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PcP Prophylaxis in Relapsed Follicular Lymphoma

Panelists: Ian W. Flinn, MD, PhD, Sarah Cannon Research Institute; Joshua Brody, MD, Icahn School of Medicine at Mount Sanai; Nathan H. Fowler, MD, University of Texas MD Anderson Cancer Center; John P. Leonard, MD, New York Presbyterian/Weill Cornell Medical Center; Matthew Lunning, DO, University of Nebraska Medical Center; Sonali M. Smith, MD, University of Chicago
Published: Wednesday, Aug 22, 2018



Transcript: 

Ian W. Flinn, MD, PhD: Josh, this class of drugs, because infections are common in refractory patients with lymphoma, but also in patients receiving these therapies, do you do anything for prophylaxis?

Joshua Brody, MD: In the beginning, we did little or nothing for idelalisib prophylaxis. There was a standard-of-care change for both CMV (cytomegalovirus), PCR monitoring. We should emphasize the CMV PCR monitoring, because we saw some people were doing serology monitoring, which I don’t think can be very helpful. PCP prophylaxis was built in to the duvelisib studies pretty early on. In my common practice now, we have a little bit of both. We have some patients with histories of opportunistic infection, different types, and they end up with PCP prophylaxis. I have some patients who have already been on idelalisib for 4 years and never had any problem, and I’ve not switched them over. There were these infection concerns with some of the randomized idelalisib studies, but it wasn’t that people were getting sick from PCP; it was mostly a random assortment of other things, even standard community-acquired pneumonias that are infections. It wasn’t really clear to us, that just PCP prophylaxis in these patients, would make the difference in that risk for infection.

I don’t actually have an absolute standard of care, and I have to say the CMV PCR monitoring in our hands has not been very helpful. We have not caught a conversion that we then treated. I would say still, the majority of our idelalisib patients are the ones [who] have been on for a while, and most of them have not switched over to PCP prophylaxis. Duvelisib may be different guidelines, and then copanlisib, I don’t think we have any strong guidelines to push for PCP prophylaxis.

Ian W. Flinn, MD, PhD: The duvelisib experience was based on the idelalisib experience, and it was based on the phase I study with idelalisib where very early on there was an agreement for the investigators to put people on PCP prophylaxis. All these studies are a little bit of a mixed bag, because in my chronic lymphocytic leukemia patients—I don’t care what I’m treating with, relapsed/refractory—I put everyone on PCP prophylaxis. I think it’s a reasonable point that we don’t know. It is a fairly inexpensive therapy, barring someone getting a rash, with mostly [an] upside to add PCP prophylaxis. Any other differences that people can see between these 3 agents? Of course, they hit the different isoforms. But from a clinical use standpoint, Nathan, any one patient population that you might treat differently, might select one therapy versus the other?

Nathan H. Fowler, MD: Yes. Well, let me back up a little bit. When we look at the side effect profile, as you mentioned earlier, it’s not clear. We really don’t understand why patients are having different toxicity profiles. If you look at the amount of delta and gamma that’s hit across these different isoforms, they are variable. Could it be the dosing? My main point of that is that even if you pick a patient population, you should be monitoring these patients very carefully regardless of the drug that you pick. But if I had a patient, for example, that I’m a little more worried about compliance, I might be using something that is intravenous, even the copanlisib intravenous. Then you’re giving that in the clinic. Patients that tend to have a history of uncontrolled diabetes, I might be picking something like idelalisib first. But outside of that, again, they’re fairly similar. If you look at the response rates and look at the remission times in both drugs, they’re almost identical; both of them are going to control. The median progression-free survival of both these drugs is about a year. Overall response rates are in the 50%, 60% response rate range. So, one’s oral, one’s intravenous, a little bit different toxicity profiles. You just have to individualize it to the patient.

Sonali M. Smith, MD: I was just going to say that I think the driving force, at least in my practice, has been the copays and the insurance aspect. Because even though there is support to getting some of the oral agents, it runs out after a period of time. So, the first year is great and then they run out. These are currently, unfortunately, treatment until progression, so that’s a real barrier.

Joshua Brody, MD: I just realized copanlisib kind of sounds like copay, because we’re going to get that covered. I don’t know if that was built in to the naming system.

Matthew Lunning, DO: I, too, was concerned about the diabetes part of copanlisib. But then at this ASCO, there’s actually an abstract where they pulled out their diabetic patients on trial. It actually made me a little more reassured that you could do it in a type 2 diabetic through their clinical trials.

Joshua Brody, MD: But, I think they had some A1C limitations, so people with very badly controlled diabetes.

Matthew Lunning, DO: Right. You had to have a certain blood sugar to get started and things like that. You had to follow the protocol, but at least it shows that that population could still be treated.

Joshua Brody, MD: The concerns with those patients is, it’s going to be oncologists who are just starting to use that medicine, overreacting, and treating patients with insulin; calling up their endocrinologist; and the insulin is going to last longer in the copanlisib. They’re going to get hypoglycemia afterwards.

Matthew Lunning, DO: That’s where the danger lives.

Sonali M. Smith, MD: That’s exactly right.

Joshua Brody, MD: Really, the majority of patients are all back exactly at baseline after 24 hours, no matter how they got treated with fluids or occasionally insulin. Mostly we should be treating those people less, in terms of covering those high sugars.

