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Interview with Dr. Thomas Martin: New Treatments for Multiple Myeloma

Hear Dr. Thomas Martin, a blood disorders specialist at UCSF Medical Center, discuss the latest therapies for multiple myeloma, the second most common cancer of the blood and one that's very difficult to treat. Martin discusses stem cell transplants and new drug combinations that are giving him hope for a cure. He's joined by one of his patients Lisa Considine, 56, an associate vice president of fundraising at the City of Hope and a former UCSF employee.

Considine was diagnosed with multiple myeloma in 2007, after battling fatigue and several viruses that she couldn’t seem to shake. Her husband insisted she see a doctor. Tests showed she had kidney failure and was immediately admitted to the hospital. Blood work and a bone marrow biopsy confirmed she had multiple myeloma, an aggressive form that required immediate chemotherapy. After a week in the hospital, she began to prepare for a stem cell transplant. The transplant was performed in April 2008 and in August, a bone marrow biopsy showed a successful response. A few months later, she went on maintenance therapy of three medications — Velcade, Thalidomide and Dexamethasone (VTD).

Considine experienced severe neuropathy, or painful nerve damage, which is one of the side effects of treatment, and still sees an acupuncturist for relief. In November 2010, she started taking the drug Revlimid for maintenance therapy. She gets blood drawn every four weeks, takes Zometa for her bones and receives intravenous immunoglobulin as needed.

In Memoriam: "After a courageous six-year battle with myeloma, Lisa Considine died on Feb. 27, 2013. Her words of encouragement and positive spirit, however, should continue to offer hope to others. Our thoughts and prayers are with Lisa and her family."

— Dr. Thomas Martin

Photo by Tom Seawell

Interview Transcript

Andrew Schorr:

Myeloma, a cancer of the blood, can be difficult to cure. Fortunately, new treatments are helping patients live longer and live better. Coming up, Dr. Tom Martin, a blood disorders specialist at UCSF Medical Center, will discuss the latest treatments for myeloma. You'll also hear from his patient who is doing well. It's all next on Patient Power.

Hello and welcome to Patient Power sponsored by UCSF Medical Center. I'm Andrew Schorr. I am a leukemia survivor, a blood cancer. Another blood cancer is multiple myeloma. That's when the body produces too many plasma or myeloma cells. The cells produce antibodies that the body doesn't need and they can form tumors and cause other problems such as bone fractures and kidney failure. Over the years, myeloma has been thought to be a fatal condition, but there's been a lot of progress and we're going to hear about that.

Lisa's Story

Let's hear about this first through the eyes of someone who lives in the San Francisco Bay Area. That's Lisa Considine. She's 56 now, but back in 2007, she was diagnosed with myeloma. Lisa thought she had maybe a recurring bronchial infection. She also thought, maybe she cracked a rib helping her husband with an art project. But Lisa, when you finally had the blood test and other tests, it was a real shocker, wasn't it?

Lisa Considine:

Yes, it was like the house fell on me, basically. I was hospitalized the night of my bone marrow biopsy.

Andrew Schorr:

Did you know much about multiple myeloma then? I know you used to work at UCSF Medical Center, and so you knew a lot of the staff.

Lisa Considine:

Yes, I knew a lot of the staff. I knew a lot about many of the other cancers, but frankly, I didn't know that much about multiple myeloma. I had just learned more because I was staffing a physician at another medical center where I work, and he is the head of stem cell transplant so I had some familiarity with the disease.

Andrew Schorr:

Suddenly, all this was becoming very much in your lives. Now, I mentioned that there were newer therapies and the initial combination therapy to get you ready for a stem cell transplant was new stuff, right? How did it work in preparing you for the transplant?

Lisa Considine:

It was effective and it got me to the point where they could collect cells. I think I did it maybe a little faster than we thought and it all went smoother than we expected considering how aggressive the disease was when I was diagnosed.

Andrew Schorr:

But your whole focus at that time — work, family, of course, you have two daughters, a husband, you had a very busy job. You had to focus on fighting the cancer. So that led to a stem cell transplant, and we're going to talk about that in a minute.

First you knock back the disease. You harvest stem cells, your own cells. Your body is attacking the cancer, sort of cleaning it up as best it can, and then you get those cells back. That happened over many weeks. How did that go?

Lisa Considine:

Getting ready for it took a couple months, and then I was in the hospital for not quite three weeks . Then, I went home and pretty much stayed as much in isolation as I could just because of infection factors.

Andrew Schorr:

Ultimately you recovered from that. How long did that take to begin to get back feeling better?

Lisa Considine:

A couple months. After a couple months, I was feeling like I could take a two-mile walk, jump in the pool.

