Oncology Pharmacovigilance Clinic

Podcast Transcript

Dale Shepard, MD, PhD: Cancer Advances, a Cleveland Clinic podcast for medical professionals, exploring the latest innovative research and clinical advances in the field of oncology.

Thank you for joining us for another episode of Cancer Advances. I'm your host, Dr. Dale. Shepard, a medical oncologist here at Cleveland Clinic directing the Taussig Early Cancer Therapeutics Program and Co-Director for the Cleveland Clinic Sarcoma Program. Today I'm very happy to be joined by Dr. Wen Ma, Director of the Novel Cancer Therapeutics Center, and Dr. Lucy Boyce Kennedy, Director of the Pharmacovigilance Clinic. Dr. Kennedy was previously a guest on this podcast to discuss improving outcomes for patients with metastatic melanoma and Dr. Ma was previously here to discuss the Novel Therapeutics Clinic. Both episodes are still available for you to listen to. Today we're here to talk about the Oncology Pharmacovigilance Clinic. So maybe just start out, just remind us a little bit about what you do here at the clinic. Dr. Kennedy, let's start with you.

Lucy Boyce Kennedy, MD: Sure. Thank you for having me back. I'm a cutaneous oncologist here at Cleveland Clinic. I see patients with melanoma and other skin cancers, and I also direct the Pharmacovigilance Clinic and I see patients in that clinic as well.

Dale Shepard, MD, PhD: Excellent. Dr. Ma?

Wen Wee Ma, MBBS: Dale, thank you so much for having me back. I didn't believe that you're going to invite me back again.

Dale Shepard, MD, PhD: Welcome back.

Wen Wee Ma, MBBS: So yes. So I'm a medical oncologist focusing in GI cancers and also early-phase drug development as well.

Dale Shepard, MD, PhD: Excellent. So today we're going to talk about this Oncology Pharmacovigilance Clinic and we're going to get into the details about that. And people can kind of go back and listen. But let's kind of just put this in perspective. This is part of this Novel Therapeutics center. So maybe, Wen, you could just give us a really brief overview about what this whole center is and how pharmacovigilance and we'll get into more detail about fits in.

Wen Wee Ma, MBBS: Sure, sure. So one of the role that we are trying to do that I'm overseeing is how do we push us forward in moving novel ideas, novel treatments for cancer. Obviously there is going to be new side effects that come together with that. So as part of the center, we are very aware of side effects that patients can get. And one of the area that is receiving a lot of interest and that is really dramatically improving patient's life is using immunotherapy. So together with that, we have patients that continue to do very well. I think metastatic melanoma, one of the disease type Lucy treat, has really fantastic outcome, but unfortunately they do have side effect from the immunotherapy.

Dale Shepard, MD, PhD: So just give us an idea when we talk about these immune related adverse events, what kind of side effects are we talking about?

Lucy Boyce Kennedy, MD: This is always a hard question to answer in clinic because I tell patients you can see any side effect at any time. But I explain to patients’ immune therapies are like taking a break, like a CAR break off the immune system. But you can also get the immune system attacking your normal organs in your body and it can attack any of the organs in your body. So we can really see this inflammatory spectrum of side effects that can affect any organ system. Some are more common than others. And there's acute side effects, and then there can also be long-term toxicity. So some of our melanoma patients will do really well in the long-term from a cancer standpoint, but may have IREs that can be really long-lasting and that can have an important effect on quality of life.

Dale Shepard, MD, PhD: And for perspective, what percentage of patients end up developing significant immune-related adverse events?

Lucy Boyce Kennedy, MD: It depends on the medication regimen. Many patients in oncology will get a PD-1 or PDL-1 antibody, and for those patients I quote them about a 10% risk of getting a grade three or four toxicity.

Dale Shepard, MD, PhD: And does this typically just decrease quality of life? Does it lead to discontinuation of therapies? A little bit of both?

