Immunotherapy has forever changed the way melanoma is treated. Checkpoint inhibitors, beginning with the landmark 2011 FDA approval of ipilimumab (Yervoy®), are responsible for the increasing survival rates for patients with metastatic melanoma. Join Dr. Margaret Callahan, a medical oncologist at Memorial Sloan Kettering Cancer Center, in a Q&A discussion about how immunotherapy is increasing survival rate for patients with metastatic melanoma and how doctors are bringing the benefits of immunotherapy to more melanoma patients.
Tamron Hall: Welcome back to the 2021 Cancer Research Institute Virtual Immunotherapy Patient Summit. During this next session, we’re going to learn about the latest advances in using immunotherapy to treat melanoma, a type of skin cancer. We’re excited to be joined by Dr. Margaret Callahan, a board-certified medical oncologist at Memorial Sloan-Kettering Cancer Center, specializing in the use of immunotherapies to treat melanoma and other cancers. Dr. Callahan is also joined by melanoma veteran and immunotherapy recipient Sharon Belvin. Dr. Callahan and Sharon, thank you for being with us today.
Dr. Margaret Callahan: Thanks so much for the kind introduction, and it’s really my pleasure to be joining you all here, live today, to talk about melanoma, about immunotherapy and answer your questions. I’ll briefly just mention my disclosures here, and then it’s really my great pleasure to share the stage with Sharon Belvin, a real expert in this area and someone with personal experience as a melanoma survivor who participated in clinical trials at an early age had great success with the therapy and now has decided to give back to the community and allow us all to benefit from learning from her experience and her advice.
I’ll begin with a few brief introductory slides about melanoma, which I think as many in the audience are already aware, is one of the types of skin cancers that affect patients. Melanoma is a thought to arise from a specialized cell in the skin called the melanoma site, which gives the skin pigment, and part of the reason that we focus on melanoma in particular as a skin cancer, is that it does carry a risk of spreading or metastasizing and becoming a more serious disease.
Melanoma is described in a stage of development and in the early stages of melanoma and pre-melanoma, we primarily consider this an issue that your dermatologist might likely identify. So, for stage one and stage two melanoma, these are lesions on the skin, and they may be treated by a surgical resection, either by your dermatologist or a surgeon. In more advanced stages of disease, such as stage three disease, the melanoma may spread to local lymph nodes and may require extensive surgery, and in stage four or more advanced disease, we can see that melanoma can spread to other organs like the lung and the liver. In this situation, the melanoma is typically treated by a medical oncologist, and systemic therapies are offered, and we’re going to talk about some of these systemic therapies today. As we look at the stages of melanoma and the variety of presentations, it’s probably clear that this is a disease best addressed by a multidisciplinary team, which I have the pleasure to be a part of and getting input from dermatology, surgery, medical oncology and sometimes radiation oncology or other specialized services is all part of excellent care for this disease.
If we focus on step therapies for melanoma, what I tell my patients is that for the vast majority of patients with advanced melanoma, there are two broad categories of therapies that have shown the most activity. One category of therapy that’s shown great activity are immunotherapies, and this category can be subdivided into a number of FDA approved medications, including some medications that have been around for a very long time, like Lukin or IL-2, and some more recent medications such as ipilimumab, nivolumab and the combination of those two medications, which are amongst the most frequently used immunotherapy and therapies that offer a survival benefit for our patients. Another class of immunotherapies that is also FDA approved are oncolytic viruses that can be injected into tumors and can also cause tumors to regress or disappear.
For completeness, I’ll also mention that there are some non-immunotherapy treatments for melanoma, including a class of targeted inhibitors that work on specific mutations, which can be found in melanoma, specifically a mutation in a gene called BRAF, which is found in about 50% of melanomas. Despite these excellent therapies and quite truly, we’re lucky in melanoma to have some several excellent therapies that offer a survival benefit, the need for additional therapeutic options for patients who don’t respond to these therapies is still there. Hence, our commitment to continue working on clinical trials to develop new agents, and with that, Sharon, I think we should start taking some questions and see what the audience wants to learn about today.
