A new study says immune therapies  can be more effective in treating certain kinds of cancers, like Melanoma cells, seen here.

A new study says immune therapies can be more effective in treating certain kinds of cancers, like Melanoma cells, seen here.

The battle against cancer includes familiar tools such as surgery, radiation and chemotherapy. But for some, a new treatment may be worth considering: Immunotherapy. It’s a strategy that involves activating a patient’s own immune system to beat back and even eliminate the cancer. Recent research demonstrates positive results with several kinds of cancers such as brain, bladder and skin. The treatment has proven effective in some cases when no other therapy has worked, but much more research is needed to determine in advance which patients are most likely to see results. A look at new research on using our own immune systems to treat cancer.

Guests

  • Dr Steven Rosenberg chief of surgery, National Cancer Institute, National Institutes of Health
  • Dr. John Sampson chief of neurosurgery, Duke University Medical Center
  • Dr. Suzanne Topalian professor of surgery and oncology and director, Johns Hopkins Melanoma Program at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Transcript

  • 10:06:53

    MS. DIANE REHMThanks for joining us. I'm Diane Rehm. There's a new class of medicines that tap into the body's own immune system to fight cancer. Research suggests that for some patients, these drugs prolong life and could possibly lead to a cure. Joining me to talk about immunotherapy cancer treatments, Dr. Steven Rosenberg of the National Cancer Institute at the National Institutes of Health.

  • 10:07:23

    MS. DIANE REHMFrom a studio at Duke University, Dr. John Sampson of the Duke University Medical Center and by phone from Chicago, Dr. Suzanne Topalian of Johns Hopkins University. And we'll be taking your calls throughout the hour. Join us by phone at 800-433-8850. Send an email to drshow@wamu.org. Follow us on Facebook or Twitter. And thanks to all of you for joining us.

  • 10:08:00

    DR. STEVEN ROSENBERGGood morning.

  • 10:08:01

    DR. SUZANNE TOPALIANThank you.

  • 10:08:02

    DR. JOHN SAMPSONGood morning. Thank you so much for having me.

  • 10:08:03

    REHMGood to see you all. Dr. Rosenberg, we've been hearing lots about immunotherapy in the past few days. Explain to us what's involved here.

  • 10:08:15

    ROSENBERGWell, let's put immunotherapy in the context of all cancer treatment. We have, up until very recently, had three main methods for treating cancer. We've had surgery, radiation therapy and chemotherapy. And those three treatments can, properly applied, cure a little bit over half of all people who develop cancer. So in many ways, cancer is a very treatable disease. The problem is the half that can't be cured by those three modalities resulted in almost 600,000 deaths in America alone.

  • 10:08:47

    ROSENBERGAnd so we've now seen in the last two decades the birth of a fourth method for treating cancer and that is immunotherapy. It doesn't use a scalpel, a radiation beam or a drug to treat cancer. What it does is it stimulates the body's own natural defenses, the body's own natural immune system that can recognize the cancer as foreign and attempt to destroy it. And immunotherapy is a treatment modality that stimulates the body's own natural defenses, its natural immune system.

  • 10:09:23

    REHMDr. Topalian, talk about the kinds of drugs that are being used to, you know, sort of take the brakes off a person's own immune response.

  • 10:09:41

    TOPALIANYeah. So the drugs that are described as taking the brakes off are called immune checkpoint inhibitors. The immune system has natural brakes that are meant to terminate immune responses at the right time, but unfortunately cancer cells can coop these mechanisms and they then become invisible to the immune system. So the idea behind these new therapies is to fight that shield that the cancer cells put up and to unleash the brakes on the immune system so that it can do its job in eliminating cancer.

  • 10:10:17

    TOPALIANThere are several different drugs in this class. You know, here at the annual ASCO meeting in Chicago attended by over 35,000 oncologists, there was a lot of news about one approach, which is called the anti-PD1.

  • 10:10:36

    REHMAnti-PD1. And tell me what kinds of cancers, for example, anti-PD1 might be able to address.

  • 10:10:49

    TOPALIANUm-hum. Well, the thing about anti-PD1 is that it provides what appears to be a common denominator for cancer therapies so it's effective in multiple different kinds of cancers. Different versions of anti-PD1 drugs that are produced by different pharmaceutical companies have been approved just within the past several months for patients with advanced melanoma, a deadly form of skin cancer, and also patients with an advanced type of lung cancer.

