Talking to Your Oncologist about Cancer Immunotherapy

When do most patients first learn about immunotherapy? How long can you start after your initial course of treatment? How does it feel to take part in a clinical trials? How do you anticipate and manage side effects? 

In this webinar designed for patients and caregivers, Ariella Chivil, a patient advocate, and Alexander M. Lesokhin, MD, her oncologist, discuss the nuances of communicating and informing both doctor and patient while on immunotherapy. They share their experiences with immunotherapy and answer viewer questions.

Ariella Chivil was diagnosed with Hodgkin lymphoma in 2010, just before her junior year of college. After completing 14 different treatment protocols, each with its own set of side effects and complications, Ariella and her doctors decided to try something new: a clinical trial of the immunotherapy nivolumab (Opdivo®). Her first scans after beginning the trial showed a marked reduction in her tumors. In May 2016, nivolumab received FDA approval for the treatment of Hodgkin lymphoma. Today, Ariella is off treatment and enjoying living and working in New York City.

Alexander M. Lesokhin, MD, is a hematologic oncologist at Memorial Sloan Kettering Cancer Center who specializes in treating people with blood cancers such as lymphoma and multiple myeloma. Specifically, he’s focused on developing innovative ways to use the immune system to treat cancer and help these patients. To this end, he’s currently leading two phase I clinical trials that are evaluating different immunotherapies in patients with advanced blood cancer, and is also a co-investigator in two other immunotherapy clinical trials. In addition to his clinical immunotherapy expertise, Lesokhin’s laboratory research aims to characterize a subset of immune cells called myeloid-derived suppressor cells (MDSCs) and how they influence the development of adaptive immune responses against tumors.

The "Cancer Immunotherapy and You" webinar series is produced by the Cancer Research Institute and is made possible with generous support from Bristol-Myers Squibb, with additional support from Regeneron, Sanofi Genzyme, and Adaptimmune.

Browse our Cancer Immunotherapy and You Webinar Series playlist on YouTube or visit the Webinars page on our website to see other webinars in this series.

Webinar Transcription

Brian Brewer:

Welcome to the Cancer Research Institute “Cancer Immunotherapy and You” webinar series. Today is Tuesday, June 19, 2018. The title for today’s webinar is “Talking to Your Oncologist About Cancer Immunotherapy.” Before we begin, I’d like to thank our generous sponsors who have made this webinar series possible: Bristol-Myers Squibb, with additional support from Regeneron, Sanofi Genzyme, and Adaptimmune.

My name is Brian Brewer and I’m director of marketing and communications at the Cancer Research Institute, a nonprofit organization founded 65 years ago with a singular mission to fund lifesaving immunotherapy research to develop treatments that harness the immune system’s power to fight all cancers. This work has contributed to the development of immunotherapies for a variety of cancer types.

We present this webinar series to patients and caregivers to help them understand what immunotherapy is and how it is different from other treatments, to provide information on the latest developments in research and treatment, and to connect patients to immunotherapy clinical trials. Our website, www.cancerresearch.org, features these and other resources for patients and caregivers as part of the Cancer Research Institute Answer to Cancer patient education programs.

Here you can read or watch stories shared by others who’ve received immunotherapy treatment, register for one of our Immunotherapy Patient Summits, browse our entire library of past webinars featuring the world’s leading immunotherapy experts, access information on other resources including treatment, emotional support, and financial assistance, and find help locating an immunotherapy clinical trial.

June is Cancer Immunotherapy Month. During the month, we’ve planned 30 days of educational content including coverage of the latest breaking news from the world’s largest oncology conference, immunotherapy patient video stories, our Wear White Day social media campaign, and more. Check out all the exciting activities at cancerresearch.org/june.

And on Saturday, June 30, we’ll be kicking off our Immunotherapy Patient Summit series in San Francisco. At this free half-day event, we connect patients and caregivers with immunotherapy experts to discuss the latest advances in research and treatment. Other summits are scheduled for New York City, San Diego, and Houston. And we have a Livestream broadcast as well if you’re unable to attend one of those markets. Go to cancerresearch.org/summit to learn more.