Andrew Schorr:

Now, this was 2008. The other part of treatment was to go on a maintenance therapy post transplant. And you had one combination therapy that you went on for a while to keep the cancer at bay, right?

Lisa Considine:

Yes, that was the Velcade-Thalidomide-Dex combo.

Andrew Schorr:

Right. We're going to talk about that. So you did that for I think nine months.

Lisa Considine:

Well, I did the three of them for nine months, and then I dropped the Thalomid and continued the other two. The Thalomid was a little too much for me.

Andrew Schorr:

Now, you're on yet another medicine, Revlimid, which is a pill you take. And you go in for check-ups how often?

Lisa Considine:

Every five weeks.

Andrew Schorr:

And you're doing well?

Lisa:

Yes.

Andrew Schorr:

And how do you feel about the future, having coming through this?

Lisa Considine:

Well, you never know with myeloma. You can't get too cocky, but I've got to say if anyone is to get it now, they're fortunate because if I had it 10 years ago, the outlook would be more dismal. Getting it at a time when drug development and personalized medicine are pretty much scientific priorities at all the major cancer centers, and especially UCSF, and with the genetic profiling, it's going to play a big part in customizing treatments, especially for people who have this chromosome 13 deletion that I have, which makes it even more difficult to treat. So targeting, targeting each person's actually disease, is going to really help everybody.

Andrew Schorr:

And you've benefitted, you've benefitted from the leading edge of medicine today.

Combination Therapies

Andrew Schorr:

Well, let's meet the doctor who has played a key role in that for you, and that's your doctor, Dr. Tom Martin, who is a blood disorder specialist. He's associate director of the Myeloma Translational Initiative at UCSF. Did I get it right, Dr. Martin?

Dr. Tom Martin:

You got it right. Perfect.

Andrew Schorr:

So first let's start with Lisa's case. She mentioned just a second ago that she has this chromosome 13 deletion and we're talking about personalized medicine. So it's not a one-size-fits-all. It's really to look at that individual patient, even genetically, and see what treatments line up with them, am I right?

Dr. Tom Martin:

That is correct. On her initial presentation, her kidneys were not working perfectly so we had to take the chromosome test results and the kidney abnormalities in consideration before starting her therapy.

Andrew Schorr:

So you take a look at that person, and then, as Lisa said, it seems there's a broader array of medicines today. Talk about that for a minute. How far we've come in the tools you have.

Dr. Tom Martin:

In the last 10 years, we've had fairly dramatic improvements in the treatment of multiple myeloma, mostly because of three medications, and those are thalidomide, lenalidomide or Revlimid, and bortezomib or Velcade. Those three drugs have been very potent in terms of their anti-myeloma effects. Those drugs, together with autologous transportation, we think have improved the average survival for patients from maybe three to four years to hopefully as high as six to 10 years.

Andrew Schorr:

Well, I know Lisa is listening. We hope that you'll come up with yet other things that can improve that. And we'll talk about research before we're done. But let's talk about these medicines. They fall in classes, don't they? I know one like bortezomib or Velcade, that's a proteasome inhibitor. Then you have these drugs that have the last part of their name is "imid," so that's a different class, and these work synergistically together, is that it?

Dr. Tom Martin:

That is correct. So the proteasome inhibitors cause changes in the dynamics of the cell and the way the cell grows and the way the cell is able to turn over proteins. We try to say that the cell gets so full of these junk proteins that the cell wants to commit suicide.

In addition, the IMiDs try to turn off the blood supply to these cells and to the cancer cells, so they're turning off the blood supply or the food supply for them. They also change the cytokines or the other proteins that are important for cell happiness and cell growth. So the two together work synergistically and are probably our most potent group of medicines together providing an anti-myeloma effect today.

Treatment Side Effects

Andrew Schorr:

Now, these are very powerful drugs, and all of us who take medicines wish there was a free lunch, if you will. You could take a powerful medicine, fight an aggressive disease and not have any side effects. But they do have side effects. Lisa, in your case ,what sort of side effects did you have?

Lisa Considine:

Well, I had pretty severe neuropathy for the first two years, and, you know, with Thalomid you have horrible muscle cramps and all sorts of other things going on besides the fatigue. So I was taking Neurontin, the maximum amount, and then I realized I really didn't want to be taking more pharmaceuticals so I started trying supplements and using common things — fish oil and alpha lipoic acid, things you can get over the counter.

Andrew Schorr:

And you do acupuncture, don't you?

Lisa Considine:

I do acupuncture every week. It helps immensely. When I don't do it, the neuropathy starts coming back.

