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Abscopal Effect and Pseudoprogression in Melanoma

Panelists: Jeffrey Weber, MD, PhD, NYU Langone Medical Center; Reinhard Dummer, MD, University of Zurich Hospital;Axel Hauschild, MD, University of Kiel;Caroline Robert, MD, PhD, Gustave Roussy; Dirk Schadendorf, MD, University Hospital Essen
Published: Wednesday, Jan 04, 2017


Transcript:

Jeffrey Weber, MD, PhD:
Let’s go to urban legend number 4 and think about it just for a minute. Radiotherapy plus immunotherapy in the abscopal effect. Do we think the abscopal effect is real, or is it an urban legend? So let’s go around the room. Here you have four of the world’s experts in melanoma. Do you think the abscopal effect is real? Have you seen it? Meaning, giving radiotherapy after progression on immunotherapy and seeing a subsequent systemic response either in the presence or absence of further immunotherapy? That’s, to me, what the abscopal effect is.

Reinhard Dummer, MD: I’ll make it short, and I have to say, I have never seen a real case where I think this is what is reported.

Jeffrey Weber, MD, PhD: Okay. And remember, that’s exactly what was published by Mike Postow in the New England Journal—progression on immunotherapy, then radiation to one place, then a subsequent systemic response. Axel, have you ever seen this?

Axel Hauschild, MD: I have seen multiple cases.

Jeffrey Weber, MD, PhD: Really?

Axel Hauschild, MD: Yes.

Caroline Robert, MD, PhD: I have seen some cases.

Jeffrey Weber, MD, PhD: When you say ‘some cases’, what numbers are we talking about?

Caroline Robert, MD, PhD: Maybe a handful.

Jeffrey Weber, MD, PhD: A handful?

Caroline Robert, MD, PhD: Yes.

Dirk Schadendorf, MD: For me, never.

Jeffrey Weber, MD, PhD: I have probably seen it once.

Axel Hauschild, MD: I think that you defined abscopal effect very widely. For me, the true abscopal effect is if you irradiate a lesion. Other lesions that were not irradiated, the non-irradiated ones, fade away, and not in the presence of another immunotherapy. And, I think, this is something that is really interesting. It could be a late benefit from the previous so-called progressive disease on PD-1 antibodies. Or it was a pseudoprogression that turns to an objective response later on. So, the abscopal effect, to define correctly for me, it’s a black box.

Caroline Robert, MD, PhD: Yes. Well, it’s difficult because sometimes you have a patient who responds, but you have the therapy underneath, so you don’t know. Even the responses are rare with ipilimumab– you cannot rule out that it’s ipilimumab…

Axel Hauschild, MD: That’s what I meant.

Caroline Robert, MD, PhD: But, you have to be in the situation that you described, Jeff, that patients really progress, and we are sure. Then we irradiate and they begin to respond, so that indeed is rare.

Jeffrey Weber, MD, PhD: Although, pseudoprogression is a real phenomenon. I think we all agree, we’ve all seen pseudoprogression. But, Dirk, what do you tell the patients? How often are you going to see this pseudoprogression?

Dirk Schadendorf, MD: So, I think in the era of ipilimumab, we have talked a lot about pseudoprogression. I think we will see pseudoprogressions in the realm of maybe 10%, possibly even less, of patients who have true pseudoprogression, which then really turns into a real response. There might be some lesions where there is flare-up by inflammation, which you also see with initial increase on the scanning, and then also a decrease. But, overall, that pseudoprogression—during the entire scanning is turning into a partial or complete response—is a rare thing. Whether this is an issue with PD-1 antibodies in comparison to ipilimumab, it’s not so clear. I think we have a learning curve in that. I think, also, the way we are scanning and the scanning intervals, also, determine when we call this pseudoprogression. If we do scanning only every 12 weeks, the likelihood that we would see patients who have pseudoprogression would probably decrease. In contrast, if we do scanning earlier, after 6 or 8 weeks when the immune system is full in action, it is actually causing problems for the radiologist to discriminate between tumor progression and pseudoprogression.