Now, it’s my pleasure to introduce today’s speakers—Ariella Chivil and her oncologist, Dr. Alexander Lesokhin. Ariella was diagnosed with Hodgkin lymphoma in 2010 just before her junior year of college. After completing 14 different treatment protocols, each with its own set of side effects and complications, Ariella and her doctors decided to try something new—a clinical trial of the immunotherapy nivolumab. Her first scans after beginning the trials showed a marked reduction in her tumors. In May 2016, nivolumab received FDA approval for the treatment of Hodgkin lymphoma. Today, Ariella is off treatment and enjoying living and working in New York City.

Dr. Lesokhin is a hematologic oncologist at Memorial Sloan Kettering Cancer Center, who specializes in treating people with blood cancer such as lymphoma and multiple myeloma. Specifically, he’s focused on developing innovative ways to use the immune system to treat cancer. To this end, he is currently leading two phase I clinical trials that are evaluating different immunotherapies in patients with advanced blood cancer and is also co-investigator in two other immunotherapy clinical trials.

In addition to his clinical immunotherapy expertise, Lesokhin’s laboratory research aims to characterize a subset of immune cells called myeloid-derived suppressor cells and how they influence the development of adaptive immune responses against tumors. Ariella and Dr. Lesokhin, it’s an honor to have you both here with us today, and welcome.

Ariella Chivil and Alexander M. Lesokhin, MD:

Thanks for having us.

Brian Brewer:

Ariella, why don’t you tell us what was going on in your life when you first met Dr. Lesokhin? And what was this experience like for you?

Ariella Chivil:

I met Dr. Lesokhin in 2013 after I had exhausted all treatment options available to me at that time. I had been diagnosed in 2010 and I had gone through about 14 different protocols before meeting Dr. Lesokhin, including a pretty noxious chemotherapy protocol called C-MOPP, which had been marketed to me as a last resort.

In the morning I met Dr. Lesokhin, I had commuted all the way from New Jersey to the Upper East Side, about 12 hours, after returning home from a two-week hospital stay. I had just been in the hospital due to a lymphoma-related complication. I required bowel surgery, a liquid diet, and I had just learned through some scans related to this surgery that my cancer that we thought had been eradicated by C-MOPP, this last-resort drug, had in fact come back and was growing really quickly.

When I showed up that morning after being in the hospital for two weeks and feeling really weak, I was like a shriveled, bald, green tin shell of myself. So I really appreciated the warm, comforting vibe the Dr. Lesokhin’s team put out there because I definitely needed it after the whirlwind I’d been through.

Brian Brewer:

Dr. Lesokhin, what was Ariella’s state of health like when you first met her? And what was that experience like for you?

Alexander M. Lesokhin, MD:

I think one word that would summarize it would be horrible. I mean, I think she was quite ill at the time as she so eloquently described just now herself. It was pretty clear that her disease was rapidly progressing. And that it was affecting sort of vital organ function in some ways.

And in many ways, it was rather, I think, fortunate and maybe lucky that her organ function remained good enough for her to be eligible to enroll in a clinical trial. I think it speaks a lot to the human condition—that capacity to tolerate significant challenges to physiology.

Brian Brewer:

So Ariella was enrolled in a clinical trial testing and immunotherapy as I mentioned, nivolumab. How did you describe, first, the concept of immunotherapy to Ariella?

Alexander M. Lesokhin, MD:

So this is about five years ago now. I think one thing that I tend to do—I take what I do quite seriously. But I tend to be a little goofy when I’m talking to patients just because it’s a stressful situation. So I can’t recall exactly the extent of my goofiness at the time and how I presented things to her. But in general, the approach that I take is to explain—or that I took and I still continue to take in the context of these times of immunotherapies—is to explain that we’re not really targeting the cancer cells specifically. At least, that’s not what we think we’re doing. The reality is that, in many ways, we know something about what we’re doing. But in many ways, we also don’t know of some things we’re doing. That’s the nature of clinical trials in general.

So I explained that we are trying to positively affect the way the patient’s immune system is interacting with their cancer. By positively affect, I mean to try to enable someone’s own immune response to treat them and eradicate their disease.

Brian Brewer:

Ariella, had you ever heard of immunotherapy before meeting with Dr. Lesokhin? And what were your initial impressions of the idea?

