Participants Discuss Rare Dual Immunotherapy AE Experiences in NSCLC

John V. Heymach, MD, PhD (Moderator)

Professor, Department of Cancer Biology

David Bruton, Jr Chair in Cancer Research

Chair, Department of Thoracic/Head and Neck Medical Oncology

Division of Cancer Medicine

The University of Texas MD Anderson Cancer Center

Houston, TX

DISCUSSION QUESTIONS

• What is your approach to maintaining immunotherapy when deciding to discontinue a CTLA-4 inhibitor in non­–small cell lung cancer (NSCLC)?
• Which patient and/or disease factors prompt that decision?
• Do you continue chemotherapy plus an immune checkpoint inhibitor?

JOHN V. HEYMACH, MD, PHD: Does anybody have experiences they want to bring up, or other things they'd note about the toxicity for the dual immune checkpoint blockade [in NSCLC]? It seems different than PD-1 alone.

UMASANKAR RAMADOSS, MD: There is a lot less toxicity than with dual immunotherapy that is used for melanoma. Having said that, there is definitely more toxicity than single-agent pembrolizumab [Keytruda] or chemotherapy plus pembrolizumab. Hepatitis is more manageable, and colitis is more manageable; can I give them 10 to 20 mg of steroids and keep on going? Most patients do better with that.

HEYMACH: When you have somebody who has colitis or hepatitis—once they get over it and you give them steroids and you hold for a bit—are you stopping both drugs? Or are you restarting just the PD-1 and seeing how they do?

RAMADOSS: The PD-1; I permanently stop the ipilimumab [Yervoy].

HEYMACH: How have patients been doing in your experience? Are they able to tolerate just the PD-1?

RAMADOSS: Very well. I was able to get them off of the steroid, too.

HEYMACH: That's been my experience as well. Does anybody else want to give their thoughts?

CHRISTIANE ZOGHBI, MD: I followed a patient with a hepatologist with increased liver function test results and hepatitis [as] immune-related [adverse events (AEs)]. I was able, after completing a steroid, to [restart] ipilimumab/nivolumab [Opdivo]. I recall roughly 50% of patients with...immune toxicity tend to have recurrence, so we followed the patient closely. In fact, she has done well, even with rechallenging both drugs.

HEYMACH: That's interesting. There are data of patients who have immune toxicities who appear to have at least as much if not more benefit from the treatment even if you stop the CTLA-4. [It may be that] once their immune system is revved up, they can continue to get benefit in a lot of cases. Do people have other experiences with the dual checkpoint compared with a single checkpoint inhibitor?

MADHU V. MIDATHADA, MD: I saw bad immune neuropathy for 1 patient where it was disabling, and she couldn't walk.

HEYMACH: Was it like an immune [Guillain-Barré syndrome]? I know a lot of times we can't figure out exactly what it is. Did it get figured out?

MIDATHADA: I didn't call it Guillain-Barré syndrome. She saw our neurology department, and they did all kinds of testing. With immunosuppressive treatment, eventually she got better. She had a really nice response and is still in remission of immunotherapy. We held therapy, but the issue got better. She improved, and she's walking and everything.

HEYMACH: That's great. Have you given any more immunotherapy [to that patient] then?

MIDATHADA: No.

HEYMACH: I'm the same way. I've had probably 4 cases of bad immune neuropathies, and I haven't wanted to give it again. But in at least 3 out of the 4 I can think of, they ended up having really good responses. I had 1 that I shared with the doctor at UT Southwestern with David Gerber, MD. This person was intubated and in the intensive care unit for weeks but when they got better, they did great in terms of their tumor. But we never gave immunotherapy again. It was too scary to us. I think the neurologic AEs are ones that I tend to not mess with giving therapy again.

Do people have other experience where they have gone back to give it with that sort of toxicity?

RAYMOND L. LOBINS, DO: I had a woman to whom we gave immune therapy and she had what looked like stroke-type symptoms where she had trouble moving basically half of her body. Her cancer went away but she's neurologically impaired now...we didn't see anything on the MRI. In her case, it's her left leg and to come into clinic she's in a wheelchair. She can walk with a walker. It's been a number of years; her cancer never came back.

HEYMACH: You can, in some cases, induce Lambert–Eaton myasthenic syndrome or at least a myasthenic-like syndrome. We've seen this with some cases [when] we give immunotherapy in patients with thymic cancers, where they get a Lambert–Eaton type or myasthenia gravis–like syndrome. Those are tough; sometimes they don't go away. We've had that experience where we ended up trying antithymocyte globulin or had to do steroids and everything else. Those are pretty frightening. In my experience, the neurologic complications are something that we never seem to get a firm diagnosis for. They seem to send a lot of antibody [tests], and I never see any of them come back positive. Out of all [AEs], that's one that I will never treat through. But we will treat through most other AEs or at least [continue] PD-1.