Sharon Belvin: Hi, Dr. Callahan, thank you so very much for your kind introduction in the beginning of your talk today. I’m a little bit humbled over here, but I have people like you to thank for my ability to be here today. I believe that you were a fellow when I was going through my clinical trial over at Memorial Sloan Kettering, correct?
Dr. Margaret Callahan: Yeah, that’s right. That’s right.
Sharon Belvin: We’re old people. It’s OK. I would just like you all that if you did not get a chance to enter a pre-submitted question, you can still go ahead and do so. On the right-hand side of your screen, you’ll see a chat function, so that will be monitored throughout this talk. So, if you leave your question there, we’re hopefully going to get to all of them, but for those that we don’t today, we will be having answers to those on CRI website and our blog post. So just keep that in mind a little bit about myself. I mentioned that I’ve been doing this quite a long time and I was old. Well, that’s because in two thousand four, I was diagnosed with stage four melanoma when I was twenty-two. There were no young patients at the time, so I really didn’t get a chance to connect with anyone. To make a really long story short, I tried chemotherapy forever, it seems like, but it was just for a little over a year. It did not work. Finally, Jed Woolcock was my oncologist, and he said, you know, you have this opportunity to participate in one of the first clinical trials for an immunotherapy. Of course, I had no idea at all what that was, but he was nice enough to break it down for me, and it was a no brainer. I had no other options left, and this seemed almost too good to be true. But you know what? Thank God that I signed on the dotted line that day because here we are 16 years later and I get the privilege of speaking to all of you and talking to one of the physicians that help treat me all those years ago. With that in mind, we’re going to get to one of our first questions that was actually one of the more popular ones on our website, and this is, “What are some of the promising clinical trials for melanoma that are out there?” I know that you touched on part of this, but there’s a lot of stage three for melanoma patients, and they’re kind of looking on where to go.
Dr. Margaret Callahan: Sure. So, in terms of what we’ve been hearing about reported recently, I think there are a couple of especially kind of exciting developments. As you mentioned, the immunotherapies that you received fall in this class of drugs we call checkpoint blockade, and the way I think of them is as your immune system has these switches that you can turn on or off, up or down, and these drugs work by changing those switches so that that your immune system can be more on. If it’s inclined to be a little bit off and kind of turning up the volume on the immune system as it were the two of checkpoint molecules that have been targeted by drugs and are FDA approved, our PD-1 and CTL-4, but we know that there are other switches and levers that have the potential to be targeted as well, and recently we heard about a drug targeting another one of these checkpoints called LAG-3 that showed some promising activity and seem to perhaps show some improvement upon what’s already FDA approved and out there. A second group of immunotherapies that I think seem to be developing and exciting ways are a class of immunotherapies that make use of your own immune system, your body’s own cells, and do something akin to taking them out of your body, training them, sending them to school, making them extra smart, extra good fighters and then putting them back in your body, and this approach has been something that scientists and oncologists have been working on for quite some time, and I think we’re starting to get an increasing amount of data that not only can we do this, but maybe we can do this at a scale that these custom type medications could be offered to a wider variety of patients and more commonly, and then I’ll say, the last thing I’m particularly excited about is that the diversity of immunotherapies that are being tried now, I think is particularly exciting. You know, checkpoint blockade has been one really big successful avenue, but we know that it just really hits kind of one set of levers, one or two levers in the system that has hundreds and thousands of levers, and there are other important cells and other important molecules and really the city of things that we’re trying to manipulate the immune system to get it to work better for us is really exciting.
Sharon Belvin: Wow, some of that seems almost too good to be true. I wish that all of that was available to me when I was diagnosed, but along these same lines, if someone chooses to participate in a clinical trial for immunotherapy or take one of the ones that are approved, how are they going to know that immunotherapy is going to be working for them? Is there any kind of signs that are common that we can kind of look for?