Ariella Chivil:

Great question. So I had initially been “pitched” on this trial during that hospital stay right before I met Dr. Lesokhin. Dr. [Matthew] Matasar, who is my primary oncologist, initially ran through the idea by me. He talked about how great Dr. Lesokhin was and thought we’d be a good personality fit, which makes a lot of sense now. And he explained that it would help my immune system kind of fight back.

But it wasn’t until a meeting with Dr. Lesokhin and sitting down with him and going through some of his anecdotes and doing it in his particularly goofy way that I really grasped it and understood the potential that there was for it to help me. I think, for me, when I had that conversation, I had been so used to a lot of chemotherapy drugs, a lot of things that were more of a shock-and-awe approach.

So the idea that there is a drug that wouldn’t be wiping out all my bodily systems and would, in fact, be helping my immune system do its own job and combat the cancer was really appealing to me. It’s like, OK, I get to be my own superhero.

Brian Brewer:

How did you explain to Ariella what PD-1 checkpoint blockade is and how it works?

Alexander M. Lesokhin, MD:

So I mean I think I generally—again, I’m going to say that I don’t remember exactly how I explained it to Ariella because I’ve got a few gray hairs you can probably see here, and I get a little senile. But in principle, I basically explained the concept that, when immune cells become activated, specifically T cells—those are the cells that we think we are targeting with PD-1 blockade—when T cells see an antigen, when they see what their target is, they generally display things on their surface that let the immune system and other cells around them know that they’re activated. They’ve seen something. And that it’s the job of the other tissue cells to basically inform the T cell whether they’re good or bad. And they do that by trying to trigger this PD-1 signal on T cells to sort of say, hey, I’m OK, [don’t attack me].

And the purpose of PD-1 blockade is to interfere with this, hey, I’m OK, signal. As it turns out that cancer is—and actually, Hodgkin lymphoma is really an outlier in cancer—can upregulate the triggers for PD-1. It’s called PD-L1. And Hodgkin lymphoma is actually, it turns out, quite a major outlier here because it really uniformly highly over-expresses this PD-L1 trigger that is a negative regulator T cell response. So PD-1 really is something that interferes with that and allows for the immune cells to attack the cancer cells.

Brian Brewer:

Ariella, if you are talking to a patient who is considering treatment with PD-1 blockade, how would you describe the therapy?

Ariella Chivil:

I think I would describe this therapy as an opportunity to help your own immune system do the job it’s designed to do. And that when you have cancer—and particularly, if you have refractory cancer [cancer that is no longer responsive to treatment], which is what I had—your immune system gets beaten down. It gets tricked by the cancer cells that have various ways of avoiding detection, which prevents your immune system from finding them and killing them. So there is this drug that kind of gives you a little booster shot and lets your immune cells do a better job of finding, identifying, and attacking cancer cells without some of the quality-of-life hindrances that you might have with other drugs.

So I would say, it’s an opportunity to have a protocol that gives you quality of life and makes it easier to heal yourself and not have to worry about some of the side effects you might typically associate with a cancer drug like nausea, weight loss, hair loss, things like that.

Brian Brewer:

Is there anything, Ariella, that you now know about treatment with checkpoint blockade that you wish you had known at the very beginning or something that you’d like to share with a patient who’s considering treatment?

Ariella Chivil:

It’s been only five years out for me. So I think it’s kind of difficult to tell now what a long-term impact will be, if any. But I think the very thorough and in-depth approach that Dr. Lesokhin and his team took with preparing me for the trial and checking in with me during the trial and during the follow-up phase hopefully helped set the table for me and helped me figure out what I should be looking out for in the future when it comes to things like side effects.

I feel pretty prepared. And I think it also helps that I’ve had a very smooth handoff and transition to following up with my primary oncologist. I have this safety net of sorts. I know that, if anything does happen with this drug, we will quickly be able to identify it and do something about it. And I will have the full support of the Memorial Sloan Kettering team, whether that’s on the therapy side or the lymphoma side working together to help.

It’s really important to make sure that, when you do select a clinical trial or select a drug, you also are selecting the right care team for you so that you can feel comfortable communicating your symptoms with them, so you can feel comfortable reaching out to them when you have a question or when things seem even slightly awry. The sooner that you can address something, the better.

Brian Brewer:

So speaking of that, did you experience any side effects from treatment?