  • 10:11:22

    TOPALIANBut we heard a lot of new information at the meeting here in the past few days showing that these drugs have an impact on several other kinds of cancers, including head and neck, bladder, Hodgkin lymphoma. It's becoming a rather long list now and so there's a lot of activity in this space to perform the clinical trials that will determine if these drugs provide a benefit in terms of long term survival for the patients who are receiving them.

  • 10:11:57

    REHMAnd certainly giving lots of hope and optimism, I'm sure. Turning to you, Dr. Sampson, how do you determine -- well, let me start with this. To what extent have you, in your own neuro-surgery efforts, been able to employ immunotherapy?

  • 10:12:22

    SAMPSONSo I think immunotherapy is also very promising for brain tumors. And we've looked at a number of approaches. We've certainly started to work with the checkpoint inhibitors and have seen some very early promising results. But in addition to that, we've developed some vaccines that also seem to be promising in this field as well.

  • 10:12:40

    REHMWhat kinds of vaccines?

  • 10:12:43

    SAMPSONSo the vaccines that we've developed really stem from work that was done years and years go by Dr. Rosenberg where we look at some of the mutations that occur in these tumors and we found a number of mutations that were described by luminaries in the field like Bert Vogelstein and Darell Bigner. And some of these mutations actually are very specific to the tumor and so we're able to develop peptides that we can give to patients, sometimes in combination with some specific adjuvants, that train the immune systems to find those proteins throughout the body, even when they're hidden in the crevasses of the brain, and eliminate the cancer cells very specifically.

  • 10:13:20

    REHMDo I understand correctly that you've been using tetanus vaccines or tetanus medications to address some of these tumors?

  • 10:13:35

    SAMPSONYou're right. We have. It was a bit of a shot in the dark, no pun intended, but we thought if we could combine a tetanus vaccine with our cancer vaccines, we may stimulate or trick the immune system into recognizing the cancer. And as Suzanne pointed out, sometimes what happens with the immune system in cancer is it sort of shuts it down in various different ways and so the use of tetanus was really an attempt to trick the immune system to responding to the cancer vaccines because in general, we've had a hard time stimulating immune responses to vaccines in cancer.

  • 10:14:07

    REHMSo how did that work?

  • 10:14:10

    SAMPSONWell, it seems to work extremely well. In a small but randomized blinded trial, we were able to show that by giving the tetanus in combination with a vaccine that actually attacks a virus in these tumors, a common virus that hides out in these tumors, if you will, that we were able to generate a response in half of the patients where instead of living about a year, half these patients lived almost five years in this study, just by adding the tetanus to the vaccine.

  • 10:14:36

    REHMDr. John Sampson, he's chief of neurosurgery at Duke University Medical Center. Dr. Suzanne Topalian, professor of surgery and oncology at the Johns Hopkins Melanoma Program at Johns Hopkins University and Dr. Steven Rosenberg. He's chief of surgery at the National Cancer Institute. And of course, that is part of the National Institutes of Health. Do join us. Call us on 800-433-8850.

  • 10:15:20

    REHMDr. Rosenberg, you said at the outset that about half of the cancer patients are now being treated with one of these three traditional, if you will, treatments, chemotherapy, radiation or surgery. Now, what portion would you see being addressed, treated by immunotherapy?

  • 10:15:53

    ROSENBERGSo standard treatments that can be curative, largely surgery for most solid cancer, is certainly the major modality we have for treating solid tumors. Now, it's the solid cancers as opposed to cancers in the blood that comprise about 90 percent of all cancers and account for almost 90 percent of all deaths from cancer. So for those half of patients that we do not have effective treatments for, that have solid tumors, they have tumors that have spread throughout the body and that's where new treatments, innovative approaches come to bear.

  • 10:16:28

    ROSENBERGNow, there are three major forms of immunotherapy that can be used. There's a non-specific form that just stimulates the body's immune system or can take the brakes off the immune system as we've just heard from Dr. Topalian. Now, the first effective immunotherapy for cancer was described back in 1985, interleukin 2. It's a way to stimulate the body's immune system directly, as opposed to the newer checkpoint modulators which get rid of the inhibitors.

  • 10:16:57

    ROSENBERGSo there are two ways to effect a reaction. One, directly stimulate it, the other is to take off the brakes.

  • 10:17:04

    REHMAnd the question would be, how many of that half of cancer patients might be able to be treated in one of those ways.

