Narrator - Dr. Abel 00:00 Welcome to HelixTalk, an educational podcast for healthcare students and providers, covering real life clinical pearls, professional pharmacy topics and drug therapy discussions. This podcast Narrator - ? 00:11 is provided by pharmacists and faculty members at Rosalind Franklin University, College of Pharmacy. Narrator - Dr. Abel 00:17 This podcast contains general information for educational purposes only. This is not professional advice, and should not be used in lieu of obtaining advice from a qualified health care provider. Narrator - ? 00:27 And now on to the show. Dr. Sean Kane 00:31 Welcome to HelixTalk. Episode 111 I'm your co host, Dr. Kane. Speaker 1 00:35 I'm Dr. Patel, and today with us, we have Dr. Tokuchi. She is an oncology pharmacist at the Rush University Hospital System. Dr. Sean Kane 00:45 She's also an assistant professor here at Rosalind Franklin University, and we thought that she would be the perfect person for today's episode, which is entitled The basics of immune checkpoint inhibitors for non oncology healthcare providers. That would be you and I, Dr Speaker 1 01:00 Patel, that sounds good, because I need a refresher. Dr. Sean Kane 01:04 So Dr. tokuchi, welcome to the episode. Speaker 2 01:06 Thank you everyone for having me here today. I'm very excited to talk to you all about the topic at hand. Dr. Sean Kane 01:12 And I will note that today is actually March 17. This episode is going to go live on April 7. So in a way, we're kind of going in a time machine where, right now, you know, the university is locking down. We're in this remote environment now, and we're kind of making the best of it. So when this episode goes live on April 7, hopefully things have calmed down at that point, but there's no way to know, and we're going to kind of work with what we have today. So why don't we get started? And really, we have a case vignette to kind of kick things off. And this is based on a patient that I saw in the ICU. And it turns out that this patient was receiving this drug category called immune checkpoint inhibitors that came out in 2001 I graduated in 2010 so I'd never even heard of this chemotherapy agent, let alone some of the side effects that were absolutely relevant to me as a non oncology provider. And that's really the intent of this episode, is to orient providers, whether they're oncology oriented or not, to what are these immune checkpoint inhibitors and what do you need to know about them? Speaker 1 02:12 And my knowledge, honestly, has been limited to some of those direct drug commercials on TV. So yes, I'm looking Dr. Sean Kane 02:18 forward to it perfect. Well, we'll start with our case vignette. So Jeff is a fictitious patient. He's 64 years old. He has metastatic melanoma, and he comes to the ICU comatose with a blood glucose of 1800 that's not 181,800 that's an absolutely true number. So they do a diagnostic workup for him and diagnose him with HHS, which is hyperosmolar, hyperglycemic state, which is similar to DKA, except you don't have the acidosis component. And the wrinkle here is that Jeff is not a diabetic. He is not overweight. He does not take any medications for diabetes. He has no family history for diabetes, and really, prior to today, there has never been any laboratory evidence or any other symptoms or signs consistent with Jeff having hyperglycemia of any kind, Speaker 1 03:06 and so really, what's going on here? So Dr. Sean Kane 03:09 it turns out that Jeff was receiving a specific chemotherapy regimen that included this drug category called an immune checkpoint inhibitor. And this largely targets something called the PD one, PDL one pathway, and one of the side effects of this drug category are immune related reactions, including new onset type one diabetes. And really we're going to focus on what are these drugs in this episode? What do we need to know about them? And more importantly, what are some of the side effects that these non oncology health care providers may be observing in these patients that are receiving this drug category? Speaker 1 03:41 So to get started with let's just name some of these immune checkpoint inhibitors available. The most common ones that we may interact with or see would be nivolumab (Opdivo) or Opdivo. This was approved in 2014 with another agent called pembrolizumab (Keytruda). And then some of the less popular ones would be atezolizumab (Tecentriq). Speaker 2 04:03 I'll jump in. So atezolizumab, or Tecentriq, is one of the less popular ones. And then there's a few much less frequently used, ICIS, cemiplimab (Libtayo), avelumab (Bavencio), and durvalumab (Imfinzi). Dr. Sean Kane 04:20 Are these less commonly used because they're just newer or is there they just haven't taken the market because of some other reason? Speaker 2 04:28 Yeah, I think it's a combination of both. They're newer agents, and then we're also finding out sort of their place in therapy as we have more clinical trials that are coming out. Dr. Sean Kane 04:38 Now, as I was writing this. Dr. Tokuchi, you sent me an email saying, are we covering some of these other immune checkpoint inhibitors? Can you give us an example of what this other kind of category is that