Dr. Margaret Callahan: Yeah. You know, if you participate in a clinical trial, then the gold standard is going to be that you will get likely a scan, a CT scan or a PET scan before you start treatment. You’ll probably get a couple of treatments and then you’ll get another scan six to eight weeks into treatment, and those scans are going to be scrutinized by the study. Doctors and measurements are going to be made to the tumor to see if tumors to see if they’re growing, shrinking or something in between, and depending on how you’re doing on the study, you’d continue on study and another scan would be repeated at a similar interval later, and it’s really those measurements that are the gold standard as it were in terms of looking for response to therapy. But of course, we don’t only look at scans, we look at the whole patient as well, and I’ve certainly been in situations where I’ve had patients whose scans took a little while to turn around, but who felt well during therapy and sometimes felt really well during therapy in a way that we said, let’s give this a little extra time. It’s not true for everybody, but for some patients, the scans lag a little bit further behind and immunotherapy takes a little while to kick in, and if the patient is feeling well and doing well, sometimes it’s worth giving it a little more time.
Sharon Belvin: Well, that’s actually one of the bigger things that I hear as an advocate or a cancer survivor in general is that people that use immunotherapy as a treatment, they have a little bit of a lag time that’s not quite the typical that people would experience for chemotherapy, so to say, and it’s hard to be patient when you’re so, you know, gung-ho for this to work with those treatments in mind, how long does the treatment phase of things normally last, typically for a melanoma patient?
Dr. Margaret Callahan: Yeah, that’s such a good question, although it’s hard and getting harder to answer categorically because these agents have been approved for so many different types of cancers and in so many different situations. For our folks who have earlier stage melanoma that’s been removed by surgery, they might be offered one year of what I sometimes call preventive immunotherapy, and it would be preplanned that they’d get a year of treatment for our patients with more advanced disease. What I tell them typically is let’s start out by seeing if this is going to work for you and make sure that this is shrinking your tumors or preventing them from growing and that it’s not making you sick, and so we sort of make a deal. We’re going to try a couple of treatments, see if it’s working and see if it’s something that patients can tolerate, it’s not making them sick, and if we can accomplish those things, then we start to talk about how long the treatment is going to be. Obviously, if it’s not working, then it is going to be a shorter treatment plan, and if patients get sick as a side effect of the therapy, they need to change our plans as well. For those that tolerate the treatment and their tumors are shrinking. This is quite a tricky question because clinical trials had a variety of strategies in terms of the duration of treatment. Often it was a year or two years of treatment and sometimes open ended, and the FDA approval of these agents does allow us quite a bit of latitude in terms of how long to treat. But typically, we would aim for a year or two of treatment to consolidate good responses in the patient who’s responding and not having serious toxicity.
Sharon Belvin: So basically, what I hear you saying is that it’s up to your physician and you should have an open communication with them because all of this is very different no matter what patient you are.
Dr. Margaret Callahan: That’s right. I think, Sharon, you’ve cut through all of the doctor speak to the important point, which is that this is a very individual decision and a conversation that you should have with your doctor and probably when you’re going to have more than once because a lot of my patients will ask up front. I mean, how long this treatment is going to last, and I’ll say I can give you some broad-brush strokes, but we’re going to have to make some course corrections along the way, depending on how things go.
Sharon Belvin: Yes, I heard I don’t know a lot, but we’re going to take it one step at a time.
Dr. Margaret Callahan: I think that’s almost always right.
Tamron Hall: Yeah, we have a live question coming in right now, and one patient is asking, “Having completed an immunotherapy treatment in January of 2020, I’m curious about long term survival rates. Is there any data that you can share?”
Dr. Margaret Callahan: Yeah. So, yes, the data is quite promising. We have followed up extending out past five years and nearly to 10 years of survival follow up for some patients like Sharon, who were in the earliest clinical trials. We have to keep in mind that these agents haven’t been around a super long period of time, but we do have some really promising survival data, and I’d say that if you are in a category of patients who has an excellent response to therapy, including some of our patients who have something we call a complete response, then the likelihood that your response would last for years and years and years is excellent. Of course, there are no guarantees with melanoma, but for those patients who have a good response, the hallmark of immunotherapy is that those responses tend to be durable, and I think Sharon might be a great example of that.
Sharon Belvin: Yes, talk about a durable response, I’m very lucky to be here, you know, thinking about when I was treated, it almost seems like when I went back and got my initial scans done after this trial that my tumors were literally melting away. Is that kind of how immunotherapy works as it literally dissolve the tumor?