  • 10:17:16

    ROSENBERGWell, unfortunately, right now, quite few. Dr. Topalian mentioned melanoma and that's been a poster child for immunotherapy because it contains a large number of mutations, more mutations than virtually any other cancer and that's what the immune system is attacking. Now, smoking-induced lung cancer also has a very large number of mutations because of all the carcinogens in cigarette smoke. But there are also responses in a select group of patients with kidney cancer and a small group of patients with colon or rectal cancer that happen to have large numbers of mutations.

  • 10:17:49

    REHMDr. Steven Rosenberg of the National Institutes of Health. We're going to take your calls, comments shortly. Stay with us.

  • 10:20:01

    REHMAnd welcome back. We're talking about a new class of medicines that tap into the body's own immune system to fight cancer. We have three guests with us today: Dr. John Sampson is chief of neurosurgery of Duke University Medical Center. Dr. Suzanne Topalian, professor of surgery and oncology at the Johns Hopkins University Medical Center. And Dr. Steven Rosenberg of the National Institutes of Health. Dr. Topalian, could you talk for a moment about how you determine which patients could be helped by this kind of immunotherapy we've been talking about?

  • 10:21:00

    TOPALIANWell, this is a huge area of research now is to try to develop markers that can help us identify which patients are most likely to respond to these treatments, so that we can spare the other patients having to be exposed to these treatments and spend time on something that's not really likely to help them. So in the laboratory, we focus on pretreatment and post-treatment tumor biopsies to provide clues for markers that might be associated with response to therapy. Some of these markers are proteins that are displayed on the surface of tumor cells.

  • 10:21:47

    TOPALIANOther markers that have been talked about just within the past couple of days at the ASCO Conference are genetic markers for patients with colon cancer, identifying a small subset but a subset that is very likely to respond to the Anti-PD-1 drugs. This is very much a work in evolution.

  • 10:22:11

    REHMInteresting. And Dr. Sampson, you mentioned using vaccines against existing tumors. What kinds of results have you seen?

  • 10:22:26

    SAMPSONSo we've really explored two areas. One is against a mutation that was discovered years ago on this -- on a surface receptor. There's receptors on all cells that allow signals to go from the outside to the cell to the inside of the cell. And sometimes when a cancer mutates, these receptors are changed in a way that has them on all the time. So the gas is always on these cells and they divide uncontrollably. Sometimes those receptors that have mutations, we can develop vaccines against those mutations. And there's a very common receptor that's upregulated in cancer called the epidermal growth factor receptor. And there's a specific mutation in that, that we have developed an immune response to.

  • 10:23:04

    SAMPSONAnd what we've been able to show is that if we can generate antibodies to that receptor, that those antibodies can actually kill those tumor cells directly.

  • 10:23:11

    REHMHmm. And I would think that the sooner you address that, the better. So therefore you've got to be able to identify those tumors which could be addressed very quickly.

  • 10:23:29

    SAMPSONAnd it's fairly easy to do that. We can even do that just from the blood of a patient, because tumor cells or DNA from the tumor cells actually leaks into the blood or into the spinal fluid of some of these patients. And we can use that to identify which patients may benefit. And then really early on in the vaccine regimen, we can show that patients that develop a robust immune response and a very high antibody response actually can be predicted to do very well with the vaccine and live much longer than those that don't develop the immune response.

  • 10:23:56

    REHMAnd Dr. Rosenberg, I know you wanted to comment on the use of vaccines as part of this larger immunotherapy system.

  • 10:24:09

    ROSENBERGThe search for vaccines against cancer has been going on for many, many decades. There are probably a thousand clinical trials that have been reported of cancer vaccines, including tens of thousands of patients. Thus far, there's only one vaccine that's been approved by the Food and Drug Administration, one for prostate cancer that can prolong survival by about three to four months. But there are very few responses. And all patients that receive it go on to progress and die of the disease. Now the vaccine that Dr. Sampson is working on is a very interesting one but obviously very early in its development.

  • 10:24:45

    ROSENBERGVaccines are simple to apply and therefore people are very anxious to find effective vaccines. They have very little in the way of side effects but, thus far, with very few exceptions like the one I mentioned. Dr. Sampson has some interesting results in an early trial in patients with glioblastoma. So hopefully this is an area that's going to continue to develop.

  • 10:25:08

    REHMDr. Topalian, let me come back to you on how patients react to some of these immunotherapy drugs that you have seen. What have been the side effects, if any?

