R-Squared and the C Word

Interesting video (with transcript) from the Oncology Learning Network last week. It's called "Dr Strati Highlights Lenalidomide Plus Rituximab for FL," and it features Dr. Paolo Strati from MD Anderson Cancer Center. He talks about the use of R-Squared (Lanalidomide + Rituxan) as a first treatment for Follicular Lymphoma. 

This isn't new research that he's discussing. (This seems to be a discussion of some research from ASH in December, which was a 10 year follow up of a study of R-Squared. The research has been around for a while, in some form or other.)

A quick recap of that research (though the results of the research aren't really what I want to focus on here): There were 70 patients enrolled in the study ( a fairly small number), and after 10 years, 70% of them were still treatment-free after 10 years. There was no common feature of the disease (like a biomarker) that could predict which patients would have such a long time without treatment, though it was much more likely to happen if the patient had a Complete Response to the R-Squared. 

All of that is great, and I've talked about it before. What really caught my eye was something Dr. Strati said about the "c word":

"What we saw was with immunotherapy, up to 70% of patients were still treatment-free 10 years after initial treatment. We tend to say that FL remains incurable. Findings like this challenge this paradigm."

Just to be clear, he says it again soon after:

"The most surprising outcome, in my opinion, was very high disease-free rate (of) 10 years after initial immunotherapy. As mentioned before, we keep saying that patient with FL cannot be cured, but in immunotherapy, and more recently also cellular therapy, may completely change this narrative."

Now, I have also given my thoughts here about the "c word," and the idea of a cure for Follicular Lymphoma. I think we're moving our way towards a cure, though I personally have a hard time thinking about FL being curable.

Let me be clear about that -- for me, it's a personal thing. I've lived with the idea that Follicular Lymphoma is not curable, that I will likely have it for the rest of my life, and that treatments are available now and will continue to become available over time that will help me deal with my FL, for as long as I have it. It's really hard for me -- again, personally -- to get past that. I haven't needed treatment for over 12 years. I'm not cured -- I was just looking at the electronic notes from my last oncology visit, and I was reminded that my last scan (several years ago) showed some small amount of disease still lurking around in there. I might go another 40 years and not need treatment. But I'll probably still be eating my 90th birthday cake, thinking, "Gosh, that FL could come back any time...."

Dr. Strati's comments highlight for me just how complicated it will be to define what a "cure" is for FL. Is it that 70% of patients go longer than 10 years without treatment? Because that's happening not for a lot of R-Squared patients, obviously, and for some CAR-T patients with leukemia. 

As I mentioned when I wrote about problems with inhibitors recently, I think having more durable treatments (that is, treatments that give patients long periods between treatments) will become much more common as we move along. It's going to be seen as an important, achievable goal. Doctors and patients aren't going to be satisfied with an exciting new treatment that gets at FL cells in a new way, if that treatment only lasts for 18 months. There are going to be other, better options available. there already are.

Which brings up one of the big complications of saying an FL patient is "cured" -- our median age at diagnosis. Most FL patients are diagnosed in their 60's. If a patient is diagnosed at age 70, has R-Squared or CAR-T and never needs another treatment, and then dies of something else at age 80, were they "cured"? Some lymphoma experts call this a "functional cure" -- maybe not a long enough time to measure whether or not they would have continued to live without treatment, had they been diagnosed at a younger age. But, on the other hand, they died at or near the average lifespan for the general population, without ever needing treatment again. That's pretty close to "cured," isn't it? It's what we all hope for, right?

And since a very large portion of FL patients are diagnosed late in life, it's very likely that many more of them will be "functionally cured" in the years to come. 

But that makes it had for someone like me, diagnosed at age 40, to wonder if and when I'm cured. Like I said, 90 candles on my birthday cake, and I'll be making the same wish.

The good news with all of this -- to get back to Dr. Strati -- is that we have treatments with long durability, and more coming. When I say I think that's going to be the goal of treatment in the future, keep in mind that I'm saying that as a non-expert. Just my opinion. But we're seeing more of that long durability with new treatments, and I suspect we will see more of it still. 

That's a very good thing, no matter what word you want to call it.