may fall under the umbrella of ICIS? Speaker 2 04:53 Yeah, definitely. One of the agents is actually an anti CTLA four medication, and it's called ipilimumab, or Yervoy. This was actually one of the earlier immunotherapies that was approved back in 2011 and it's technically the first immune checkpoint inhibitor that was originally presented. Dr. Sean Kane 05:13 Now, are we using that on its own? Now? Is it combined? Is it basically not used anymore because we have these newer agents? Yeah. Speaker 2 05:19 So it really depends on the disease state. For example, melanoma, we often combine ipilimumab with one of the other immune checkpoint inhibitors that we mentioned, so like nivolumab, for example. Dr. Sean Kane 05:31 And we're going to kind of restrict today's episode to really these PD one PDL one inhibitors, so we won't really be talking about Yervoy. But just for completeness sake, we should note that that commonly is also under this umbrella of ICIS. Speaker 1 05:43 And so going forward, let's talk about what these ICIS are, what their mechanism of actions are, and how are they really given. So I'm gonna go out on a limb and say, since they're monoclonal antibodies, that they're infusions. Dr. Sean Kane 05:57 Yeah, that's correct. So typically, these are IV infusions given every two, every three, every four weeks are typical, depending on the indication and the drug that you're looking at. These are all humanized IgG monoclonal antibodies. So it makes sense, as you said, that these would be more parenteral, as opposed to like an oral therapy. What I thought was interesting when I was looking into this is that typically, these are not dosed on body weight, body surface area, renal function or hepatic function, you kind of get one dose for that indication in general, and you get what you get, and it's this fixed dose regimen. So Dr. Tokuchi, could you kind of orient the listeners in terms of what these monoclonal antibodies are doing or targeting? Speaker 2 06:34 Yeah, so monoclonal antibodies, or these immune checkpoint inhibitors are very novel, because they have these unique mechanisms of action, unlike our traditional cytotoxic chemotherapies that we think of like cyclophosphamide or anthracyclines. So what these immune checkpoint inhibitors do is that they activate our body's own immune defense to target the different cancers. So for example, our PD one inhibitors and PD one stands for programmed cell death. These are receptors that are found in our body's T cells on the activation of these receptors down regulates, or, in other words, suppresses the immune function normally, specifically through T cell expansion and activation. Now some cancer cells can over express PDL, one which stands for the ligand of that PD one receptor. Now this allows the cancer cells to evade the immune system, so some of our immune checkpoint inhibitors are PD one receptor inhibitors, so they block that ligand from activating the receptor on the surface of the T cell, thus promoting T cell immune activation. Two examples of our PD one inhibitors like you mentioned earlier, are our nivolumab and pembrolizumab. Some of our immune checkpoint inhibitors bind to that ligand so they block that ligand from interacting with a PD one receptor. Dr. Sean Kane 07:55 Now I thought that this was fascinating, the fact that a cancer cell would produce a thing that would go after a T cell and basically make the T cell calm down a little bit, right? The fact that a cancer cell can do that, I thought, was fascinating. And then even cooler is that we've now developed drugs that either block the ligand or the receptor so that this interaction doesn't happen. So then the T cell would potentially recognize that cancer cell as a cancer cell, and then it does whatever it needs to do, from a mechanistic standpoint, to deal with that cancer cell, because normally it would just kind of ignore it and not get activated by the presence of that cancer cell. Speaker 1 08:32 So the cancer spread and mechanism for a lot of different type of cancers are very similar. But where are the checkpoint inhibitors specifically used so like, what kind of cancers are we going to see them used most for Speaker 2 08:46 originally, these medications were utilized to treat more advanced, refractory or relapsed cancers, and this can either be solid tumor malignancies such as melanoma or non small cell lung Cancer that didn't originally respond to our standard of care cancer treatments. So that's our traditional cytotoxic chemotherapies. One of the biggest updates last year that came out of the ASCO Conference, which is the American Society of Clinical Oncology that occurs every year in Chicago, was the role, the expansion role, of these immunotherapies. So originally, like I mentioned, they were utilized in more extensive stages, but data that was presented last year showed that even in the upfront setting. So an example of this is the use of tezolizumab and small cell lung cancer in combination with traditional chemotherapy, can be utilized upfront when we treat these malignancies. Dr. Sean Kane 09:44 Now, I assume that this is not just restricted to solid cancers anymore. Are there any hematologic malignancies