Andrew Schorr:

Doctor, what are the common side effects of these drugs? People are surviving and the quality of life is so important, but what are the side effects and do we have medicines, as she alluded to, and other ways of helping people do better?

Dr. Tom Martin:

Absolutely. So Lisa did have some of the standard side effects that we see. From the IMiDs, the big side effects are fatigue, a propensity for forming blood clots and lowering of the blood counts. Those tend to be the most common. Some people can get rashes.

On the proteasome inhibitors, like bortezomib, neuropathy tends to be a more significant side effect. It also can cause some blood count abnormalities and sometimes some GI symptoms like some nausea or some diarrhea. Now, we do try to put everybody on a cocktail of supportive care medications to try to ameliorate some of these side effects, including anti-nausea medicines, anti-diarrheal medicines.

Like Lisa was alluding to, there is a cocktail of medicines to try to prevent neuropathy, and we use alpha lipoic acid, L-Carnitine, vitamin B6. Other things people have tried are the fish oils or the cocoa butter rubs to the feet and acupuncture, and I think all of those actually work quite well in individual cases.

Andrew Schorr:

You have drugs that deal with the bone complications of the disease as well.

Dr. Tom Martin:

Absolutely. So the most important thing with myeloma is to try to keep the skeleton as strong as possible, and the number one thing that does it is exercise. So for most of my patients, I tell them exercise is part of your regimen. It's part of your medication regimen. You have to do it to keep the bones strong.

We also recommend vitamin D for everybody because almost everybody is vitamin D deficient. A supply of vitamin D, calcium supplementation, and a type of drugs called biphosphonates, which are drugs that try to keep the bones strong. The key ones are Zometa or Aredia. Most people have had dosing on one of those two medicines.

Role of Transplants

Andrew Schorr:

Let's talk about transplant. We mentioned that Lisa had a stem cell transplant. There's often controversy about these transplants. Lisa had an autologous stem cell transplant. Her own cells were cleaned up and given back to her. Where are we now with that?

Dr. Tom Martin:

That's a really good question, and it is a hot topic for debate. I will say that in the next five to 10 years, we'll have more information to answer those questions.

There's a study in the United States, together with France, on patients getting up-front transplant versus waiting and doing transplant later, and that's a randomized study which we won't have data for five to 10 years.

A second study in the United States is randomizing patients to one transplant versus two transplants versus one transplant with some maintenance or consolidation type therapy. Those are the active issues in the U.S.

At the current time , I think if patients are less than age 65 or less than age 70 and are in good shape, those patients should really consider autologous transplant as part of their regimen. What we know from clinical trials to date is that it probably does increase the remission duration from anywhere between 12 and 18 months, so you get a longer remission duration when you do autologous transplant as part of your first line of therapy. You get some treatment, maybe lenalidomide, maybe bortezomib first, and then you get a transplant, and that hopefully will again improve your remission duration for over a year.

Andrew Schorr:

Related to the medicines that people go on for maintenance, that seems really important, doesn't it? And Lisa did that to keep the cancer at bay. Is that your view?

Dr. Tom Martin:

Absolutely. There are data from two randomized trials, one in France and one here in the U.S., that show that patients after an autologous transplant, if they went on Revlimid maintenance, their remission duration lasted about four years whereas if they didn't take maintenance or in fact took a placebo pill, their remission duration was on average about two years. So it almost doubles the length of their remission duration.

So I do think if you're going to undergo an autologous transplant, you want to get as long a benefit as possible, and going on a maintenance therapy afterwards — and maintenance is meant to be nontoxic — helps prolong that remission duration. I think it works really well, hand-in-hand.

Andrew Schorr:

Dr. Martin, what about the risk of a second cancer from any of these drugs you take as a maintenance. Maybe you toy with the immune system where some other cancer could develop.

Dr. Tom Martin:

It's a really hot topic and I just want to put it in perspective for patients. In the French trial of 300 patients who basically got an autologous transplant and then went on lenalidomide maintenance, 15 developed a secondary cancer down the road. Among the 300 patients who got the single transplant and then went on placebo, five patients got a secondary cancer.

It was different, but the absolute numbers are really not that high. Three years later, many more people relapse on the placebo group. More than 150 of those patients would have relapsed from their myeloma versus far fewer if they took lenalidomide. So right now, we're trying to assess who is at risk for these secondary cancers, how long a Revlimid therapy puts you at risk for secondary cancers so that we can adequately prescribe these medicines in maintenance fashion.

Ongoing Research and Treatments on the Horizon

Andrew Schorr:

Looking forward, you've seen tremendous change in this field. Lisa has benefitted from it. I hope she'll benefit more if there are new agents that are important for her. Where are we with other medicines that may be approved soon or look promising with FDA approval?