  • 10:25:26

    TOPALIANWell, as we mentioned earlier, the Anti-PD-1 drugs are part of a class drugs that we call checkpoint inhibitors. So we're releasing the brakes on immunity and would like to be directed against cancer. Sometimes there are spillover effects in normal tissue. So this was to be expected. It happens in a minority of patients. In most cases, these side effects are mild. But in some cases, they can be severe. This is a new class of drugs. Physicians need to become more familiar with these types of side effects, how to recognize them early and how to treat them aggressively. And I think we're well on the way now for people to become familiar and to feel comfortable with administering these drugs.

  • 10:26:21

    REHMAll right. And now turning to the question of genetic engineering, Dr. Rosenberg, describe what you're doing in that field.

  • 10:26:34

    ROSENBERGOne of the very exciting areas of current immunotherapy utilizes the immune cells, the immune warriors of the body called lymphocytes, that are the immune cells that attack any organism or tissue that the body senses as not being part of self. And what we've been doing over the last several years is using these lymphocytes as a drug -- that is, taking the immune cells out of a patient, identifying those cells that can react against the cancer, and then returning them in large numbers to the patient. And that can be very effective in patients with melanoma. One can also take those lymphocytes and genetically engineer them -- that is, put in molecules that will enable a normal lymphocyte to actually recognize a cancer.

  • 10:27:21

    REHMAll right. So you're talking about manipulation at the cell level. But now, give me an example of how that may help a particular person with a particular type of cancer.

  • 10:27:40

    ROSENBERGSo, for example, the first patient ever successfully treated with this kind of genetic engineering was a patient that had a very refractory lymphoma that had spread throughout their body, had received multiple chemotherapy and other experimental regimens and it hadn't worked. We were able to remove their normal lymphocytes from their circulation, genetically engineer them with a retrovirus to insert into those lymphocytes, a molecule that would recognize the cancer, a kind of cell that didn't exist before in that patient. We then grew them to large numbers, returned them to the patient.

  • 10:28:14

    REHMHmm. Hmm.

  • 10:28:15

    ROSENBERGAnd that very first patient is now five years later and completely progression free of their lymphoma. And this has been now repeated not only at our institution but many others around the world.

  • 10:28:25

    REHMThat's fascinating. Dr. Sampson, have you seen any examples of your approach really having a dramatic impact on an individual?

  • 10:28:42

    SAMPSONWell, in fact, we have, Diane. I remember back in 2002, a young -- a patient coming into my office and she had, in fact, just won a beauty pageant, had just been married, and then had a seizure and had an MRI scan. And it showed a tumor and unfortunately quite a bad one. And she was the first patient to enroll on our vaccine trials. And I remember sitting in the clinic and talking with her and her telling me that she wanted to have children. And this type of disease is not the type of disease that people normally think about that. But I guess she just didn't know any better. This is the type of cancer that unfortunately takes patients' lives within a year, typically.

  • 10:29:21

    SAMPSONAnd so she was brave enough to enroll on our first vaccine trial. And now, more than 10 years later, almost 15 years later, she actually has several children of her own, still happily married and is having a -- from all we can tell -- a completely normal life. What residual tumor she had after surgery has disappeared and she's completely normal in every way now.

  • 10:29:42

    REHMSo in fact you used both surgery and a vaccine.

  • 10:29:49

    SAMPSONWell, unfortunately, for malignant brain tumors, we really have to pull out all the stops. And I agree with Dr. Rosenberg's comments completely. We have a number of things in our armamentarium. And immunotherapy is sort of the fourth arm of that group of treatments. And we really try to apply additional therapies to anyone with a malignant brain tumor, because the standard of care for us really just doesn't provide much survival. So she had surgery, radiation and chemotherapy. But then her tumor recurred. And at that point, she got the immunotherapy.

  • 10:30:21

    REHMI see. And that proved to be successful.

  • 10:30:26

    SAMPSONIt has been for over a decade and she's doing extremely well.

  • 10:30:29

    REHMI'm very happy to hear that. Genetically, Dr. Rosenberg, how different are different kinds of cancers? Or is there one central issue or tissue that makes something cancerous?

  • 10:30:53

    ROSENBERGAll of the characteristics of the human body are encoded in our DNA. And there are very long stretches of DNA that have no known function. But some stretches actually code for proteins that make us what we are. And there are about 23,000 of those instructions. We know that when a cancer starts, it's the result of mutational changes that occur in our normal DNA. Some of those normal proteins and -- have individual amino acid changes that change their function. And it's the sequential accumulation of those mutations that leads to a cancer. And unfortunately for finding good therapies, the sequence of those mutations and their identification can be quite different from cancer to cancer.