that these are also being used for? Absolutely. Speaker 2 09:54 We have some data to show the support of using these agents in hematologic malignancies such as Hodgkin lymphoma. Dr. Sean Kane 10:01 Now, as I was reading more about this, I noted that this drug class the immune checkpoint inhibitors that they are kind of first of its kind in terms of FDA evaluating and approving this drug class as a tissue agnostic immune therapy, meaning that the approval was not based on lung cancer or breast cancer, but it was based on the actual immunohistochemistry of the cancer cells itself. Would you kind of comment on that as well? Speaker 2 10:27 Yeah, of course. So due to their mechanism of action determining that Pdl, one expression by immunohistochemistry or ich, is often done in certain malignancies, and there is an FDA approved diagnostic tests that's often a prerequisite for the treatment of these agents. So whether you know a patient's insurance is going to approve the medication or not, however, determining that PDL one expression doesn't necessarily have to be done in every type of malignancy, so it basically changes depending on what setting you're using the medication, but there is a test available that you can check the expression of that PDL one, and Speaker 1 11:07 then considering the side effect profile that we're going to dive into a little bit later, it seems like it's a smart thing to do to make sure that we're doing this pre screening and making sure that the patients do qualify for this treatment. Let's talk about how effective they are. Speaker 2 11:23 Yeah, so usually, cancers, response or lack of response, typically occurs within six months. So when we think about the differences between the activities of our traditional chemotherapies, those tend to act faster on the tumor, so we see the toxicities much quicker, and then often a response to the therapy much quicker, whereas with these immunotherapies, it takes upwards to six months. So the optimal duration of therapy as of now is not really known. A lot of the duration of therapy can vary depending on the disease state that you're treating and also the setting of when you're treating the disease, so whether it's in the frontline setting versus the maintenance setting. Speaker 1 12:06 And then in my review, I also read that some of the immune therapies kind of start working right after the infusion, versus these can take a little bit longer to start taking the effect, but once they're given the effect stays for a longer period of time. Is that true? Speaker 2 12:23 Dr. tokuchi, correct, yes. Dr. Sean Kane 12:26 So in terms of the typical endpoints that we're looking at. Dr. Tokuchi, could you kind of comment on what is a typical primary endpoint for either cancer trials in general, or in these immune checkpoint inhibitor trials? And kind of what is a typical definition of those endpoints, Speaker 2 12:41 yeah, so we ideally always want our clinical trials to include overall survival. That's sort of the gold standard, but with a lot of these medications, especially in in the phase three trials, we utilize the surrogate endpoints, such as progression free survival. So a lot of the endpoints, or the primary endpoints of the oncology clinical trials will utilize progression free survival and then as secondary outcomes, they may or may not include overall survival. So progression free survival is known as the length of time during and after treatment of the disease in which the patient lives with a disease but does not necessarily Dr. Sean Kane 13:19 get worse. Now that get worse? Does that mean that they don't progress in terms of new tumor sites? Or is there, like, a specific criteria for get worse? Or does it depend on the disease state? Speaker 2 13:30 Yeah, so that will vary on the disease state. So for example, hematologic malignancies are staged and monitored very differently than solid tumors, such as our like non small cell lung cancer, for example, perfect. So in renal cell carcinoma, historically, we've utilized sunitinib, which is a TKI, an oral TKI agent, and that's sort of been the standard of care for years. Again, last year at ASCO data sort of highlighted the role of immunotherapy in renal cell carcinoma, specifically in the first line setting for intermediate to advanced renal cell so the studies looked at nivolumab and ipilimumab combination. So again, that combo in immunotherapy which improved the overall survival by about 32% when compared to the sunitinib arm, which was their standard of care. Also, the trials have looked at pembrolizumab in combination with axitinib, which improved overall survival by about 47% so that's specific for the renal cell carcinoma setting. Dr. Sean Kane 14:34 So you're saying is that overall survival, which is kind of that gold standard endpoint that you mentioned earlier, is improved when we're using these immune checkpoint inhibitors versus what has traditionally been the more standard of care, then correct, yep. What about other disease states? Speaker 2 14:50 So in melanoma, we have utilized these agents in the adjuvant setting or the upfront setting. So currently, nivolumab or pembrolizumab, our category one. Recommendations based on