Ariella Chivil:

When I first came into this not knowing what to expect, I was definitely expecting some of the traditional side effects I had had from different treatments. And when those didn’t happen, I was a little concerned. I was like, I’m not feeling nauseous. Does this mean it’s not working? But I know I felt tired naturally. That was, I think, the first thing I noticed. There was definitely some fatigue there just from feeling super weak as my baseline and commuting into the city, going to the treatment, being there for several hours, and coming back.

I think I had pneumonitis at one point. And there may have been some other minor side effects that we took in stride. And I think what was really neat about this particular experience—because I was one of the first people with lymphoma to receive this drug in this particular trial—we had a very collaborative approach to problem solving and figuring out what to do when symptoms came up and how to manage them. So I felt very empowered to participate in these decisions and figure out what was best for me and how we should continue the trial and how we should manage some of the minor bumps along the way.

Brian Brewer:

So five years ago when you got treatment, the side effect profiles in checkpoint blockade weren’t as well understood as they are today. Dr. Lesokhin, a question for you—how do you bring up the topic of potential side effects? And what is very important that a patient needs to know about side effects on immunotherapy?

Alexander M. Lesokhin, MD:

With these kinds of therapies—and PD-1 is one of them—it’s certainly the furthest advanced in terms of development and one that’s had the most clinical efficacy to date. But it’s one of a family of new treatments. In general, this family of treatments is designed to disinhibit the immune system, what Ariella was just talking about, where it gives you this kick or this boost. Really, it releases the brakes on the immune response.

And the hope is that this allows the immune response to be refocused onto a patient’s cancer. But there is potential because we are interfering with sort of normal homeostatic mechanisms, normal ways that your body regulates itself, that you will have an immune response against your own tissues and organs.

And that can be quite diverse in its presentation. Ariella mentioned a little bit of pneumonitis, which fortunately in her case was just a little bit. But we look out for, and are very in tune with, any organs that your immune system surveys, and when we’re interfering with these normal mechanisms of immune control, any organ can be affected.

At the time when we were beginning this treatment, Ariella was the first patient I treated with Hodgkin lymphoma—or maybe the second. But anyway, she was definitely one of the first. And we didn’t know what the specific side effects might be and if there was potential here for specificity in the kinds of side effects that we might see in someone with her type of cancer as opposed to somebody with, let’s say, melanoma or lung cancer or one of the other cancers where these drugs were being very actively investigated at that time.

But we did have a general sense of what types of side effects exist and a general sense—and actually, a pretty good sense—for how to manage them together with the patient. And I think one of the key messages in my discussions with her and with essentially all the other patients that I see on these clinical studies is to make sure to explain this concept that we are really releasing the brakes. And it’s systemic.

And to also make sure that patients are very well aware of how to reach us, very well aware that, should anything happen that’s a little bit abnormal, it’s always much better to give us a call, to let us know, to let us evaluate, even if it’s just over the phone, what is happening so that we can provide some guidance and reassurance about whether this is important or not important, et cetera.

Because, really, the one thing that we have seen and I have the benefit of hindsight is that the sooner we address any side effects, the less severe that side effect is.

Brian Brewer:

Ariella, you mentioned earlier that it was important to choose the right care team. So that leads me to think, it wasn’t just Dr. Lesokhin that you interacted with on this trial. Who were some of the other people that you interacted with while receiving treatment?

Ariella Chivil:

For me, when I was going through treatment, I think there is an entire service design approach that Memorial Sloan Kettering takes when it comes to patients coming in, whether they’re coming into the facility for the first time and meeting everyone or they’re an old patient that’s coming in and meeting new folks. From the very moment I walked through the door, there’s a greeter, then the person at the front desk. And there’s folks working at reception that you come to know over time. Everyone is super friendly and welcoming and answers every question. There are also several nurses I worked with through Dr. Lesokhin that I could text if anything ever came up, folks that would always check in on me and really make me feel like anything that I had to share was worth discussing and that I was empowered to identify when something may be slightly off. As Dr. Lesokhin mentioned, being able to share those things with candor is really important.

