-452-2873. They have folks there to help you gather information that’s valuable for you, and also they can also let you know where there are myeloma specialists.

Now, here’s kind of a complicated question we got in from Bill in Baltimore. Let’s weave our way through it. He says, ‘What do you recommend for relapsed patients who experience a high temperature, over 101 degrees, when they’re on Velcade/Revlimid, and blood cultures are negative and the fever is of unknown origin because it seems to be a sensitivity where taking Benadryl can reduce the sensitivity of the chemo.’

I’m not sure I follow all that, but he’s worried about the fever when, I guess, nothing shows up as an infection. So, does fever come in as a sensitivity to taking these medicines, and do you do anything about it?

Dr. Lonial:

Yes, I think we have a number of patients whose disease itself has fever associated with it. So, I think one of the questions is, is the therapy that you’re receiving really working? Because if it is, then that’s not something to worry about, but oftentimes we’ll see patients who have what we call “tumor fever” associated with their relapsed disease.

The second is that we’ve certainly seen it, and it’s been reported among patients receiving their first few doses of bortezomib or Velcade, that they will get a fever. Often it can be as high as 102 or 103, and it usually again for patients who respond it usually goes away, and that may be an associated release of growth factors associated with death of the plasma cells that’s causing that fever, but if it’s persisting for two and three cycles of therapy then that’s not likely the major issue.

I think that myeloma patients are so immunocompromised that a lot of times, if you look at just regular blood cultures or routine things, you won’t always find something, but you really have to look a little bit harder sometimes and do things like make sure that there aren’t fungal infections, and the most common obviously is yeast and other things like that and that there can be other types of infections, even aspergillus or mold infections that can be an issue in patients who have myeloma.

So I think it really, if it persists for longer than three or four weeks, then it probably does require in our hands here pretty extensive CAT scanning as well as a lot of different kinds of cultures to make sure you’re not missing some less common bugs or organisms.

Andrew Schorr:

Here’s just one question before we take a break, and then of course we invite a lot more. This is from Peter in Holmdel, New Jersey. He says, ‘When do you begin treating the patient who has relapsed after a bone marrow transplant? Do you treat when the M spike has reached a certain number, and if so, what would that be?’

Dr. Lonial:

Yes, I think that that’s often a challenging question, and we don’t have a specific number that we treat. We really look for symptoms more than anything else. Is the hemoglobin starting to drop? Are the blood counts starting to drop? Is the renal function starting to get worse? We look at the whole picture. Is the patient just not doing as well as they were three or four months ago, and that usually drives our decision to start on therapy, not necessarily an absolute number.

Andrew Schorr:

Okay, we’re going to take a quick break. We’re doing our eighth live webcast, a wonderful resource for you, and all the replays. So tell your doctor or tell other people you know, and today’s guest is a great one we’ve had before, Dr. Sagar Lonial, who is an associate professor at the Winship Cancer Institute of Emory University in Atlanta. We’ll be back in just a minute with more of your questions on Patient Power.

And here we are back very fast. Hopefully, myeloma, there can be bumps along the way, but it can be a long-term, chronic condition, and I am going to go down to spring training this week. For me, the Seattle Mariners play in the Cactus League in Arizona, so I’m going to go down with my son. We go, we’ve gone, this is like the fifth year in a row, I’m watching him grow, and we share our love of baseball, but the reason I’m mentioning this is the new pitching coach for the Seattle Mariners, many people remember him as just an outstanding New York Yankee and Yankee pitching coach, is Mel Stottlemyer, and many people have read the book that Mel wrote, but he’s living with multiple myeloma and has been for a number of years, so think about it. Here’s a guy; he’s in great shape, been an athlete all his life, has the diagnosis of multiple myeloma, and yet the Seattle Mariners, which hopefully can do well in the postseason, have really entrusted their pitchers to him, and I’d like to be able to think of myeloma that way.

What do you think, Dr. Lonial? When people come to you they’re terrified, they’re newly diagnosed or a family member is, and they say, ‘Well, what’s life going to be like after this diagnosis?’ It’s not for sure, and it’s individualized, but there are people like Mel Stottlemyer who just go on with their life and certainly are very productive.