Dr. Margaret Callahan: Yeah. So, what I the way I like to describe it is, I say immunotherapy is a really unique treatment. Most of the cancer therapies we have work directly on your tumor cells. There are poison for your tumor cells. They kill your tumor cells. They do something to directly affect your tumor cells, but immunotherapy is unique. The agents that you get when you get immunotherapy actually don’t even interact with your tumor cells. What they do is they interact with your immune cells, and I talked about before that there are switches on your immune cells that can make them more activated or less activated. These hyper activate your immune cells. They get them really revved up and ready to go, and then we have to trust that your immune cells are going to find those cancer cells, attack them, destroy them, get rid of them, and so it’s a process where we’re sort of fueling up those immune cells and then trusting your immune system to do the job it’s supposed to do.
Sharon Belvin: I would like some of that rubbing up for my energy throughout the day, if you don’t mind. I’m looking in the chat right now, and actually we have one of a live question from Nancy and she asks, “I had a stage 1-A melanoma resected from my shoulder. My mother, sister and maternal aunt also had melanoma. Should I have requested a genetic study done to my tumor?”
Dr. Margaret Callahan: Right, so what I’ll say is, I mean, first of all, these are conversations where it’s really important to talk to your doctor directly and get advice from your doctor who would know all the details of your history family’s history, but when we talk about tumor genetics, there are two different things we’re talking about, and usually when we’re looking at the genetics of a tumor or one way that we look at the genetics of a tumor are in our patients with more advanced disease. We’re looking for genes that are mutated in the tumor and only the tumor things you don’t pass between family members and but that are relevant in terms of therapies and that be wrapping patient was an example of the tumor genetics. In your case, I think what you’re thinking about is, is there something that’s in your family that is putting you at higher risk of having a melanoma? We do know that, first of all, if you’ve had a melanoma yourself, you’re at higher risk of having another melanoma. So, you’re going to want to make sure that your dermatologist is aware of that history, and if you have a first degree relative who has a melanoma, likewise your risk is a little bit higher, and so making sure that you’re having those conversations with your doctor and getting good dermatologic follow up, which I’m sure you are, it’s going to be an important part.
Tamron Hall: You know, that brings up the question, “What is the difference between genetic testing and genomic sequencing?” because I don’t even know this and I’ve been in this arena for a while.
Dr. Margaret Callahan: Yeah, I think those phrases are thrown around in different contexts and mean different things to different people. For those of us who work more often with patients with advanced cancer, we talk about genomic sequencing or actually the process of sequencing or determining and looking for the mutations in a patient’s cancer. That that’s what the sequencing does. By looking for that sequence, we can tell if there are any mistakes in the genetic sequence of the tumor. So that’s the genomic sequencing, and then genetic testing is often used. It’s applied to different settings. Sometimes it means we’re sequencing your tumor, we’re doing genetic testing on your tumor, but sometimes it means we’re doing genetic testing on you. Do you have any genes that you could pass on to family members that your family should know about and might change your risk of different cancers, or put you in a category where you should have different types of screening? Sort of like I think a lot of folks are familiar with Angelina Jolie’s family history around breast cancer.
Sharon Belvin: Yeah, that’s all very, very exciting. I should probably have some of that done considering I have children. We have two questions that kind of go back to back with this. I’m going to back step a little bit and say, can you kind of elaborate on what the common side effects are of immunotherapy? Is there a way that you can kind of categorize that?
Dr. Margaret Callahan: Sure. So, we talked about already that immunotherapy doesn’t directly kill your cancer cells, it doesn’t directly attack the tumor. It works on these switches, on the immune cells, and we’re kind of try to boost your immune cell when we boost up your immune cell. We hope that your immune cell takes that extra energy and focuses on those tumor cells. That’s really the job we want it to do. But we also know that the immune system might choose to do some additional or other things while it’s so activated and those extra things that the immune system does can hurt your normal tissue. Your non-tumor tissue, and that’s really the underlying reason for all the toxicities that we see with immunotherapy. So, I say common toxicity, itchy skin, and that’s like your immune system going into your skin and having a little party there and making you so itchy achy joints. Same thing. It’s the immune system irritating those joints and throwing them out of whack, and luckily for the vast majority of patients and side effects, we’re able to sort of fine tune the immune system. There are medicines that can calm it down a little, take it down a few knots and let those side effects allow patients to recover from those side effects.