So I felt really grateful that I was able to have such a strong rapport with so many people on Dr. Lesokhin’s team, who really made me feel comfortable sharing these sometimes rather uncomfortable parts of your body. When your body starts to kind of work against you—especially certain organs—it’s kind of uncomfortable to talk about. And it’s really important that you have people you feel comfortable sharing those things with and that you can trust and that won’t make fun of you for saying that maybe you are going to “shit your pants in the subway.” These are things that you got to feel really comfortable talking about.

Brian Brewer:

You said that when you started your treatment you were expecting to experience some of the traditional side effects. And when you didn’t, you became worried that the drug wasn’t working. When did you know that something was happening, something good?

Ariella Chivil:

What was really neat about this drug is that we noticed that things were working at around the first scan. I remember going into that appointment after just having that scan and talking to Dr. Lesokhin. And I think he was like, so I think I have some good news for you, in a very chill way that he does where he’s not going to oversell it. He’s not going to overhype it.

He kind of sneaks in the good news, which I appreciated, because I think there was this approach where it’s like, yes. We have this initial positive response. And that’s great. But let’s keep working. Let’s keep getting the drug. Let’s keep seeing how this will unfold. And that’s the exact mindset that I adopted. While it was great to have that initial success, I had had initial success in other drugs as well that ultimately ended up not panning out for me. So I think every time I came in to receive their results of a scan, the more confident I felt.

And even now when I go in for follow-ups, I know it continues to work because, even now, five years later, going in for a scan, when I hear those results, I’m like, OK, still good. I think that’s how I’m going to continue to operate as long as this keeps going.

Brian Brewer:

Dr. Lesokhin, what was that experience like for you to see one of your first patients treated with checkpoint for lymphoma respond so well?

Alexander M. Lesokhin, MD:

It was incredible actually. As Ariella pointed out herself, when we first met, she was quite ill. I actually hadn’t seen her stand up until maybe two or three weeks later. And I mean, to me, it was pretty apparent that something good was happening even before this scan. It was one of those remarkable kind of experiences that you always hope for when you’re testing new drugs and doing early-phase clinical studies. Nothing but good.

Brian Brewer:

Was it a typical response that you’ve seen now in the following five years? Or what’s the percentage of Hodgkin lymphoma patients that respond to checkpoint blockade?

Alexander M. Lesokhin, MD:

In follow-up studies, it’s been around 65% of patients that respond. In this trial, it was 87%, which it’s a small trial, so it’s hard to know. I think the follow-up larger numbers probably are more accurate. So it’s a 65% to 70% of patients that do respond, which is really remarkable because I think there is a lot of excitement around PD-1 blockade.

But unfortunately, many other malignancies, the response is, although they’re very durable and they’re not associated generally with a tremendous amount of standard chemotherapy-related side effects as Ariella described—the responses are more in the 20% to 30% range. So really, Hodgkin lymphoma is quite an outlier. And I think it’s, in part, because of this significant and relatively uniform overabundance of this PD-L1 signal on malignant cells.

So it’s the biology of the actual malignancy that it turns out is what makes it so susceptible to this treatment. Although a priori, we have no idea it was going to be that susceptible.

Brian Brewer:

That’s good news for patients. What happens when a patient doesn’t respond? What’s the next step after checkpoint therapy?

Alexander M. Lesokhin, MD:

Yeah. So that’s difficult. And I think this applies actually to many clinical trials. When patients don’t respond, basically, you can’t continue the study that isn’t providing any benefit. So you have to look for alternative treatment approaches. And in the setting of post-PD-1 therapy, I think, in Hodgkin lymphoma, I think it’s quite challenging in terms of what to do next.

And it has to be really a patient-specific discussion and decision point because there’s a lot of things that go into that. What were the prior treatments to date? What’s the current overall clinical status? How ill is the patient? And what are the available treatment options, both experimental and standard?

Brian Brewer:

What actually is the actual FDA approval status of the drug that Ariella received? Is it given as a frontline therapy? Is it given following prior treatment?

Alexander M. Lesokhin, MD:

It’s given following prior treatment. It’s approved for individuals that have received prior Rituximab, as well as prior stem cell transplant. There’s a warning in terms of use of the drug around the time of allogeneic transplantation.

Brian Brewer:

Can you describe what allogeneic transplantation is?

Alexander M. Lesokhin, MD:

Yeah. It’s something we discussed with Ariella a few times actually.