Lucy Boyce Kennedy, MD: It can do any of those things and it depends on the toxicity. So some examples would be hepatitis that may be picked up on labs. Many of the toxicities, or most of them, are reversible often with steroids. There's other toxicities like arthralgia. So some patients with underlying arthritis will develop worsening arthalgias and that can be long-lasting even after stopping the medication. So there's a question of what treatment we should use for it, acute lab abnormalities or other symptoms, but then also how can we support patients in their survivorship toxicities and ongoing symptoms.

Dale Shepard, MD, PhD: And so, Wen, tell us a little bit about certainly this as immunotherapies become more common standard therapies, sort of that drug development angle. How does having a clinic like this sort of dovetail into some of the newer therapies and how we manage those?

Wen Wee Ma, MBBS: Sure, sure, sure. So to kind of historically, as you know Dale and Lucy, we've been always thinking about using immune system effect against cancer and that has not been really the case until maybe five, six years ago with different immune checkpoint inhibitor treatment. So fast forward to now, immune checkpoint inhibitor treatment is standout care and on the horizon there is even more different type of treatment that is coming online that is really augmenting the immune system to treat the cancer. So for example, CAR T cells, or the way that we can take the patient's cancer cell out, modify it and then re-infuse the modified immune cells back into the patient and then causing an immune reaction to the cancer. So those processes can cause what we call immune-related toxicity. So that really come in play.

So given what we have learned here about the management of immune-related toxicity, it's very important for us to learn how to take care of it, to learn about what the body is doing because those exciting treatment is coming down the pipeline and we need to really know how to manage it so that in the future we can continue to innovate.

Dale Shepard, MD, PhD: So one of the first things we did here at the Cleveland clinic was establish a tumor board. As we start working toward eventually this clinic, tell us a little bit about the tumor board concept to manage these.

Lucy Boyce Kennedy, MD: Yeah, so I think it all comes back to this question that Dr. Fontaine and the melanoma program had asked previously of how can we best manage these patients toxicities and how can we support them through and after their treatment? So the IRE Tumor Board was founded in 2017 and it was put together of a group of different subspecialists across really all different fields with some examples being GI, rheumatology, endocrinology, among many others, specific physicians with interests within their specialty related to IRE management.

And the tumor board met twice a month. It was a virtual and these challenging cases would be presented, so patients where they have steroid refractory IREs, need biologics or other steroids bearing agents. Patients who have really complex situations, for example, patients with a history of autoimmune disease potentially, or a history of transplant where there's a question of what's the best management of these patients in the immune therapy era. And this group will come together to discuss these cases. And that, as you mentioned, sort of been part of the trajectory here that's led to the creation of the Pharmacovigilance Clinic.

Dale Shepard, MD, PhD: And then when we think about setting up this clinic, what sort of services are provided by the clinic? What does the clinic look like?

Lucy Boyce Kennedy, MD: Yeah. So the Pharmacovigilance Clinic is a multi-specialty clinic. It's held in the melanoma pod in Taussig, so the providers are in the same place. It's myself from medical oncology and then we have different providers from different specialties. So right now we have Dr. Calabrese with rheumatology, Dr. Zhou with endocrinology, Dr. Smith and Dr. Abdo with pulmonology and then Dr. Jenna recently joined us with hepatology.

So all of us see patients on Friday afternoons in Taussig in the same place. The really nice thing for us, and I think also for our patients, is that all of the providers are located in the same team room. So for me it's been really great experience just being able to look at my colleague across the room and say, "Hey, what do you think about the CT scan? Hey, I'm seeing this patient today and they're not doing well. Could we make a coordinated visit together? Can you follow up with them in a week on steroids?"

So it's a really nice way for our patients to get coordinated care. It's a good referral center for patients from the community who have really complex AEs where maybe steroids or something else has been tried and hasn't worked. It's a good place to come and get a coordinated second opinion.

Dale Shepard, MD, PhD: So historically, these multidisciplinary clinics, they're tough, getting all the right people in the right place, right time. What was the key to success?