clinically significant improvements in relapse free survival compared to our high dose ipilimumab. Overall survival data hasn't been reported for these trials yet. So this is again in the adjuvant setting and the metastatic setting of melanoma, the problem often becomes resistance or progression through the other lines of therapy. So immunotherapy has really started to be upfront as one of our preferred lines of treatment. So first line options include pembrolizumab or nivolumab or ipilimumab, plus nivolumab, and I believe Speaker 1 15:33 there's some data for the lung cancer, both the small cell and non small cell lung cancer. Can you elaborate on that? Speaker 2 15:39 Dr. tokuji, yeah, so the role of immunotherapy will differ greatly depending on whether we're talking about small cell or non small cell lung cancer. In the non small cell lung cancer setting, one of the biggest updates as far as immunotherapy was the addition of durvalumab, which provided impressive progression free survival and overall survival benefits in a phase three Pacific trial, which investigated the addition of this anti Pdl, one agent to platinum based chemo radiation therapy of note, so this this trial did show that the patients that did receive durvalumab, obviously Did experience more more immune mediated toxicity, which will elaborate a little bit in the next few minutes, in the small cell lung cancer setting the category one recommendation for treatment of extensive disease was based on a phase three trial called the Impower 133 trial, which looked At the addition of atezolizumab in combination with carboplatin and etoposide, and these are traditional chemotherapy agents, the addition of atezolizumab was associated with a higher six month progression free rate and more than a doubling 12 month PFS or progression free survival rate. So statistically significant overall survival as well 12.3 months versus 10.3 months. Speaker 1 17:05 And this is where the ASCO updates on making this as a first line therapy for certain small cell lung cancer kind of comes in play. Correct, correct. Dr. Sean Kane 17:15 Now, a common criticism of newer drugs is going to be the cost, and I'm sure that the oncology world is no stranger to high cost new drug therapies. Where are we at with the financial situation of these agents? Speaker 2 17:29 Yeah, so we always must consider financial toxicity, whether it's in the ambulatory care setting or inpatient care setting. And since I mainly work on the inpatient side of things, I often have to evaluate these medications for inpatient administration, so we must always be cognizant of that financial toxicity. Sometimes you have to have very important and difficult conversations with providers and also patients. Ultimately, I don't think that the finance aspect are going to prevent us from utilizing chemo immunotherapy specifically in the frontline setting due to the overall survival benefit. But it's important to highlight that even though we are seeing these overall survival improvements specifically in the small cell lung cancer setting, for the first time in two decades, I might highlight we need to continue to seek out more cost effective options. Dr. Sean Kane 18:19 So can you give us an idea of cost and how we kind of evaluate that cost. Yeah. Speaker 2 18:24 So most recently, from the HOPA Conference, which occurred a few weeks ago, we had a presentation that showed sort of the impact of the financial toxicity with these immunotherapy agents, so chemotherapy, plus atezolizumab, specifically in the small cell lung cancer setting, increased costs by about $52,000 for a gain of 0.1 quality compared to chemotherapy alone. So if we think about one whole entire quality, that's about half a million dollars. And typically, the threshold for cost effectiveness in the US is about $100,000 Dr. Sean Kane 19:01 per QALY, when you say quality, that's quality adjusted life years, and what you're saying is that about half a million dollars for a quality, quality adjusted life year is quite expensive, given that our threshold is more like 100,000 and we're at 500 plus $1,000 Correct? Yes. So that's the cost, and really what brought this entire drug class to my attention as a non oncology provider is actually the side effect profile of these immune checkpoint inhibitors. And obviously it's going to vary a lot, and it's going to vary based on patient. It's going to vary based on drug that you're using, and things like that. But can kind of group some of these toxicities into three main categories, so infusion related reactions, immune related adverse effects and adverse effects of special interest. So there's kind of three different categories that we're going to go through here. Speaker 1 19:50 So in your inpatient setting, I know you said you kind of evaluating the need for these drugs, but if you were to have patients getting infusions, what kind of infusion related. Added reactions or side effects should we be aware of? Speaker 2 20:04 Yeah, so as you mentioned earlier, Kathy, these are ultimately monoclonal antibodies, so the patients will be at risk for infusion related reactions. Similarly to other monoclonal antibodies, such as rituximab, infusion