Ariella Chivil:

Yes. Batted that off, thankfully.

Alexander M. Lesokhin, MD:

Allogeneic transplantation is, I would say, an older form of immunotherapy. Or maybe that’s not quite accurate to say it’s older. But it’s basically when we match the tissue type of the patient to another individual. And then the patient, following some conditioning treatment, receives that other person’s stem cells, inclusive of the immune cells that that individual has. And the idea is that the other patient’s immune system is not tolerized to the recipient patient’s malignancy, and therefore will see that cancer as a foreign bad thing that needs to be removed.

The downside is that donor’s stem cells and T cells and B cells can also see the recipient patient as not themselves and attack the patient’s organs as well.

Brian Brewer:

Ariella, at the time that you received this therapy, you were pretty much well-versed in what clinical trials are and the things to consider about them. What would you say to someone who’s never experienced a clinical trial? And in fact, we’ve met a lot of patients who don’t even know what clinical trials are or that they exist as an option.

Ariella Chivil:

Think of [clinical trials] as just as valid an option as any other protocol that’s in the standard of care. And it’s worth exploring with the support of your physician. I would recommend educating yourself about all the options available to you. There are a lot of experimental drugs out there, some that may be a better match for you and the current state of your life and your current health profile.

I would recommend joining patient support groups, perhaps, to get some anecdotal evidence around side effects and where people have received care. I would recommend going to clinicaltrials.gov. And I would really recommend sitting down with your physician and asking as many questions as you can to feel comfortable.

And I would also look at it as an opportunity to not only know help yourself in finding a treatment that might work for you that you haven’t explored before. But you’re also really helping so many other patients out there who may potentially benefit from this drug once it comes to market. And you’re helping to move science forward.

Alexander M. Lesokhin, MD:

I would second everything you have said. I would also say that it’s important for people to recognize that there are different kinds of clinical studies. There are the types of clinical studies where a new drug is being tested to identify a safe dose. And so this is a phase 1 study. There are studies where a safe dose has already been identified and one asks, does this drug have any effect in this disease that’s potentially meaningful relative to historical experience? That’s typically a phase 2 trial.

And then there is the gold standard phase 3 trials where one evaluates whether your candidate drug is better than the standard of care that’s on the form. So all of these different trials have different pros and cons. I think they’re all very, very important for the development of new treatments for patients. And I think all patients should consider them as an option as Ariella noted that can be used in addition to standard-of-care treatment approaches.

Brian Brewer:

Thank you. You two have a great rapport. It’s obvious that you have a great doctor-patient relationship. Ariella, is that a consequence of being on a trial and staying in that trial and on study and going back for these scans? Is this atypical of the experience that you had with other oncologists who treated you?

Ariella Chivil:

I mean, obviously, Dr. Lesokhin is the man. It is known. No, I mean, I think I’ve gotten really, really lucky having spoken to dozens of other patients that have been in other treatment facilities across the US and around the world. I think Memorial Sloan Kettering hires great people, Dr. Lesokhin being one of them and Dr. Matasar, my primary oncologist, being another.

And I think that’s really spoiled me. I think I’ve really—my view has been colored by them and the wonderful experiences that they had with both of them and their teams. I think Dr. Lesokhin and I, we’re also able to develop such a great rapport because he helped me during such a difficult time in my life and had the exact right temperament that I needed after going through so many different protocols, feeling very discouraged, and kind of felt like some of these promising drugs just weren’t going to ever work for me.

He kind of came in there and was like, yeah, let’s try it. Why not? Let’s give it a go. Let’s see. I think that was exactly what I did at that point in time. And he really met me where I was on my sickest days or on my healthiest days, on my saddest days, and on my happiest days.

And I think that’s really how we were able to develop such a strong relationship, that I didn’t feel like I had to pretend to be anyone else when I walked in that room with him or with his team. I could be myself and share whatever experience I had with the drug—good, bad, ugly—and they were going to coach me through it.

Brian Brewer:

That’s fantastic. We are almost out of time. And I wanted to give the viewers an opportunity to ask questions. So if you’re watching this, you should see a Q&A box on your screen. And you can type a question into that. And we’ll try to get to as many questions as we can. We have a question from Cynthia saying that she’s been off immunotherapy for 10 months. Did you have, Ariella, any late side effects after your treatment with nivolumab?