Dr. Lonial:

Yes, and I think that that’s a big part of what we’re all striving to do as we talk about treating patients with myeloma is to get them back to their usual functional status. It’s not uncommon for me to see a patient at one-year post transplant, for instance, whose disease is under good control, and I ask them , so tell me what you’re doing in a day, and they say, ‘Well, I mess around the house a little bit,’ and I say, ‘Well, why aren’t you out doing more?’ And their answer is, ‘Well, I’m not just sure that I can do it, and I don’t know how long I’m going to feel this way.’ And I understand that concern, the anxiety about, you know, is this sort of a ticking time bomb kind of an issue, but I think that a main goal for all of us who treat myeloma is that we want patients to be back doing what they normally do and enjoying life and spending time with their family, and that may involve an aggressive treatment course for a short period of time, but at the end of the day if you’re not able to do those things, then all that effort and time we spent trying to make patients better is really for naught because they really should be out enjoying life and spending time with your family, so I think that’s a major goal for all of us.

Andrew Schorr:

Yes, I think that’s great advice, and I would urge people to do that, and I see that across all these serious illnesses. This weekend, again, I’m going to have a new friend on, Mary Sharkey, who is a six-and-a-half-year pancreatic cancer survivor, and there are not many, and she did have aggressive treatment, and it worked for her, and she’s going about her life. She has her checkups, but she’s going about her life, and that’s what that aggressive therapy was there for, for her.

Here’s kind of a complicated question, what I call a “grad school” question, from Scott in Buffalo, New York. So, our newbies just bear with us, but we’ll try to define things for you. He writes, ‘Recent findings have potentially linked the eventual relapse of multiple myeloma and some other cancers to the chemo-resistive properties of the cancer’s stem cell. Would you comment on any of the therapies in clinical or preclinical trials that you’re familiar with that have supposed cancer stem cell efficacy?’ And then he asks about a couple of drugs, which maybe you’ve heard of; GRN163L or another one cyclopamine, if I got that right?

Dr. Lonial:

Cyclopamine. Yes, I think that there is a lot, again, just as there is a lot of information and hype on the web about you should use this supplement or you should use this nutritional approach, there’s a lot of hype as well from the physician side and the basic scientist side about this so-called myeloma stem cell, and I think that intuitively it makes sense to me that there probably is a less mature cell that does not divide as much as the average myeloma cell does, although to be perfectly honest with you, a typical myeloma cell does not divide that often, so it’s not like a leukemia that divides much more rapidly. Myeloma cells tend to be a lot more indolent, at least in most subsets.

I think that there probably is some truth and validity to this so-called stem cell that may give rise to all the subsequent cells, and that might explain why we can eradicate large amounts of the disease, and yet patients are not truly cured because this cell is still alive, but I think it’s also important to realize that none of this has been proven in patients. There is no clinical data that suggests that any one agent or any one approach can hit the myeloma stem cell in a patient. There’s lots of animal data. There’s lots of mouse data. We know that we can cure mice of their myeloma, which I always laugh a little bit at because mice don’t get myeloma, so curing them of a disease that they don’t ever really get, what’s the real importance of that in my mind? But I think that it is helping us to ask important questions about the disease biology.

Right now I would say that there is no drug that’s tested or proven to have any efficacy against any kind of a “myeloma stem cell” and that I think if you want to take these agents, I think I would do it as a part of a clinical trial to really answer that question.

Andrew Schorr:

Okay. Now, Beth has called in from New Jersey. Beth, welcome to the program. Beth, I understand it’s your husband who has a diagnosis of multiple myeloma?

Caller:

That’s correct, yes.

Andrew Schorr:

When was he diagnosed?

Caller:

He was diagnosed in 2003 and underwent a stem cell transplant in 2004. My question is, it’s been recommended at this time that he begin Revlimid and dex because he seems to have come out of his remission, and he has some reservations about this combination, particularly the side effects of blood clots. Due to the nature of the disease, he experiences a lot of pain, in his legs in particular, and is concerned that he won’t be able to differentiate between the pain of a blood clot versus the pain that he already experiences, and therefore he’s a little reluctant to begin the drug. Is there any way that you can make him feel a little bit more at ease or explain to him how this is going to go?