Dr. Tom Martin:

I think one of the take-home messages for everybody is this is a great era for treatment for myeloma. We have many new drugs that are in clinical trials.

If we went to clinicaltrials.gov right now, we could pull up almost 500 trials that are going on in the U.S. for patients with myeloma. It's really dramatic.

We have two blockbuster drugs that will soon be approved for use, I think ,within the next year. One, carlfizomib, which is a next generation proteasome inhibitor like bortezomib or Velcade, and that's coming from Onyx. And the second is pomalidomide. Pomalidomide is the next generation lenalidomide or Revlimid, and those two drugs will be the most powerful drugs, in my mind, that we have for myeloma. Within the next year, hopefully, they'll be out and available. Those drugs will be used as what I consider backbone drugs, in other words, part of almost everybody's regimen when they start therapy for myeloma.

Then, there are a number of drugs that are support drugs or secondary drugs that work in synergy, and those include proteins that inhibit Akt. They're called Akt inhibitors. One of them that's currently in phase III trial is perifosine. We have histone deacetylase inhibitors. There's one, vorinostat and another one LVH 584 from Novartis that are far along in the clinical trials, in phase III clinical trials. And we have some monoclonal antibodies, medications that potentially bind to the plasma cells or make the plasma cells stick out to the person's own immune system so their own immune system will help kill them. Those drugs are again synergy drugs that will be used together with IMiDs and proteasome inhibitors.

So currently, most people start off with what we call a doublet or a triplet for their initial therapy for myeloma, two or three drugs. But I think in the future, in the next five to 10 years, people will be starting off getting four or five drugs as their initial therapy for myeloma, and hopefully that provides us with a better anti-myeloma effect. Everybody hopes in the next 10 to 15 years, we'll be able to say that this regimen can cure a certain percentage of patients with myeloma.

Andrew Schorr:

Where we are now, though, we can't seem to cure it in most people, it sounds like people in many cases can go on with their lives and do well.

Dr. Tom Martin:

That's absolutely true. Most of the combinations that we can prescribe at the current time, short of bone marrow transplant, are outpatient regimens, and the regimens can be modified so patients can go on with day-to-day activities. Often people can work while they're getting some of these therapies, and often they feel good enough to do quality-of- life things. Now, there are some patients who have more severe side effects and can't continue their job, and they just need to work with their doctors individually on what are the best agents for them to be most productive.

Advice

Andrew Schorr:

Well, it comes down to personalized care. I want to give the last word to Lisa Considine.

Lisa, somebody is listening who is just diagnosed or a loved one has, and it's pretty scary, as it was for you. What would you say to them because you now are in that phase where you're working and you go to yoga class and you do your acupuncture and you are with your family? What would you say to them, knowing that everybody's situation is different?

Lisa Considine:

I think the most important thing is to take control of it as much as possible and be proactive. Don't just let it all happen to you. You put your energy into being a well person, and it's really hard because you feel pretty bad and you don't have a lot of energy, but you need to reach out and kind of gather the troops.

Have everybody support you, your family too, because basically when you're diagnosed, they're diagnosed too. They're going through the same thing. Even if you haven't been an inner person, meaning not focused on your inner life, it's time to start meditating. It's time to start doing things that maybe you've never done before, but you need to focus on yourself and be really positive. And do your research too.

Andrew Schorr:

All good advice. Lisa Considine, we want to wish you all the best.

Lisa Considine:

Thank you.

Andrew Schorr:

You have two daughters, one out of college, one getting out of college. I hope you have many, many years with them and if they're getting married you can dance at their weddings and have grandchildren and all that stuff. All the best to you. Thank you for being with us.

And Dr. Tom Martin, so devoted to Lisa and other folks with myeloma, all the best to you in your clinical work and your research. Hopefully, like you say, down the road we can say we can cure a lot of people. Thank you for being with us.

Dr. Tom Martin:

Absolutely.

Andrew Schorr:

This is what we do on Patient Power . . . connect you with leading experts like Dr. Tom Martin and really inspiring folks who are living with the condition like Lisa Considine. Thanks to UCSF for their ongoing sponsorship of Patient Power. And remember, knowledge can be the best medicine of all. I'm Andrew Schorr. Thanks for joining us.

Please remember the opinions expressed on Patient Power are not necessarily the views of UCSF Medical Center, its medical staff or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Recorded in April 2011

 

Reviewed by health care specialists at UCSF Medical Center.

This information is for educational purposes only and is not intended to replace the advice of your doctor or health care provider. We encourage you to discuss with your doctor any questions or concerns you may have.