  • 10:31:41

    ROSENBERGWe know a few genes that are -- can be common. But most we do not understand and it's a conglomeration of genes all interacting together that are mutated that can result in the cancer phenotype and the cancer process.

  • 10:31:54

    REHMDr. Topalian, there you are in Chicago at a conference and I'm sure immunotherapy is being discussed at great length. The question becomes, how many physicians are aware of and may be in the process of using these approaches? Or is it new enough that many are not even educated sufficiently?

  • 10:32:28

    TOPALIANThe number of physicians who are now familiar with these drugs, that number is growing. And this conference, I think, is highlighting the fact that immunotherapy, as a general area, has now been accepted by the broader oncology community as a very important treatment modality, in addition to the more traditional modalities that Dr. Rosenberg mentioned. It's obvious that more education is going to be needed before physicians feel totally comfortable administering these drugs to patients. That's why people come to conferences, is to learn more about how to use these drugs. When is it appropriate? What markers are being developed that might hopefully help us to select patients for these therapies? And how does this fit in with the more traditional therapies?

  • 10:33:31

    REHMIndeed.

  • 10:33:32

    TOPALIANI would say that, you know, immunotherapy is not a standalone. And there are many areas of intersection with the more traditional therapies and even with other experimental therapies such as you're hearing about today: cancer vaccines, genetically engineered t-cells. So all of these can potentially be given in combination treatment regimens.

  • 10:33:54

    REHMAnd you're listening to "The Diane Rehm Show." We have a -- an email related to that question. "How available is immune therapy for cancer? Is it available at most major medical centers? Or is it just available experimentally?" Dr. Rosenberg.

  • 10:34:20

    ROSENBERGWell, as of now, there are several drugs approved by the Food and Drug Administration that oncologists can prescribe. There is Interleukin-2 for melanoma. There's an Anti-PD-1, the kind of braking the blockade that Dr. Topalian has talked about, and Ipilimumab. Those are two approved drugs. And so we're talking just about a handful of drugs, perhaps four or five, that have been approved by the FDA for very limited indications: melanoma, lung -- smoking-induced lung cancer. But those should be widely available to any oncologist now.

  • 10:34:53

    REHMAll right. Let's open the phones. First, to Leesburg, Va. Ashley, you're on the air.

  • 10:35:03

    ASHLEYHi, Diane. Thank you for taking my call.

  • 10:35:05

    REHMSurely.

  • 10:35:06

    ASHLEYWith the traditional forms of therapy, like radiology and chemotherapy, the quality of life is -- it really suffers. So I was wondering if there has been an improvement in quality of life with immunotherapy. And is it coupled -- I know that you had mentioned that it's coupled with other forms of those therapies that I just mentioned. But, you know, is it coupled with a change of lifestyle -- better eating, exercise, et cetera.

  • 10:35:34

    REHMDr. Sampson.

  • 10:35:36

    SAMPSONI think that that's one of the really important aspects of immunotherapy. And even though some of the early trials with immunotherapy can have some toxicities, in general, we are quickly able to figure out how we can use immunotherapies very effectively with minimal side effects. In our vaccine trial, for instance, patients will get a little bit of swelling at the site of the vaccine. But other than that, they tolerate the drugs extremely well and really don't have any major side effects. So I think that's one of the other things that is a really outstanding benefit of immunotherapy is that it's very, very specific and eliminates the tumor cells very specifically.

  • 10:36:13

    REHMDr. Topalian, have you seen side effects?

  • 10:36:19

    TOPALIANYes, we have seen side effects. Actually all of the forms of immunotherapy that we are talking about today have been associated with some side effects. When we think about side effects, we have to think about the benefit-to-risk ratio. And for the Anti-PD-1 drugs, we think that the potential benefit outweighs the potential risks.

  • 10:36:43

    REHMBut what kinds of side effects are you talking about?

  • 10:36:48

    TOPALIANMm-hmm. So with this class of drugs, the Anti-PD-1 drugs, we often observe immune-related side effects -- the consequence of releasing the brakes on the immune system with some spillover into normal tissues. And so we can see rashes. We can see inflammation in organs like the lung, the colon. We can see endocrine gland abnormalities, liver abnormalities. In general, these are mild and they can be reversed simply by stopping the drug.

  • 10:37:26

    REHMAll right. Dr. Suzanne Topalian of Johns Hopkins. Short break. More of your calls when we come back. Stay with us.

