This is Mark Kris from Memorial Sloan Kettering, speaking today about an emerging issue in our treatment of patients with lung cancers, and that is the use of immune checkpoint inhibitors in patients with a history of prior autoimmune disease. Many of us know that these patients were, by and large, excluded from clinical trials, but not completely. In the pivotal trial by Reck[1] comparing pembrolizumab with chemotherapy, autoimmune disease itself was not an exclusion, but history of autoimmune disease requiring treatment in the 2 years prior to therapy was an exclusion. Theoretically, some people with autoimmune diseases were in that study.
Recently, a paper by Leonardi was in the Journal of Clinical Oncology, talking about their experience in 56 patients with a history of autoimmune disease who received a checkpoint inhibitor. In that group, 45 of the 56 were not symptomatic, but 13 had a flare of their autoimmune disease. Of those 13, four required no treatment while the others recovered after receiving treatment that was not complex.
I think message one is that having a history of autoimmune disease does not necessarily impart a flare if indeed a immune checkpoint blocker is being used. Second, in those patients who have a flare, the [typical] management strategies that are used for the autoimmune disease can be used. I should say, though, that in the Leonardi paper, there were very few people with Crohn disease on an anti–tumor necrosis factor (anti-TNF) drug like infliximab, for example, or people with multiple sclerosis receiving immunosuppressive therapies. Those people were, by and large, not included in the study. The message here is that if the therapy is right for the patient, it should not be categorically thrown out.
How do you decide to do that? The first thing is, please make sure that there is no better option or no medication that has a greater likelihood of benefit. Go down the list of possibilities for your individual patient, see if there is something with a better track record, and go for that.
The second thing I do is try to see if there is a higher likelihood of benefit for an individual patient I’m recommending these therapies to. In my practice, I make sure to get both programmed death-ligand 1 (PDL-L1) and tumor mutational burden to see if there is another target that perhaps would be more likely to provide benefit, and to see if there are specific abnormalities that would suggest benefit from the immune checkpoint blockers. That would help change that risk-benefit ratio more in favor of trying the drug.
I think the third thing is that you need to have a very clear goals-of-care discussion with the patient and have total agreement with the patient and their family about what these risks are. The risks are likely to be low but not zero, and more truly than not they are unknown. The more serious the autoimmune condition, the less we know about it, at least in the published literature among people with lung cancers. Again, have a very clear discussion with the patient.
Patients who have a serious autoimmune disease who have had flares of their disease before know that immunosuppressive drugs can work. Different than with [complications like] febrile neutropenia or neuropathy, there is, in essence, an antidote for those symptoms. An anti-TNF drug, immunosuppressive agent, or steroids can be given should patients have symptoms [of their autoimmune disease]. That gives some comfort to the patient and changes the risk-benefit ratio.
The last thing that is very important is to mobilize the patient’s team. Most of us do not have the current knowledge of how best to manage a lupus or multiple sclerosis flare. It is absolutely clear that the patient’s doctor who handles those complications and has been prescribing those drugs be involved and be comfortable with stepping in if indeed a flare is created.
Immune checkpoint blockers may not be off the table in patients with a history of autoimmune disease. There are many considerations, but at the right time, they can be a useful adjunct to care and there are plenty of reports in the medical literature that they can be helpful. This is something to think about. Again, our job as medical oncologists has gotten easier in that we have more things to recommend to patients and there are better results. But it’s gotten harder, too, because the decision-making is much more difficult. But that’s okay. If we can make our patients have a better result, that is what we are here for.
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