Sonali M. Smith, MD: Right. I think that actually a really good point for safety is not to give the insulin, not to react to that hyperglycemia, because you will overshoot. You wonder if with R-CHOP, we don’t check sugar levels, but I’ll bet they’re all hyperglycemic, too.

Ian W. Flinn, MD, PhD: Yes, they certainly could be.

Transcript Edited for Clarity 

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Transcript: 

Ian W. Flinn, MD, PhD: Josh, this class of drugs, because infections are common in refractory patients with lymphoma, but also in patients receiving these therapies, do you do anything for prophylaxis?

Joshua Brody, MD: In the beginning, we did little or nothing for idelalisib prophylaxis. There was a standard-of-care change for both CMV (cytomegalovirus), PCR monitoring. We should emphasize the CMV PCR monitoring, because we saw some people were doing serology monitoring, which I don’t think can be very helpful. PCP prophylaxis was built in to the duvelisib studies pretty early on. In my common practice now, we have a little bit of both. We have some patients with histories of opportunistic infection, different types, and they end up with PCP prophylaxis. I have some patients who have already been on idelalisib for 4 years and never had any problem, and I’ve not switched them over. There were these infection concerns with some of the randomized idelalisib studies, but it wasn’t that people were getting sick from PCP; it was mostly a random assortment of other things, even standard community-acquired pneumonias that are infections. It wasn’t really clear to us, that just PCP prophylaxis in these patients, would make the difference in that risk for infection.

I don’t actually have an absolute standard of care, and I have to say the CMV PCR monitoring in our hands has not been very helpful. We have not caught a conversion that we then treated. I would say still, the majority of our idelalisib patients are the ones [who] have been on for a while, and most of them have not switched over to PCP prophylaxis. Duvelisib may be different guidelines, and then copanlisib, I don’t think we have any strong guidelines to push for PCP prophylaxis.

Ian W. Flinn, MD, PhD: The duvelisib experience was based on the idelalisib experience, and it was based on the phase I study with idelalisib where very early on there was an agreement for the investigators to put people on PCP prophylaxis. All these studies are a little bit of a mixed bag, because in my chronic lymphocytic leukemia patients—I don’t care what I’m treating with, relapsed/refractory—I put everyone on PCP prophylaxis. I think it’s a reasonable point that we don’t know. It is a fairly inexpensive therapy, barring someone getting a rash, with mostly [an] upside to add PCP prophylaxis. Any other differences that people can see between these 3 agents? Of course, they hit the different isoforms. But from a clinical use standpoint, Nathan, any one patient population that you might treat differently, might select one therapy versus the other?

Nathan H. Fowler, MD: Yes. Well, let me back up a little bit. When we look at the side effect profile, as you mentioned earlier, it’s not clear. We really don’t understand why patients are having different toxicity profiles. If you look at the amount of delta and gamma that’s hit across these different isoforms, they are variable. Could it be the dosing? My main point of that is that even if you pick a patient population, you should be monitoring these patients very carefully regardless of the drug that you pick. But if I had a patient, for example, that I’m a little more worried about compliance, I might be using something that is intravenous, even the copanlisib intravenous. Then you’re giving that in the clinic. Patients that tend to have a history of uncontrolled diabetes, I might be picking something like idelalisib first. But outside of that, again, they’re fairly similar. If you look at the response rates and look at the remission times in both drugs, they’re almost identical; both of them are going to control. The median progression-free survival of both these drugs is about a year. Overall response rates are in the 50%, 60% response rate range. So, one’s oral, one’s intravenous, a little bit different toxicity profiles. You just have to individualize it to the patient.

Sonali M. Smith, MD: I was just going to say that I think the driving force, at least in my practice, has been the copays and the insurance aspect. Because even though there is support to getting some of the oral agents, it runs out after a period of time. So, the first year is great and then they run out. These are currently, unfortunately, treatment until progression, so that’s a real barrier.

Joshua Brody, MD: I just realized copanlisib kind of sounds like copay, because we’re going to get that covered. I don’t know if that was built in to the naming system.

Matthew Lunning, DO: I, too, was concerned about the diabetes part of copanlisib. But then at this ASCO, there’s actually an abstract where they pulled out their diabetic patients on trial. It actually made me a little more reassured that you could do it in a type 2 diabetic through their clinical trials.

Joshua Brody, MD: But, I think they had some A1C limitations, so people with very badly controlled diabetes.

Matthew Lunning, DO: Right. You had to have a certain blood sugar to get started and things like that. You had to follow the protocol, but at least it shows that that population could still be treated.

Joshua Brody, MD: The concerns with those patients is, it’s going to be oncologists who are just starting to use that medicine, overreacting, and treating patients with insulin; calling up their endocrinologist; and the insulin is going to last longer in the copanlisib. They’re going to get hypoglycemia afterwards.

Matthew Lunning, DO: That’s where the danger lives.

Sonali M. Smith, MD: That’s exactly right.

Joshua Brody, MD: Really, the majority of patients are all back exactly at baseline after 24 hours, no matter how they got treated with fluids or occasionally insulin. Mostly we should be treating those people less, in terms of covering those high sugars.

Sonali M. Smith, MD: Right. I think that actually a really good point for safety is not to give the insulin, not to react to that hyperglycemia, because you will overshoot. You wonder if with R-CHOP, we don’t check sugar levels, but I’ll bet they’re all hyperglycemic, too.

Ian W. Flinn, MD, PhD: Yes, they certainly could be.

Transcript Edited for Clarity 
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