Wen Wee Ma, MBBS: Yeah. Dale, as you know, and maybe the audience know, I joined Cleveland Clinic last year. And when I arrived here I found that I was blown away by what's happening here because there's already a group of specialists from different sub-specialties like what Lucy said, oncology, rheumatology, endocrinology, hepatology, who has already been working on this problem. So I'm really blown away by the teamwork there is. So I think what us at Cleveland Clinic does very well is to do teamwork.

So I think when patient come here, that's exactly what they will get. And I would say the key to really having that teamwork is because all of us here, different sub-specialists, we're here to really serve the patient, to take care of the patient. I think that is really the key to really providing good care. And then we aim to really take care of those patients and help the local provider continue the management.

Dale Shepard, MD, PhD: Right now this is an outpatient clinic, is there any consideration of maybe a consultive service to help out with patients who get admitted with these sorts of immune reactions?

Wen Wee Ma, MBBS: So there's two ways to look at that. So there is those acute toxicity where patients can develop almost catastrophic side effects such as Addisonian crisis where there's adrenal insufficiency. Some patients may develop encephalitis. So those patients end up in the hospital really quickly.

The existing setup where we have expert neurologists, for example, expert endocrinologists, so the current system do take care of that very well. But what's really a gap is actually helping to take care of subacute patients or some patients with chronic problem, ongoing IRE, that really need continual care and referring oncologists or provider would need help. I think that's where currently this Pharmacovigilance Clinic is aiming towards. But you're exactly right. As that need arises and as we have more patients who need such care, I think Lucy and the team is going to continue to develop that service.

Dale Shepard, MD, PhD: And so I guess the question with any of these clinics become, and you talked about people being referred in, as these drugs, these immunotherapies become more common, people get some familiarity with managing symptoms, but clearly there are patients that need help. And so who's the right patient? There's a lot of patients on these therapies and they have varying levels of toxicity. Who do you think is the right patient to be referred in?

Lucy Boyce Kennedy, MD: Great questions. I think the patients who I envision being referred to Pharmacovigilance Clinic are patients where they have a complex toxicity where maybe they've tried steroids or they've tried something else already and it hasn't worked. They're still having difficulty with the side effect or the side effect is interfering with their ability to restart their immune therapy.

Other situations will be patients who have other medical problems that may have a really complex interplay with their immune therapy. So patients who have underlying autoimmune disease. There's a risk that can flare with checkpoint inhibitors. So somebody that's had difficulty with that, that may benefit from multi-specialty management. Those are a few examples. I would say as a summary, I think different providers have different levels of experience with different drugs. As we get more and more novel therapies, I think it's really important to bear in mind this is an important resource. If there's a drug a particular provider isn't comfortable with or a side effect they haven't seen before, we're certainly happy to see the patient to help facilitate workup and management of their side effects.

Dale Shepard, MD, PhD: In general, has this clinic primarily been something where people come in, so where you talked about acute and subacute, sort of get all the necessary players involved and then follow up with each of those disciplines, or do they continue to come back to the Pharmacovigilance Clinic for their continued care?

Wen Wee Ma, MBBS: That's a very good point. So this particular clinic, we aim it to be a consultative clinic where referring providers have really difficult situation that they need to manage. And that's when I think this clinic helps a lot where our team of self-specialists can help to evaluate and provide a treatment plan in a consultative role. And obviously in situation where the referring provider would prefer to continue to engage the sub-specialists within the clinic to continue to manage the patient, I think that's available too. So we can work out different model of collaboration together with a referring physician.

Dale Shepard, MD, PhD: But that's an important thing to consider because that way if someone may be somewhat comfortable with managing their patient and they want to refer someone in, they can get a game plan and then kind of play that out themselves.

Wen Wee Ma, MBBS: Right. So the other thing is that sometimes there's some urgency to trying to get the patient to the right sub-specialists. So for example, patient may develop a rare neurological complication that in the outside general practice might have difficulty in accessing through. So this will be a perfect clinic for the patient to be evaluated and quickly triaged and manage appropriately.

Dale Shepard, MD, PhD: When you think about you've got an impressive select collection of specialists already, who would you like to add next if anyone?