related reactions are often mild and typically associated with low grade fevers, chills, headaches or nausea, severe reactions have been reported in less than 1% of patients, and they're commonly reported with a value map with any grade reaction occurring in about 25% of patients. The NCCN guidelines recommend that clinicians reference each product's prescribing information in terms of looking to see what pre medications are recommended, because every agent may differ slightly in terms of their recommendation. Mild reactions are generally transient and they don't require therapy interruption or any other interventions. But when we talk about more moderate reactions. We generally manage these patients by holding the infusion or slowing down the rate of infusion, per institutional guidelines, treating with supportive care medications such as antihistamines, acetaminophen, NSAIDS, narcotics or IV fluids. Dr. Sean Kane 21:18 And granted, you know these patients are going to be in a monitored environment, because this is an IV infusion. So it's not like they're injecting at home or something like that. So these are going to be monitored patients. But as pharmacists, we should be aware of these infusion related reactions that can happen, probably with any monoclonal antibody, and this is no exception. Speaker 1 21:36 So jumping on to the immune mediated or immune related adverse events. There's a lot of different organs system can be involved, right? So we're talking about skin, colon, endocrine organ, for example, our patients coming in with type one diabetes out of nowhere, liver, lung tissues, all of this can be implicated. We kind of can dive into a little bit more and talk about, what are the incidence rates and how prevalent these are. Dr. Sean Kane 22:04 And in a way, these side effects are basically the body's immune system attacking a given tissue because we're ramping it up. I mean, as humans, we have immune checkpoints for a reason, so that we don't have the side effects happening as a result of our immune system kind of going off the rails. And now we're giving a drug to really augment that immune system. It's not that surprising then that we see side effects as a result of almost an autoimmune like syndrome that can happen in many of these different tissues in the body, Speaker 1 22:33 dermatologic reactions such as dermatitis or rash, which is the non‑severe rash, but a severe rash like Stevens‑Johnson syndrome or TEN can happen in about 40% of patients. Dr. Sean Kane 22:47 Then the next most common immune related adverse effect is going to be gi oriented. So about 10 to 20% of patients will have colitis or diarrhea, and then most of the other ADRs typically happen much later than that. So the dermatologic and gi side effects occur within the first couple weeks, whereas many of the other ones will happen months later. So one to four months into therapy, we're looking at endocrine side effects, five to 10% incidence rate. This would be either hypo or hyperthyroidism, hypopituitarism, and then, just like our fictitious patient, Jeff, this would also include type one diabetes new onset as a result of this immune mediated reaction. Speaker 2 23:27 Yeah, and I would add that pulmonary immune mediated reactions are also toxicities that are often seen with an incidence of upwards of 10% and pneumonitis is one of the most common ones. So when we talk about pneumonitis, specifically in the cancer patient population, it's very important to rule out an infectious process, especially because steroids are our mainstay of therapy for managing a lot of these immune related toxicities. So if you know you have a patient who has difficulty breathing, you definitely want to rule out any sort of infection with appropriate imaging or even a brochoscopy before you add on steroids to the management. Dr. Sean Kane 24:09 And you know, if you look at the package insert for any of these immune checkpoint inhibitors, you're going to see a laundry list of different tissues and different immune mediated or immune related adverse effects that can happen. This is everything, ranging from adrenal insufficiency to encephalitis. So inflammation of the brain, hepatitis, pituitary gland, of inflammation causing hormonal disturbances, nephritis, uveitis, iritis, in terms of ocular toxicity, myocarditis, so toxicity of the heart tissue itself, really any organ you can list, is going to be described as a potential immune related side effect, although the ones that we mentioned earlier, dermatologic gi endocrine and pulmonary, those are going to be your most common ones. Speaker 1 24:55 Now, what are we about to say is shocking? But, and it sounds like somebody who's going through these immune related adverse events is rough, right? Because they're they're pretty severe, but a presence of immune related adverse event is actually a good prognostic factor in this case, because we know that the drug is actually working even after the drug is stopped. Is that correct? Speaker 2 25:22 Dr. tokuchi, yeah, absolutely. So you want to be able to find that balance between, you know, what your patient is able to tolerate and managing those toxicities, and then also the benefit that the patient