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Optimizing the Use of Ipilimumab/Nivolumab in mRCC

Insights From: Brian Rini,MD, Cleveland Clinic Main Campus; David F. McDermott, MD, Harvard Cancer Center
Published: Sunday, Dec 02, 2018



Transcript: 

Brian Rini, MD: Ipilimumab/nivolumab is frontline therapy. We’ve used a lot of it since April, over the last 6 months. I have probably personally treated 30 or 40 patients with it. Our experience is that most patients do well. The toxicity is manageable. We certainly had anecdotal patients who got really sick and had to go to the hospital, use IV [intravenous] steroids, etcetera. Our system is pretty in-tune with these toxicities now in terms of early intervention and management, and hospitalizations. I think we’re in-tune with that, but even so, some patients can get really sick. Efficacy-wise, it’s hard to say, but we certainly see responses, especially in patients who are very sick. Patients with the worst disease almost respond the best.

David F. McDermott, MD: The toxicity for nivolumab has been well described, these immune-related adverse events, which can pretty much be an “itis” in any organ or inflammation caused by the activation of the immune system, which can affect the normal tissues in any part of the body. Most of them are mild to moderate and well managed. But when you add ipilimumab to nivolumab, you don’t change the profile, so the list of adverse effects is the same. The patients are just more likely to get them and they’re more likely to be intense. You really have to be ahead of the game as far as detecting early adverse effects.

The key, to me, as far as managing a patient on immune checkpoint blockade is early intervention. The only way you really can intervene early is if the patients tell you what they’re going through. The patients have to tell you if they’re having diarrhea early, a new skin rash, or something like that. If they do, the adverse effects are much more reversible than if they wait at home and don’t call in or assume it’s going to get better with time. You really need to act to reverse the adverse effects. If you do, they are manageable in the vast majority of patients.

Brian Rini, MD: I would say, just like with any cancer drug, that you have to get comfortable using this combination. Ipilimumab/nivolumab was approved in melanoma a couple of years prior, so a lot of community oncologists have used it in that setting. The kidney cancer dosing is different. It’s only 1 of ipilimumab and 3 of nivolumab, so it’s actually an easier dosing than melanoma. I think it’s less toxic. If physicians aren’t comfortable, then I would consider having the patients get their 4 induction doses at an academic center. They can certainly come back for the monthly nivolumab maintenance, which is the easier part, and they’re probably over their major toxicity at that point.

David F. McDermott, MD: Right now, we have clinical criteria for selection. We have the intermediate and poor risk groups that are guiding who should get these treatments. That’s the majority of patients with metastatic disease. Hopefully, we can move further beyond that, because obviously clinical criteria are somewhat rough. Hopefully, we can move to biomarker-based criteria.

Some people would like to potentially use PD-L1 [programmed cell death protein 1] expression as that criteria because the response rates, complete response rates, are higher in that group. But we’re still seeing responders in the PD-L1–low group. I don’t think that’s the perfect marker, but I think there will be a lot of interest going further now that we have this regimen in figuring out who the best patients are to get it. Which patient needs both drugs?

Transcript Edited for Clarity 
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Transcript: 

Brian Rini, MD: Ipilimumab/nivolumab is frontline therapy. We’ve used a lot of it since April, over the last 6 months. I have probably personally treated 30 or 40 patients with it. Our experience is that most patients do well. The toxicity is manageable. We certainly had anecdotal patients who got really sick and had to go to the hospital, use IV [intravenous] steroids, etcetera. Our system is pretty in-tune with these toxicities now in terms of early intervention and management, and hospitalizations. I think we’re in-tune with that, but even so, some patients can get really sick. Efficacy-wise, it’s hard to say, but we certainly see responses, especially in patients who are very sick. Patients with the worst disease almost respond the best.

David F. McDermott, MD: The toxicity for nivolumab has been well described, these immune-related adverse events, which can pretty much be an “itis” in any organ or inflammation caused by the activation of the immune system, which can affect the normal tissues in any part of the body. Most of them are mild to moderate and well managed. But when you add ipilimumab to nivolumab, you don’t change the profile, so the list of adverse effects is the same. The patients are just more likely to get them and they’re more likely to be intense. You really have to be ahead of the game as far as detecting early adverse effects.

The key, to me, as far as managing a patient on immune checkpoint blockade is early intervention. The only way you really can intervene early is if the patients tell you what they’re going through. The patients have to tell you if they’re having diarrhea early, a new skin rash, or something like that. If they do, the adverse effects are much more reversible than if they wait at home and don’t call in or assume it’s going to get better with time. You really need to act to reverse the adverse effects. If you do, they are manageable in the vast majority of patients.

Brian Rini, MD: I would say, just like with any cancer drug, that you have to get comfortable using this combination. Ipilimumab/nivolumab was approved in melanoma a couple of years prior, so a lot of community oncologists have used it in that setting. The kidney cancer dosing is different. It’s only 1 of ipilimumab and 3 of nivolumab, so it’s actually an easier dosing than melanoma. I think it’s less toxic. If physicians aren’t comfortable, then I would consider having the patients get their 4 induction doses at an academic center. They can certainly come back for the monthly nivolumab maintenance, which is the easier part, and they’re probably over their major toxicity at that point.

David F. McDermott, MD: Right now, we have clinical criteria for selection. We have the intermediate and poor risk groups that are guiding who should get these treatments. That’s the majority of patients with metastatic disease. Hopefully, we can move further beyond that, because obviously clinical criteria are somewhat rough. Hopefully, we can move to biomarker-based criteria.

Some people would like to potentially use PD-L1 [programmed cell death protein 1] expression as that criteria because the response rates, complete response rates, are higher in that group. But we’re still seeing responders in the PD-L1–low group. I don’t think that’s the perfect marker, but I think there will be a lot of interest going further now that we have this regimen in figuring out who the best patients are to get it. Which patient needs both drugs?

Transcript Edited for Clarity 
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