  • 10:20:00

    REHMAnd welcome back. We're talking about using the body's own ability to fight off cancers with the release of certain chemicals in the body, taking the brakes off certain forms of what we have inside of us to fight cancer. A very important tweet from Andy, while the research sounds promising, how does the new treatment compare in cost? Dr. Rosenberg?

  • 10:40:47

    ROSENBERGWell, any of the new treatments that have been developed have been the result of many years, often a decade of research that's finally left the pre-clinical arena and animal experiments, into human trials, and those are very, very expensive. Unfortunately, many of these new immunotherapies can be very expensive. A course of treatment can easily pass $100,000 a year to provide patients with the appropriate medications that they need.

  • 10:41:19

    ROSENBERGBut this cost problem not only applies to patients, it applies to the entire research venture as a whole. We're in a time of extraordinary opportunities to make progress, and yet our ability to do research based on the funding that's available has been flat for many years. And so many of these extraordinary opportunities, especially in immunotherapy, could certainly move along a lot faster if more funding was available to the NIH, the National Cancer Institute and other institutions.

  • 10:41:49

    REHMAll right, to Trish, who's on Long Island, New York. You're on the air.

  • 10:41:56

    TRISHHi, thank you for taking my call, Diane.

  • 10:41:58

    REHMSure.

  • 10:41:59

    TRISHThis hits very close to home for me. I lost my best friend from high school, who fought astrocytoma bravely for 12 years. I lost her in 2013. And I just wondered if the same treatment that you're experimenting for glioblastoma for would also perhaps be effective for astrocytoma, and I'll take my answer off the air.

  • 10:42:19

    REHMDr. Sampson. All right, Dr. Sampson?

  • 10:42:22

    SAMPSONSo I think it will be. It's going to depend a little bit on the particular mutations that are in a given patient's tumor, and I think that's one of the challenges going forward is to try to identify a way that is cost-effective to personalize some of these vaccines. And I think if we can do that, rather than the non-specific approach that Dr. Rosenberg agreed to or was alluding to earlier, that we can then identify approaches that are safe and potentially more effective.

  • 10:42:51

    REHMDo you want to add to that, Dr. Rosenberg?

  • 10:42:55

    ROSENBERGWell, any mutation that exists, that is any change in the base in the DNA, can potentially give rise to something new that the body doesn't recognize. And I think as Dr. Sampson has mentioned, one of the very exciting areas now of modern immunotherapy research is to identify the mutations that do give rise to a protein that's new, that the body hasn't seen before and doesn't recognize as self. And that approach of identifying those mutations and the immune reactions against them has the possibility of treating most kinds of cancers. But that's going to require a good deal of research.

  • 10:43:29

    REHMYeah, and a good deal of money. Let's go to West Bloomfield, Michigan. Lorraine, you're on the air.

  • 10:43:37

    LORRAINEHi, Diane. Thank you very much. This also hits close to home. My husband was diagnosed with metastatic melanoma last October and went through all four immunization treatments with YERVOY. And he developed -- he went through all four and developed a rash after the fourth treatment, which is pretty severe. He's very uncomfortable. Is there -- what would you recommend he could take to alleviate some of the itching and scratching, and do you have any idea how long this could last and if there are other side effects that occur after all these treatments?

  • 10:44:23

    REHMDr. Topalian?

  • 10:44:24

    TOPALIANYes, so I would really hesitate to give any specific medical recommendations without knowing a lot more about the patient, but in general, the rashes that occur with YERVOY, which is against the CTLA-4 checkpoint, or PD-1 that I was talking about earlier, these rashes are immune-based. It depends on how severe they are. Sometimes simply holding the drug for a while will lead to an improvement in the rash. Sometimes steroid medications need to be given either as a topical cream or pills.

  • 10:45:06

    REHMInteresting that these rashes become so severe that a patient is left really quite uncomfortable. Dr. Rosenberg?

  • 10:45:19

    ROSENBERGThe body can attack itself. The immune system, like every physiologic system in the body, has aspects that can stimulate it and aspects that can inhibit it, and we live in that balance. We have hormones that can increase acid secretion in the stomach, hormones that can decrease it. And the immune system is the same.

  • 10:45:37

    REHMYeah, sure.

  • 10:45:40

    ROSENBERGAnd it's this balance of inhibition and stimulation that we live in.

  • 10:45:43

    REHMAll right, to Rockford, Illinois. Hi there, David, you're on the air.