Transcript Edited for Clarity
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Transcript:

Jeffrey Weber, MD, PhD:
Let’s go to urban legend number 4 and think about it just for a minute. Radiotherapy plus immunotherapy in the abscopal effect. Do we think the abscopal effect is real, or is it an urban legend? So let’s go around the room. Here you have four of the world’s experts in melanoma. Do you think the abscopal effect is real? Have you seen it? Meaning, giving radiotherapy after progression on immunotherapy and seeing a subsequent systemic response either in the presence or absence of further immunotherapy? That’s, to me, what the abscopal effect is.

Reinhard Dummer, MD: I’ll make it short, and I have to say, I have never seen a real case where I think this is what is reported.

Jeffrey Weber, MD, PhD: Okay. And remember, that’s exactly what was published by Mike Postow in the New England Journal—progression on immunotherapy, then radiation to one place, then a subsequent systemic response. Axel, have you ever seen this?

Axel Hauschild, MD: I have seen multiple cases.

Jeffrey Weber, MD, PhD: Really?

Axel Hauschild, MD: Yes.

Caroline Robert, MD, PhD: I have seen some cases.

Jeffrey Weber, MD, PhD: When you say ‘some cases’, what numbers are we talking about?

Caroline Robert, MD, PhD: Maybe a handful.

Jeffrey Weber, MD, PhD: A handful?

Caroline Robert, MD, PhD: Yes.

Dirk Schadendorf, MD: For me, never.

Jeffrey Weber, MD, PhD: I have probably seen it once.

Axel Hauschild, MD: I think that you defined abscopal effect very widely. For me, the true abscopal effect is if you irradiate a lesion. Other lesions that were not irradiated, the non-irradiated ones, fade away, and not in the presence of another immunotherapy. And, I think, this is something that is really interesting. It could be a late benefit from the previous so-called progressive disease on PD-1 antibodies. Or it was a pseudoprogression that turns to an objective response later on. So, the abscopal effect, to define correctly for me, it’s a black box.

Caroline Robert, MD, PhD: Yes. Well, it’s difficult because sometimes you have a patient who responds, but you have the therapy underneath, so you don’t know. Even the responses are rare with ipilimumab– you cannot rule out that it’s ipilimumab…

Axel Hauschild, MD: That’s what I meant.

Caroline Robert, MD, PhD: But, you have to be in the situation that you described, Jeff, that patients really progress, and we are sure. Then we irradiate and they begin to respond, so that indeed is rare.

Jeffrey Weber, MD, PhD: Although, pseudoprogression is a real phenomenon. I think we all agree, we’ve all seen pseudoprogression. But, Dirk, what do you tell the patients? How often are you going to see this pseudoprogression?

Dirk Schadendorf, MD: So, I think in the era of ipilimumab, we have talked a lot about pseudoprogression. I think we will see pseudoprogressions in the realm of maybe 10%, possibly even less, of patients who have true pseudoprogression, which then really turns into a real response. There might be some lesions where there is flare-up by inflammation, which you also see with initial increase on the scanning, and then also a decrease. But, overall, that pseudoprogression—during the entire scanning is turning into a partial or complete response—is a rare thing. Whether this is an issue with PD-1 antibodies in comparison to ipilimumab, it’s not so clear. I think we have a learning curve in that. I think, also, the way we are scanning and the scanning intervals, also, determine when we call this pseudoprogression. If we do scanning only every 12 weeks, the likelihood that we would see patients who have pseudoprogression would probably decrease. In contrast, if we do scanning earlier, after 6 or 8 weeks when the immune system is full in action, it is actually causing problems for the radiologist to discriminate between tumor progression and pseudoprogression.

Transcript Edited for Clarity
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TitleExpiration DateCME Credits
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