is receiving from these medications. So this is where monitoring and managing this toxic the toxicities becomes very important, and educating the patients to be able to recognize those toxicities themselves is also very crucial. Speaker 1 25:50 And I believe some of the major guidelines, like the NCCN or the ASCO or the European Society of medical oncology, kind of do list this management of the side effects pretty detailed. Speaker 2 26:03 Yeah, these guidelines are extremely detailed, so they range between 60 to 120 pages each. So some light reading there for providers. So I do want to highlight that there's three different guidelines that have been published, and it's also highly encouraged that institutions do create their own internal guidelines when for managing these toxicities, because even though the NCCN, ASCO and asmo do have overlapping recommendations, there are some slight differences between these guidelines. So it's very important for institutions to kind of keep their internal guidelines up to date in order to appropriately care for these patients. Dr. Sean Kane 26:41 I think it might be helpful for listeners to just get a sense of like, what would be a typical symptom and management of these different adverse effects. Now, granted, you know, these are 60 to 100 page guidelines, for a reason is that there's a lot of detail and a lot of consideration, so we're absolutely glossing over a lot of really important stuff just to kind of provide some context for a typical provider of what is a typical side effect and how would it be managed. Before we get there, we might as well mention that even if a patient is asymptomatic, there's routine monitoring for all of these immune checkpoint inhibitors that relate to the typical side effects that we see. So checking renal function with BU and serum creatinine, checking hepatic dysfunction with LFTs, liver function tests, checking in a thyroid panel, blood glucose, and then, obviously, any symptoms that the patient is having that may prompt additional tests as well. So monitoring is really important, and as we do that, monitoring, if we start seeing a side effect, we'll use gi toxicity or colitis or diarrhea as an example. Kind of, how do we define that in terms of severity? Because, you know, if patient has diarrhea once, we're probably not going to just stop their therapy. But how do we grade that? And then, what is a typical management so why don't we start with colitis or GI toxicity as an example? How do we grade this? And then what is our management strategy for these patients? Speaker 2 28:00 Yeah, so grade one toxicity, which is more of a mild toxicity, an example of this can be an increase in stools or bowel movements that a patient is experiencing per day. So in these patients, we generally continue therapy, although there are some exceptions. But in the general patient population experiencing mild toxicities, we do continue therapy. So a grade one toxicity would be defined as less than four stools per day versus the patient's baseline. So I will highlight that it's very important to discuss with your patients and find out what their baseline bowel movements are before you proceed with any of these grading systems. Dr. Sean Kane 28:38 And if you just think about that, like if I gave a statin to a patient and said, You're going to have three bowel movements extra per day, that probably would not be a tolerable side effect for a statin. But for something like this, I think the game is a little bit different in terms of why we're treating them. They have, you know, some type of cancer. And even though that sounds pretty severe in the context of chemotherapy, and side effects associated with chemotherapy, three additional bowel movements per day is actually not as bad as some of the other side effects that we can see Speaker 1 29:10 continuing on to like the grade two toxicities, for example. So in these patients, we generally hold immunotherapy until that toxicity resolves to grade one or lower. So this is where we also consider the addition of systemic steroids. And steroids play a big role in immunotherapy toxicity management, or those immune mediated toxicities. So generally, the prednisone dosing ranges between 0.5 to one milligram per kilo per day, and with the increase in toxicity grade, we also may consider increasing the prednisone dose and then moving forward, like grade three and grade four toxicities. You know, we're we're going to probably give prednisone for the management of the toxicity and then hold the chemo. Therapy. But even then, consider options such as, are we going to re challenge the patient? Are we going to use maybe another checkpoint inhibitor instead of the one that they're giving they're getting currently, right now, if applicable? So yeah, this was just one example of how gi specific toxicity can be managed. But to keep in mind, the guidelines are about 120 pages long, and they can focus on any and every of the organ specific toxicities that we alluded before. So why Dr. Sean Kane 30:29 don't we go back to Jeff and talk about kind of Jeff's prognosis and treatment of his new onset type one diabetes. So he came in with HHS, which is a completely separate