  • 10:45:48

    DAVIDHello, I wanted to pull together a few things that have come up in the show. First you mentioned that we want to use the body's ability to fight cancer. Secondly, the heart of treatment is selectivity for the cancer cell, and you've mentioned four treatment. And then there's the limitations going forward, which are the huge costs of developing genetically personalized care and so on. And then the issue of glioblastoma came up, and I was immediately struck by something else that was missing, and that is that people have used Ketogenic diets and eliminated the glucose in the diet in order to put pressure on glioblastomas because in cancer cells, the cells ferment, and they do not undergo oxidative phosphorylation properly in their mitochondria.

  • 10:46:33

    DAVIDWhich brings a question, then, if you want to select and be as clean as possible with treatment that doesn't hurt people, as the caller from Virginia wanted to suggest that, why do we not look for specifics in the mitochondrial DNA or elsewhere in the mitochondria itself and target those if we assume then that possibly the nuclear problems are downstream so-called epigenetic effects?

  • 10:47:02

    REHMAll right, Dr. Sampson, do you want to address that?

  • 10:47:05

    SAMPSONSure, so at the Preston Robert Tisch Brain Tumor Center at Duke, we are investigating a number of different avenues to treat cancer that include things, like you mentioned the Ketogenic diets. We've also looked at different exercise or quality-of-life programs to combine and provide a holistic type of treatment approach for patients with this disease. And certainly as we look towards the future, all of these therapies will really have to be evaluated in extensive clinical trials, where we really dissect out whether the particular drug is working for the patient or not.

  • 10:47:38

    SAMPSONAnd I think that those studies are now being developed for many of these types of therapies in glioblastoma. To touch on your last point, I do think that mitochondrial DNA and mutations that change the epigenetic phenomenon or the genes that modify the genes or regulate their expression is also an active area of investigation, and we've recently discovered a number of mutations that actually can change that part of the cell and are actively working to target those genes with immunotherapy, as well.

  • 10:48:07

    REHMInteresting. All right, to Dallas, Texas, Shiraz (PH), you're on the air.

  • 10:48:12

    SHIRAZThank you for taking my call.

  • 10:48:16

    REHMYes.

  • 10:48:16

    SHIRAZI'm trying to find out what would be a resource where we can find out what are the studies that are available for people to sign up. My mom's gone through breast cancer, ovarian cancer, two removals of brain tumors. She's got another operation coming up the day after tomorrow. We're trying to figure out if there are some resources. She's overseas, so, you know, all these new technologies aren't out there. So...

  • 10:48:42

    REHMYeah, Dr. Rosenberg?

  • 10:48:45

    ROSENBERGWell, a critical aspect of modern cancer research is convincing patients to enter into clinical trials that not only provide them with optimal treatment but which give us an opportunity to learn by comparing treatments which may be most effective. The National Cancer Institute has a phone number, 1-800-4CANCER, that can help inform individuals about the available trials for given kinds of diseases, and I would urge patients to seek out those clinical trials through the National Cancer Institute so that they can get best treatment, and we can learn as much as we can at the same time.

  • 10:49:21

    REHMI have an email, which asks, why can't the immunotherapy for prostate cancer be used earlier in the disease at the front end, when it's discovered on biopsy and during active surveillance, when the tumors are small and not yet metastasized? What do you say to that, Dr. Rosenberg?

  • 10:49:52

    ROSENBERGWell, many attempts at treatment prostate cancer and other cancers are applied at a time when the patient has a minimal disease burden but has a high likelihood of recurrence. And many of these immunotherapy trials, and especially in prostate cancer, are exactly that, that situation. Unfortunately, most of the vaccines don't stimulate strong enough immune reactions to manifest a change in the growth of the cancer as of yet, but I'm hoping that this kind of approach can be successful in the future. Certainly a lot of work's being done on cancer vaccines.

  • 10:50:25

    REHMAll right, and to Frank in Fredericksburg, Virginia. You're on the air.

  • 10:50:31

    FRANKGood morning, and thanks for taking my call.

  • 10:50:32

    REHMSure.

  • 10:50:33

    FRANKMy question is about the immunotherapy. Is dealing with the oncologist who usually makes that determination as to when to use it, and most oncologists will, at stage four, pretty much say there's no help and no reason to try different things. So has that been determined as to how -- what stages it can be used in?

  • 10:51:00

    REHMWhat do you say to that, Dr. Topalian?

  • 10:51:03

    TOPALIANI think that anyone who receives a cancer diagnosis, and especially stage four, after seeing their local oncologist should consider going to an academic medical center for a consultation, just to be sure that there isn't some new treatment that might not have, you know, that the news might not have reached every practitioner in the community. I think it's always a good idea to have that second opinion consultation to help put together a treatment plan.