Lucy Boyce Kennedy, MD: I think I feel like I undersold the number of people we have because I listed the people we have in person, but we have others who are involved in their own separate buildings. So other people I'll highlight, Dr. Kabbur in dermatology has been really great in leading to quick access for some of our patients. Dr. Kunchok in neurology. Dr. Moudgil in cardiology. I think I almost can name someone in every specialty that I've interacted with. I'd love to see more of them in person. I think it becomes an issue of space in the clinic and often we are able to coordinate same-day appointments, say like one appointment in Taussig and one appointment in Crile with a different subspecialist.

Wen Wee Ma, MBBS: Yeah, I think Cleveland Clinic, our setup, we are actually able to provide all-around care with multiple subspecialists that's not just cancer-oriented. So very different from cancer-focused setting. So we actually have the ability to deliver all-around the care with non-traditional cancer provider.

Dale Shepard, MD, PhD: Which is helpful particularly. I guess the question would be right now this is a physical clinic on our main campus and a lot of our patients are being treated out in regional sites. Is there a thought to try to expand this in some sort of manner to our regional hospitals or regional locations?

Wen Wee Ma, MBBS: Sure, we would love to do that, but like anything, it does take one step at a time. But that would be the dream. But I think the important thing to recognize is that what we want to do is to help the patient but also help the referring provider. So I think the value is really providing that expertise at the right time and the right place. So if that involve expanding out to the region, so be it. But I think the important thing is that it can exist physically or it can exist virtually. And I think what we want to really put forward is that this clinic is available either in person or virtually.

Lucy Boyce Kennedy, MD: And I think a lot of our subspecialists, depending on the specialty, see actually a fair percentage of their patients virtually, particularly endocrinology. So many of our patients do live far away, try to avoid travel to mean campus understandably. We're often able to see patients virtually.

Dale Shepard, MD, PhD: As you grow in terms of the number of drugs involved, the number of diseases and you expand, are there plans for research related to how to best manage these patients?

Lucy Boyce Kennedy, MD: Yeah, absolutely. I think there are a bunch of areas of unmet need that I am hopeful that by collaborating with subspecialists really across the disciplines that we can help move the field forward even faster. I think just some examples of areas where we have need, there are many of them, but some examples would be biomarkers. So how do we predict who are the patients who are going to develop IREs and how do we use that to help counsel patients on an individual level of what to expect with immune therapy? Right now it's really unpredictable. And how do we best manage? So for steroid, refractory IREs or others, when should we start steroids bearing agents? Could we potentially do clinical trials to learn how to best manage IREs? There's really limited data in this space, and I think by putting all of our different multi-specialty perspectives together, we can hopefully help move that forward.

Wen Wee Ma, MBBS: And I think the other area that is traditionally a contraindication for immune checkpoint inhibitor treatment, right? So for example, when they do the clinical trial, the excluded patient who had transplant, right? So I think the team has a different specialist-oriented tours that we have transplanted. For example, oncology nephrologist who is very focused in that. So the question is really how do we take the next step to then help take care of transplant patients who otherwise will be a candidate for immune checkpoint inhibitor treatment? So I think those are areas where when we have a team of experts like what we have here, that we're able to continue innovate, to take care of that group of patients.

Dale Shepard, MD, PhD: Well in a very short period of time you've collected a lot of specialists in tackling a really important area given the prevalence of checkpoint inhibitors and immune therapy. So appreciate you being with us for some insight today.

Wen Wee Ma, MBBS: Thank you.

Lucy Boyce Kennedy, MD: Thank you for having us.

Dale Shepard, MD, PhD: To make a direct online referral to our Cancer Institute, complete our online cancer patient referral form by visiting clevelandclinic.org/cancerpatientreferrals. You will receive confirmation once the appointment is scheduled.

This concludes this episode of Cancer Advances. For more podcast episodes, visit our website, clevelandclinic.org/canceradvancespodcast. Subscribe on Apple Podcasts, Spotify, or wherever you listen to podcasts.

Thank you for listening. Please join us again soon.