Ariella Chivil:

Let me think. I don’t believe I did. But that was definitely something that we closely watched and guarded against. For me, I think the fatigue, which could have just been a result of the cumulative side effects of all these different treatments that I had had, and some of the scar tissue in my system, other remnants of the lymphoma in my body that contributed to this. So I think those were things that impacted my ability to live a full life initially.

But I do think that, as I moved off the therapy and continued to have follow-up treatments and continued to monitor, I started to feel more and more comfortable. I started to have the trappings of a normal life. I started working, moved out of my parents’ house, and started to develop some more independence. So we’re still watching certainly. And I have them on speed dial in the event that anything weird happens. So that makes me feel really comfortable knowing that I have that in my back pocket.

Brian Brewer:

Good. Dr. Lesokhin, this is more general immunotherapy question. Is immunotherapy being used as a firstline therapy for any cancers at this time?

Alexander M. Lesokhin, MD:

Yeah, actually. It’s approved as a firstline therapy for melanoma. Actually, a combination of immunotherapies approved and formed the combination of PD-1 and CTLA-4 blockade. It’s also approved as a first line in lung cancer. And it’s being investigated in Hodgkin lymphoma earlier in the disease’s natural history as well.

Brian Brewer:

We have another question from Cynthia. Of the other patients that participated in Ariella’s trial, what’s the percentage of those that are also five-year survivors?

Alexander M. Lesokhin, MD:

Yeah. This data needs to be updated actually. I don’t know that answer. Hopefully, it will be soon. I would say that of the patients that I treated that Ariella is not alone.

Brian Brewer:

We have a question from Rada. What was the informed consent process like? How long did it take? Did you understand what you were being given, Ariella?

Ariella Chivil:

That’s a fantastic question. So anyone that’s going through a clinical trial or has heard of them, just to give some background. Typically, it’s just like a stack of papers written in 12 point, Times New Roman font. And you’re typically not in the mental state to go through however many pages there are and properly understand, line by line, what to expect and what’s going to happen to you.

The nice part was Dr. Lesokhin’s team—I remember one of the first nurses I worked with sat with me and went through all the pages with me and paused and let me ask questions and explained things in layman’s terms and made me feel a bit more in control of the situation and let me know that, you know, there are certain choices. Like there are certain things I could sign off on and other things I did not have to sign off on.

She let me know what was optional and what was required dependent on how I was feeling and my particular schedule that I was in that point in time of my life. So that felt really good knowing that I had the information in front of me, there were some choices that I could make, and that I was going into this with open eyes.

I will say, ultimately when I was starting this trial and deciding to participate and receiving this drug, there were no other options available to me at that point in time. So I was going to run with it probably regardless to be honest with you. I was willing to accept that risk at that point in time in my life. I know I was young. I wanted to exhaust all options available to me.

And whatever side effects that came, I just had this mindset that, eventually, science will catch up to helping me deal with that side effect if there wasn’t something available then and that I’d be lucky to live long enough to experience those side effects and deal with them as a normal person. So it’s not the mindset that everyone is going to be in when they’re going into a clinical trial. And it’s not the best approach for everyone in that phase of their life. But that was the decision I made. And that was the cost-benefit analysis that I made going into it.

Brian Brewer:

Dr. Lesokhin, we’ve talked a lot about the particular drug that Ariella received. But there are actually a total of five approved drugs that work on that same pathway, that PD-1 pathway. And we have a question from Bob about differences. Do they work differently? Do they have different side effects? Or are they better in some cancers than others?

Alexander M. Lesokhin, MD:

Sure. So certainly, they are better in some cancers than others. We sort of touched on the fact that, in Hodgkin lymphoma, it’s really quite a bit of an outlier in terms of its efficacy. In terms of the different agents, I think they all sort of target the same pathway, the same interaction. There probably are subtle differences between them. In general, it’s the biology of the way a patient’s immune system is interacting with their cancer.

