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Immunotherapy Toxicity Profile

Panelists: Naiyer A. Rizvi, MD, NewYork-Presbyterian Hospital; Taofeek K. Owonikoko, MD, PhD, Winship Cancer Institute of Emory University; Ticiana Leal, MD, University of Wisconsin-Madison; Jamie E. Chaft, MD, Memorial Sloan Kettering Cancer Center
Published: Thursday, Oct 17, 2019



Transcript: 

Naiyer A. Rizvi, MD: Ticiana, one of the issues with patients with small cell disease is that they tend to have more paraneoplastic syndromes and are biologically different from patients with non–small cell disease. What’s your experience with this in terms of what happens to paraneoplastic syndrome? What is the autoimmune toxicity profile of patients with small cell that you’ve treated?

Ticiana Leal, MD: When we started using a combination of chemotherapy and immunotherapy or immunotherapy as monotherapy, we had the concern that in these patients that had higher rates in general compared with other kinds of cancers. Although it’s still rare to have these paraneoplastic syndromes, we would get worsening toxicities, we would get worsening immune-mediated toxicities. My own clinical experience has been that the paraneoplastic syndromes are not significantly worsened by using immunotherapy. Really, it has been a driver mainly of the disease itself.

When patients present with more debilitating neurological paraneoplastic syndromes, I find that it’s difficult to really have patients recover fully. I frequently have a multidisciplinary team with neurology, and a lot of these patients are receiving IVIG [intravenous immunoglobulin]. Then the immunotherapy question becomes difficult. And I think we have limited data to say what really will benefit that patient, so I tend to back off if they really do require immunosuppression and try to focus on the chemotherapy, and try to reduce the burden of disease, and seeing if there’s clinical benefit with control of the disease and improvement of the paraneoplastic syndrome.

Now, for patients who get paraneoplastic syndromes and receive immunotherapy, whether they have higher risk of immune-mediated toxicities, I guess I don’t know that in my own clinical practice I have enough to say that one way or another. But I’m interested in hearing from others if they do have thoughts about that.

Jamie E. Chaft, MD: I would say my experience is a little biased toward combination therapy. As would otherwise be expected, the autoimmune complications are significantly higher.

Naiyer A. Rizvi, MD: Combination of PD-1 [programmed cell death protein 1] and CTLA4.

Jamie E. Chaft, MD: PD-1/CTLA4. And the patients are sicker in general, so they are less equipped to recover from such complications.

Taofeek K. Owonikoko, MD, PhD: My experience using this agent is that while autoimmune-related toxicity in general tends to be higher, I’ve not seen unique paraneoplastic syndromes that we come to associate with small–cell lung cancer appear at the higher frequency than you otherwise would have expected. Having said that, we also know that paraneoplastic syndromes tend to be common in patients with relatively small burden of disease with limited stage. Perhaps as you now go into the limited-stage setting with this agent, we have to pay more attention to the possibility of seeing more paraneoplastic syndrome in that setting. But I’ve not seen a lot of it in the extensive-stage patient.

There have been a few patients where I’ve seen a bit more of CNS [central nervous system] toxicity than I’ve seen with non–small cell lung cancer patients, and it’s unclear to me whether that is direct treatment-related toxicity or just the way the patient would have behaved. But it’s unique that the 2 of them, the 2 patients I have who came with really severe cerebral dysfunction, both of them got combination CTLA4 and PD-1 or PD-L1 [programmed death-ligand 1] agent.

Naiyer A. Rizvi, MD: Yeah, I’ve seen it both with single-agent PD-1 and combinations. It can be that very subtle neurotoxicity manifests only as a little gait disturbance, a little memory dysfunction. Sometimes it’s hard to tell whether it’s from their PCE [pericardial effusion] or just being sick. But I do get the sense that there’s more neurotoxicity in these patients, so just be cognizant of it.

Transcript Edited for Clarity

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Transcript: 

Naiyer A. Rizvi, MD: Ticiana, one of the issues with patients with small cell disease is that they tend to have more paraneoplastic syndromes and are biologically different from patients with non–small cell disease. What’s your experience with this in terms of what happens to paraneoplastic syndrome? What is the autoimmune toxicity profile of patients with small cell that you’ve treated?

Ticiana Leal, MD: When we started using a combination of chemotherapy and immunotherapy or immunotherapy as monotherapy, we had the concern that in these patients that had higher rates in general compared with other kinds of cancers. Although it’s still rare to have these paraneoplastic syndromes, we would get worsening toxicities, we would get worsening immune-mediated toxicities. My own clinical experience has been that the paraneoplastic syndromes are not significantly worsened by using immunotherapy. Really, it has been a driver mainly of the disease itself.

When patients present with more debilitating neurological paraneoplastic syndromes, I find that it’s difficult to really have patients recover fully. I frequently have a multidisciplinary team with neurology, and a lot of these patients are receiving IVIG [intravenous immunoglobulin]. Then the immunotherapy question becomes difficult. And I think we have limited data to say what really will benefit that patient, so I tend to back off if they really do require immunosuppression and try to focus on the chemotherapy, and try to reduce the burden of disease, and seeing if there’s clinical benefit with control of the disease and improvement of the paraneoplastic syndrome.

Now, for patients who get paraneoplastic syndromes and receive immunotherapy, whether they have higher risk of immune-mediated toxicities, I guess I don’t know that in my own clinical practice I have enough to say that one way or another. But I’m interested in hearing from others if they do have thoughts about that.

Jamie E. Chaft, MD: I would say my experience is a little biased toward combination therapy. As would otherwise be expected, the autoimmune complications are significantly higher.

Naiyer A. Rizvi, MD: Combination of PD-1 [programmed cell death protein 1] and CTLA4.

Jamie E. Chaft, MD: PD-1/CTLA4. And the patients are sicker in general, so they are less equipped to recover from such complications.

Taofeek K. Owonikoko, MD, PhD: My experience using this agent is that while autoimmune-related toxicity in general tends to be higher, I’ve not seen unique paraneoplastic syndromes that we come to associate with small–cell lung cancer appear at the higher frequency than you otherwise would have expected. Having said that, we also know that paraneoplastic syndromes tend to be common in patients with relatively small burden of disease with limited stage. Perhaps as you now go into the limited-stage setting with this agent, we have to pay more attention to the possibility of seeing more paraneoplastic syndrome in that setting. But I’ve not seen a lot of it in the extensive-stage patient.

There have been a few patients where I’ve seen a bit more of CNS [central nervous system] toxicity than I’ve seen with non–small cell lung cancer patients, and it’s unclear to me whether that is direct treatment-related toxicity or just the way the patient would have behaved. But it’s unique that the 2 of them, the 2 patients I have who came with really severe cerebral dysfunction, both of them got combination CTLA4 and PD-1 or PD-L1 [programmed death-ligand 1] agent.

Naiyer A. Rizvi, MD: Yeah, I’ve seen it both with single-agent PD-1 and combinations. It can be that very subtle neurotoxicity manifests only as a little gait disturbance, a little memory dysfunction. Sometimes it’s hard to tell whether it’s from their PCE [pericardial effusion] or just being sick. But I do get the sense that there’s more neurotoxicity in these patients, so just be cognizant of it.

Transcript Edited for Clarity
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