Immunotherapy

So I think it's intriguing data.

I think it's also interesting that Immunotherapy may be differently effective in stage four disease or stage three disease, the earlier disease setting.

So I think, of course, it would be wonderful if we have another biomarker.

It's not PD-L1 expression, but something beyond mismatch repair that may determine whether we can enrich that population that's proficient in mismatch repair and get a greater benefit from them.

If the PD-L1 is less than 1%, chemo-IO, with a notable point that dual checkpoint blockades, such as ipinevo plus minus chemo, may confer a particular long-term OS benefit in the PD-L1 negative group.

Specific backbones for histology with all the IOs, we kind of went over these, but let's go over them again.

For adenocarcinoma, carboplatin plus pemetrexin.

And the alternatives can be carboplatin plus paclitaxel plus IO.

Cancer immunotherapy teaches the body to fight tumors.

Cancer is cunning, often evading the immune system's watchful eye.

Immunotherapy seeks to awaken the body's defenses, teaching them to recognize and destroy malignant cells.

One method uses checkpoint inhibitors, drugs that remove the breaks cancer places on immune cells.

Others involve vaccines that train immunity against specific tumor markers.

For some patients, especially with blood cancers, the results have been dramatic, complete remission where all else failed.

These treatments can be grueling and costly, but they represent a profound shift in strategy.

Instead of poisoning tumors with radiation or drugs, enlist the immune system itself Immunotherapy blurs the line between medicine and biology, reminding us that the most powerful weapon against disease may already exist within us, waiting to be guided into action.

And of course, that's what happened.

But I remember one of the very first things I was thinking about was just the question you brought up, which is what about people with paraneoplastic syndrome? Do they get worse with IOs? Now we have tarlatumab.

And I still, it's almost 10 years later, and I still am not sure I have an answer.

Do you have an answer? Do you think that paraneoplastic, I mean, obviously the tumor gets better, the paraneoplastic syndrome should get better.

Endocrine, perineoplastic syndromes in my mind, I think those patients are certainly eligible for immunotherapy and T-cell engager therapy.

And they were included in some of those trials and then they weren't excluded is a better way to put it.

But I was just curious whether, again, IOs make it worse.

I mean, it doesn't necessarily prove anything.

She's now permanently discontinued because of her most recent event.

Melinda, do you believe this comes up in all the diseases and cancers where IOs are used? Do you think there's a relationship between autoimmune toxicity and treatment benefit?

Yeah, it's really interesting in this patient.

She had really major liver metastasis.

I'm very intrigued by, you know, that response in her liver.

And so, you know, I think that You know, there may be something to that, right? So she had a few serious, really uncommon adverse events, but has had this really excellent response, which she's maintaining at this point.

I think in lung, they've shown a correlation that people get COVID vaccines and benefits from IOs.

I don't know, maybe stimulating the immune system might be something else that might be a factor here.