Dr. Lonial:

Sure, sure.

Andrew Schorr:

Sure, and Beth, what’s your husband’s name by the way?

Caller:

Peter.

Andrew Schorr:

Okay, well let’s give some guidance to Peter. Thank you for calling, Beth.

Dr. Lonial:

I think that there are, first of all, there is no absolute right answer for what to do in the setting of first-relapsed myeloma. So I think if at the end of the day or whatever I say or whatever else, if you and your husband are not comfortable receiving Revlimid-based therapy, there are other options. Velcade/Doxil is an option. Velcade is an option. There are a number of other clinical trial options that are available as well. So, there isn’t just one option.

Now, I think that Revlimid/dex is certainly a reasonable choice to make in this clinical situation, and the risks of clotting and thrombosis is an issue, but I think with appropriate prophylaxis and with appropriate observation, it can be minimized to probably an area of about five to seven percent, somewhere in that range there. If you look at the incidence of thrombosis in myeloma patients across the board, it probably is somewhere around five to seven percent anyway in the relapsed-myeloma setting.

I think that the symptoms of thrombosis are not really usually pain. It tends to be more asymmetrical swelling. So, if you get a clot, you may get swelling on the right leg or the left leg out of proportion to swelling on the other side. So, the main symptoms are usually not pain per se as much as they are the swelling associated with one side or the other, so I think that if pain is an issue and you’re worried about confounding pain, that really should not be a major issue, but I think it’s important that anybody who receives Revlimid-based therapy be on some kind of prophylaxis to minimize or prevent the risk of clotting, and there are a number of ways to think about what to use for prophylaxis.

There is a paper that just came out in the journal “Leukemia” which is a consensus statement for many of us who wrestle with this problem on a daily basis, suggesting a couple of strategies for prophylaxis when you use Revlimid-based therapy, and again there’s no one accepted opinion, so I’m not going to tell you exactly what I would do in this situation, but there are options to reduce the risk of clotting significantly.

Andrew Schorr:

Okay and I think this underscores for Beth and Peter and others is for many myeloma patients your clinical situation is kind of a moving target and the knowledge about both the treatment of the disease and managing of side effects or potential complications, that’s moving too. So, I think you not only want to stay up to day yourself as best you can, but have a consultation and have a relationship with a myeloma specialist so as you heard Dr. Lonial allude to, he is reading that journal article that just came out in “Leukemia” and focusing on it because he’s been dealing with these issues all the time, so obviously he’ll be discussing that with his patients. Whether you’re one of his patients or consult with him or another myeloma specialist, I think it’s good to have that relationship.

Here’s a question we got in from Robert in Arlington, probably Arlington, Virginia, and I’ll read through this one. “For smoldering myeloma, stage I, asymptomatic, newly diagnosed, are bisphosphonates such as Aredia not appropriate to start as adjunctive preventive therapy to strengthen the bones in advance of myeloma’s destructive work, or are bisphosphonates only appropriate to repair ongoing, already damage bones?’ And he was referring to Mayo Clinic’s consensus statement. So the idea is, what preventive strengthening do you use for the bones or not, doctor?

Dr. Lonial:

Right, right, and again, I think you highlight a very important couple of pieces of information there. The first is the Mayo Clinic consensus statement, and I think having been one of the reviewers of that consensus statement, I can tell you that it was a consensus among Mayo physicians. It was not a national consensus statement. So many of us do not actually agree with their guidelines for use or not use of bisphosphonates.

I think the second piece of information I would offer is that for patients who truly have asymptomatic myeloma, part of that definition means that you don’t have bone disease, and so if you don’t have bone disease to date there have not been any demonstration that the use of bisphosphonates in that setting offers any significant benefit, and if you do have bone lesions, many would argue that you’re not asymptomatic myeloma, that you actually are symptomatic mye

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