Brian Brewer:

Thank you. And we have time for one more question. This one is from Gina. She asks: when you’re diagnosed with cancer and you’re asked for a biopsy where they take tumor tissue out of you, do you need to specifically request that that tissue be sent for genetic typing to get a better understanding of the tumor and whether or not you can see signals of likelihood that a person is going to respond to therapy or not? Or is this something that’s just done as a matter of course? I’ll throw that at Dr. Lesokhin.

Alexander M. Lesokhin, MD:

I don’t know to what extent it’s done as a matter of course. Here [as MSKCC], it generally is. I think that is incredibly valuable, and very important to do because we know that one of the mechanisms by which individuals respond is through the presence of mutations within their cancer, with the mutation being changes in the DNA that affect the things the cancer cell presents. And these things are so-called neoantigens.

And the more mutations someone has, the more likely it is that they have a relevant molecule or relative change in their genetics that allows for better presentation and for immune recognition to occur. And it’s actually been shown in now several translational studies that the quantity of mutations that a cancer has is related to responsiveness to treatments for this disease.

And the FDA has recognized this because they have allowed for the use of one of these agents in patients with something called mismatch repair deficiency. And this is a type of malignancy that has many, many mutations and is very likely to respond to these agents. And so that’s kind of the first biomarker, if you will, that is disease agnostic. So anyone with this mismatch repair deficiency, irrespective of what kind of malignancy they have is eligible to receive immunotherapy.

Brian Brewer:

Do you see this kind of mutation in breast cancer?

Alexander M. Lesokhin, MD:

I’m not a breast cancer specialist. So I couldn’t tell you what the frequency is. I think this is a type of mutational profile that has been best characterized in colon cancer. It is present in some gynecological malignancies. I don’t know off the top of my head if there’s a rate of presence for this mutation of this deficiency in breast cancer. But I would guess that there probably is. But that’s a guess.

Brian Brewer:

One of the other things that immunologists look at is the amount of T cells that have already infiltrated a tumor. That is increasingly becoming a reliable indicator of the likelihood of someone responding to therapy. Anything to say about that?

Alexander M. Lesokhin, MD:

Yeah, it’s this tumor mutational burden. Mismatch repair deficient tumors have a higher tumor mutation burden. It’s the presence of an immune-infiltrated, T-cell-infiltrated so-called “hot tumor,” which seems to be associated with the efficacy of these therapies. And presence of this PD-L1 marker, which is, in a way, a marker of an inflamed tumor.

Brian Brewer:

All right. Ariella, I will let you get the last word. And then we’ll wrap up. Any parting words for the patients and caregivers who are watching today’s webinar?

Ariella Chivil:

Sure. So first of all, just thank you so much, everyone, for listening in. I just want to add that you are your own best advocate. We talk about that a lot. But ultimately, you are an expert in your own life, in your own health. And only you can provide the crucial data and insights into what it’s like to live with this illness and treatment day in, day out. And to provide information to your physician is crucial to make sure that you have a positive outcome.

The more transparent and forthright that you can be, the better treatment options you’ll have that are tailored to you. I’m incredibly lucky that I got to work with someone like Dr. Lesokhin and his team who really enabled me to help make these decisions and participate in my own care plan.

And I would encourage you all to do so and to explore these options as they come up, to educate yourselves, to inform yourselves and arm yourself with that information and be prepared to ask as many questions as you can and to take care of yourself as best you can. And thank you again. And I’m happy to be here in this position today. And I’m happy to be alive to see all these wonderful drug discoveries that have come up and to see the success of all this research. And I’m looking forward to the future to seeing what options we have available for all of us patients and see what future we can make together.

Brian Brewer:

Ariella, is there a way for any of our viewers to contact you? Are you on social media? Is there any handle you care to share?

Ariella Chivil:

Sure. You can find me on Twitter @cruella_chivil. Feel free to just shoot me a note.

Brian Brewer:

That’s wonderful. Well, I want to thank all the viewers for submitting the questions. I hope that you found today’s webinar insightful and that it helps guide you or a loved one in discussing immunotherapy options with an oncologist. Once again, I’d like to thank our generous sponsors for making this webinar series possible and remind you all that you can view this and all of our other past webinars at cancerresearch.org/webinars. Ariella, Dr. Lesokhin, thank you so much for joining us and thank all of you for watching.

Alexander M. Lesokhin, MD:

Thank you. It’s been an honor.

Ariella Chivil:

Thank you.