Sharon Belvin: That leads right into the next question that we have from one of our live listeners and this one says, “I have melanoma and have received three immunotherapy treatments. I have severe side effects from treatment and my doctors are unsupported in reducing or managing my side effects. Because scans show no more cancer, I’m feeling debilitated. What should I do now?” That’s kind of a heavy one.
Dr. Margaret Callahan: That is kind of a heavy one, I mean, I think that this goes to making sure that you’re having those close conversations with your doctor, which it sounds like you are making sure that, you know. They know how you’re feeling on this therapy and that they’re hearing the impact this is having on your life, and you know, I will say not knowing the specifics of your situation, but that of course, side effects to immunotherapy can be quite debilitating, quite serious, and occasionally, it’s helpful if you feel like despite having excellent communication, that your concerns aren’t being addressed. Sometimes it’s helpful to get another opinion, another set of eyes on the situation, and because we’re aiming not just to treat your cancer, but to treat you and make sure that you feel well while you’re getting this treatment. Sometimes there are bumps in the road, but we should always be working to kind of optimize how you’re feeling throughout that treatment.
Sharon Belvin: Yeah. You know this next question. There are so many of them pouring in about treatment side effects, so we could go on and on with that forever. So, I’m going to leave that for the blog at the end. Maybe you can get to those, but one of the questions that just popped up was one that I actually get asked a lot from new cancer patients and this one’s from Irene, and she says, “I will be going to a medical center to discuss enrolling in an immunotherapy clinical trial. What questions should I be saying in this meeting?”
Dr. Margaret Callahan: Well, so participating in a clinical trial is an exciting opportunity, but it has to be, you know, it’s a very personal choice. So, I would make sure that you understand clearly, what are your alternative options, what are the choices that you would have in terms of standard treatments? Why is the clinical trial a good option in the context of what other choices you have? Then I would make sure that I asked some very specific questions about what’s involved in participating in a clinical trial. How many visits, how long are the treatments? What are the complexities of being involved in a clinical trial? Because I’m sure as Sharon recalls, sometimes it’s quite involved and there are a lot of visits and a lot of extra procedures, and you need to make sure that you kind of walk into it well- educated and with open eyes. Those I think those are the biggest questions that I would ask.
Sharon Belvin: Well, those are all fantastic and extremely helpful, so I thank you on behalf of the patients. You know, as kind of a wrap up question here, I wanted to ask, “How has immunotherapy changed your outlook on cancer care?” because I can only imagine going as a patient perspective, the words that were said to me when I first went to see Dr. Walsh as to the words that you would say now to a patient that walks into your office.
Dr. Margaret Callahan: Yeah, I mean, as Sharon knows, my personal history with immunotherapy is that I started at Memorial Sloan-Kettering about 10 years ago, give or take, and while I was a trainee, we saw some of the very first big successes for these checkpoint blocking antibodies in clinical trials. It was tremendously exciting and it really transformed my little niche of oncology melanoma, and we went from having therapies that were pretty crummy to therapies that had response rates above 50 percent and were just lifesaving medications, and it’s been extremely gratifying over the last 10 years to see more and more having access to these therapies, expanded use of these therapies and new opportunities.
Sharon Belvin: Well, you know, I can’t say the words thank you enough. I feel like those are so inadequate. I wish that there was something more that I could say because as a cancer patient that was thinking that they were going to die to a person who was sitting in front of you or in front of you sixteen years later, the words are, I’m laughing, so truly thank you on behalf of all of the patients for the information that you gave today, it was extremely helpful for those of you online that didn’t get your question answered today, no worries. They will be fielded by experts on CRI’s home page on a blog section, so just staying tuned for that and you should have seen a poll question pop up. We would love to hear your answers to that. Thank you all so much for your time today and have a great weekend.