topic, but assuming we manage at HHS, just like any other type one diabetic, what are we going to do for Jeff? Well, I'm going to Speaker 1 30:47 imagine that we're going to have to control his blood sugar first. So some sort of insulin drip, endocrine consult would be necessary, making sure we stabilize his blood sugar first. Dr. Sean Kane 30:58 And we just talked about steroids. How we would use that in a colitis type scenario. Do steroids have a role in this particular scenario? Speaker 2 31:06 So unlikely for this toxicity, does Jeff is experiencing the corticosteroids are not helpful because the damage has already been done. So at this point, he permanently has type one diabetes. Dr. Sean Kane 31:18 And really, you know, once he's euglycemic and stable, he potentially could be resumed back on his immune checkpoint inhibitor, even though he had what would be deemed a grade four side effect of the drug. The reason that he could potentially be resumed, even though it typically wouldn't resume for a grade four side effect, is that the damage has been done. We have drugs that can basically supplement the insulin that his body is no longer making and the side effect is one and done. It's a permanent, unfortunately permanent, side effects that we can now manage and even continue the immune checkpoint inhibitor for Jeff, with proper monitoring for other side effects as well. But this is a great example of why we have 120 page documents, is that the management of this particular side effect is so different than the management of a colitis as an example. So Dr. Tokuchi, we've covered a lot of different very important concepts today regarding immune checkpoint inhibitors, for students that are about to take NAPLEX, or practitioners who are kind of just getting to know these this new drug class, what are some of the most pivotal things to know from today's episode regarding immune checkpoint inhibitors, Speaker 2 32:24 I want to mention that our immune checkpoint inhibitors are here, and they're here to stay. So I think students, whether they're in pharmacy school right now, they're they're going to be seeing these agents more and more, whether it's during therapy lectures or when they're out practicing in the inpatient setting, ambulatory care setting in the emergency department. So these agents are here to stay, and it's very important for students and healthcare providers to know that there are specific guidelines available to providers to utilize when managing the toxicities of patients on immune checkpoint inhibitors. So knowing where to find those guidelines is very important. So I will say that the NCCN guidelines are free to any provider if you sign up with your email and they're very accessible. Third point that I want to highlight is that immune mediated toxicities are very unique to this class of medications utilized in oncology. So when we think about the big difference in toxicities between our traditional chemotherapies versus immune mediated therapies, our immune related toxicities are very unique, and as we mentioned previously, they can affect many different areas in a patient's body, so making sure that you're appropriately counseling your patients on signs and symptoms of some of the most common types of toxicities, so those dermatologic toxicities and colitis or diarrhea, so that the patient is becomes his or her own advocate, And if they do recognize those toxicities at home, they can pick up the phone and call their provider. The quicker we identify these toxicities, the easier the management and the better outcome the patient is going to have. And then, last but not least, I would say, steroids, steroids, steroids. Steroids can be utilized in a lot of different settings. It's also very important to consider cases such as our patient, Jeff that we talked about today, where steroids may not be the best option, but again, going back to those guidelines and pulling it up, looking each toxicity up, and seeing what the appropriate management depending on the grade that the patient is experiencing. Dr. Sean Kane 34:39 Well, Dr. tolkucci, I really want to say thank you for your expertise on today's episode for the listeners, if you want to get some show notes and links to references to learn more about these immune checkpoint inhibitors, especially for the non oncology oriented health care provider, you can do so at HelixTalk.com episode 111 we're also on Twitter at helix. Talk, and we love the five star reviews in iTunes to keep us motivated and help us climb those iTunes rankings as well. So with that, I'm Dr. Kane, I'm Unknown Speaker 35:09 Dr. Patel, and I'm Dr. tokucci, and Speaker 1 35:12 with that, said, Thank you so much for being with us today, Dr. tokucci, good luck tomorrow, and stay safe. Narrator - Dr. Abel 35:18 If you enjoyed the show, please help us climb the iTunes rankings for medical podcasts by giving us a five star review in the iTunes Store. Search for HelixTalk and place your review there to Narrator - ? 35:29 suggest an episode or contact us. We're online at HelixTalk.com thank you for listening to this episode of HelixTalk. This is an educational production copyright Rosalind Franklin University of Medicine and Science.