  • 10:51:43

    REHMIt seems to me that always makes sense. Let's go now to Alan. He's in Washington, North Carolina. You're on the air.

  • 10:51:54

    ALANGood morning, Diane.

  • 10:51:55

    REHMHi.

  • 10:51:55

    ALANDelighted to be a part of the program.

  • 10:51:56

    REHMThank you.

  • 10:51:58

    ALANI wanted to share my own experience. Actually, I'm driving by Duke University, and it was 30 years ago, after having an advanced-stage melanoma removed, that I was referred to Duke to participate in some of the early immunotherapy trials there with one of Dr. Sampson's predecessors. And all I can say it was not to cure, it was hoping to cut the chance of recurrence from something around 60 to 75 percent down to around 30 percent, and 30 years later, I'm here to still talk about it. And I just want to thank all the researchers for the work they do.

  • 10:52:37

    REHMWell, Dr. Sampson, there you go with a really good news story. I'm delighted for you, Alan. You want to comment, Dr. Sampson?

  • 10:52:49

    SAMPSONWell, I think a lot of work has been going on in immunotherapy for decades now, as Dr. Rosenberg mentioned, and he certainly has been working in this field longer than almost anyone and has been pioneer -- done some pioneering research in this field, particularly in the area of melanoma. And I think we're grateful for not only the researchers who have stood it out through those decades but also to the patients that have the incredible courage to trust us to try different things. And it's so delightful to hear that so many patients now are starting to benefit so tremendously from this, and it makes our jobs a real pleasure.

  • 10:53:26

    REHMLet's find - goodness, there are so many emails here. Dr. Sampson, I want to go back to the cost question because I think there are lots of folks concerned about whether cost of these new immunotherapies because they are still under study, under development, are within reach of the ordinary person and to what extent does insurance cover them.

  • 10:54:05

    SAMPSONSo when these drugs are approved by the FDA, and as Dr. Rosenberg mentioned, more and more every day are being approved by the FDA, insurance typically will cover these treatments, and it is true that as we develop new drugs, they are expensive, but over time, as these drugs are used more and more, you see these costs coming down, and it really speaks to the overall cost of health care in this country right now, and something that I think many of us are working very hard to try to be conservative and to try to reduce costs in effective ways.

  • 10:54:37

    SAMPSONBut these drugs are extremely effective for many, many patients and provide such long and fulfilled lives that early on, I think they're still worthy of developing them.

  • 10:54:47

    REHMAll right, and Dr. Rosenberg, here's a tweet from Jonathan. Can you please discuss the potential of HIV in the treatment of cancer?

  • 10:55:01

    ROSENBERGWell, there's been some confusion about this subject. One of the ways that we introduce genes into cells is using what's called a lentivirus, which is a virus in the family of the AIDS virus, the HIV virus, but we don't use HIV at all. We merely use a modification of a similar virus to insert new genes into cells to give those cells properties that they never had and that never existed before in the course of evolution.

  • 10:55:33

    ROSENBERGAnd so we can put a gene from virtually any organism into a human cell and change its properties, and very often we'll use a lentivirus, an HIV-related virus but that can't cause the disease to insert those genes into cells.

  • 10:55:44

    REHMAnd how would that change the gene? How would it help?

  • 10:55:48

    ROSENBERGSo for example, we could take a lymphocyte out of a normal patient or out of a cancer patient, a normal cell from that patient, convert that normal cell into a cell that can attack the cancer by putting new genes into it that it didn't have before, and now we've created in the laboratory a cell that's capable of attacking and destroying the cancer once it's re-infused back into the body. And so this whole area of genetic engineering of the immune system now is a very exciting one. We basically have to create a new drug for every patient by altering their own immune lymphocytes to attack the cancer.

  • 10:56:24

    REHMThat's what's going to become more and more expensive, I would think.

  • 10:56:29

    ROSENBERGIt's actually happening. It's actually helping patients today, especially patients with lymphomas and some kinds of sarcomas, and I hope we see a lot more of it in the future.

  • 10:56:38

    REHMAll right, well, I want to thank you all for being here with us today, Dr. Steven Rosenberg at the National Institutes of Health, Dr. John Sampson of Duke University Medical Center, Dr. Suzanne Topalian of Johns Hopkins University Medicine. And thanks, all, for listening. I'm Diane Rehm.

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