The main issue with older patients is actually several impacts: the immunosenescence phenotype that may alter the response to immunotherapy and the second big question is about the increasing number of autoantibodies with aging. We need to know if the number of autoantibodies can actually affect the toxicity of treatments.
What’s the current understanding in the literature of immunosenescence?
It’s still ongoing, probably that immunosenescence phenotype is not correlated with age but is actually correlated with poor response to immunotherapy. So we hope that with this study and with others coming we can have the answers to the question.
What’s the current understanding regarding autoantibodies and ageing?
It was actually from a paper ten years ago, around ten years ago, so it’s pretty old data. I think we need to work on that and probably to do prospective studies to really address the question once again. To my knowledge no studies are actually ongoing regarding the autoantibodies in aging.
What’s the current understanding of anti-PD-L1 immunotherapy with ageing?
Immunotherapy and especially anti-PD-1 or anti-PD-L1 therapy are clearly a good option for older patients because you have a broad spectrum of activity but you also have fewer toxicities, which is very interesting in frail patients. Since now no data has showed any lack of efficacy in older patients.
In our study we actually found more immune related adverse events of grade 2 or more in older patients compared to younger patients, with 33% incidence in older patients and 25% in younger patients. This result was actually statistically significant. But the type of toxicity and the spectrum of toxicity was actually very different between the two groups. We saw more skin toxicity in older patients and also more liver toxicity compared to younger. In younger patients actually we found more GI toxicity, endocrine toxicity and also pancreatic toxicity. So the spectrum is different and we can see that in older patients the type of toxicity is not very threatening for them. So it’s reassuring to see that even if they have more toxicity we can still give them the immunotherapy.
How are comorbidities in older patients managed?
We actually need to work on that because we know that in a recent paper they showed that cardiovascular medical history can be associated with more toxicity, especially cardiac toxicity, through immune checkpoint blockers and especially in combination. So in older patients we need to find correlation between comorbidities and also toxicity. In our study we did not find any correlation but we are actually working on that to go deeply in the subject but obviously this is a very important question. Frail patients can also benefit from immunotherapy, we just need to identify the right patients for the drug actually.
This is where screenings and assessments are useful?
Exactly. So there are many studies ongoing actually, prospective studies, which include geriatric assessment and geriatric parameters to correlate to toxicity and also to efficacy but we don’t have, unfortunately, the results yet but it will be coming in the next month, I think.