I appreciate the comments on my last post about how hopeful it was. I always love hearing a Lymphoma expert get excited about a treatment. And I love it even more when two experts are fighting over which of two great treatments is better.
Jacquline's comment was interesting: "I belong to several Follicular Lymphoma groups on various social media sites. There is a gentleman who swears that CAR-T cures fNHL. He apparently was "cured" because of it. I know someone who was not helped by CAR-T and eventually passed away. As with all treatments, some work for some people and don't work for others. That is why this article was so uplifting, it offers us many wonderful and promising treatments that are in the "pipeline". It is an exciting time, I feel fortunate to be living during all of this."
As much as I want to be as enthusiastic as the gentleman that Jacqueline describes, I'm with Jackie on this one -- hopeful but a little skeptical. I do think CAR-T is a miracle for a lot of people, and may very well cure them (whatever that means -- it's a complicated word). But I also know that there are a lot of patients who don't get a long-term benefit from it.
I want to focus on the word "cure." It truly is a complicated thing, and has a few different meanings. Some cancers are considered "curable," meaning there are treatments that have a very good chance of working, for a long time, for a large number of patients. I don't think there's an official definition of "cured" for cancer (not one that I can find). But there are certainly some patients who have received a treatment that lasts for their lifetime. That's "cured." And there are some cancers that have a larger number of patients in that situation. that makes the cancer "curable."
Follicular Lymphoma is, unfortunately, considered not curable. We just don't have treatments that work for many years on a large percentage of FL patients.
Here's where it gets complicated. Some Lymphoma specialists talk about patients being "functionally cured." In other words, they might not have entirely eliminated all of their cancer cells, but they haven't needed treatment again. Think about someone who is diagnosed at age 70 (pretty common), has B-R and then R-maintenance, and then a scan turns up some cancer cells at age 80. Not enough to need treatment again -- it's still growing slowly. That patient then dies a few years later, at age 84, about average life expectancy for the general population.
Was the patient "cured"? No -- there were still some cancer cells in their body. BUT, that B-R + maintenance lasted a very long time, long enough that they didn't need another treatment. Which is the definition of "cured," isn't it? This is called a "functional cure." Not technically cured, but living the same life as someone who was "cured."
(Incidentally, this is where I am now. 13+ years without treatment, but still had some bright spots on my last PET. I do not consider myself cured. There's always going to be a little part of me that expects it to come back.)
So while there aren't enough patients who will get treatment, and then go for their lifetime without cancer, to have FL be considered "curable," there are individual patients who may very well be "cured." But because the disease isn't considered "curable," it's hard to know for sure.
How does CAR-T fit into all of this?
Well, when CAR-T treatments were first approved, the clinical trial results were kind of 33/33/33. About one third of patients did not respond to treatment, one third had a response that lasted a year, and one third had a response that lasted longer than a year. (Those are very rough numbers.) Those numbers are improving, slowly, especially those whose response lasts longer than a year. In my last post, I write that Dr. Cheson says about 35% of patients in one study had a PFS of 5 years. In another follow-up, 10 patients with indolent (slow-growing) lymphoma who were given CAR-T had a median Complete Response rate of 5 years -- that's no cancer at all. The range for those 10 patients was between 1 and 114 months. So for at least one patient, it really didn't work at all. And for at least one more, it lasted almost 10 years.
To get back to Jacqueline's comment: the gentleman who believes CAR-T is a "cure" might very well be the patient who has had a 10 year response from it. The patient with the 1 month response would probably disagree.
So, as I said, a "cure" is complicated. Some patients might very well be cured.
But for me, the numbers are a little less hopeful. Too many patients who don't get the benefit.
Which isn't to say that there will never be a cure, or even that CAR-T won't be the treatment that turns out to be a cure. I'm still hopeful that the day, and the treatment, will come. I think there's even a good chance it will come during my lifetime. (Remember, I plan on living a very long life.)
In the meantime, I'll stay hopeful, keep learning all I can about this disease, and be ready when the time comes to choose a treatment to give me the best chance at a cure.
2 comments:
Hi Bob, I understand and respect your point of view, the data, although good, certainly does not seem disruptive to you to have to abandon a concept that has accompanied you for more than 13 years, the LF does not heal. Prudence, in a disease like cancer, seems to me an intelligent ally, no one can be reproached for being prudent.
It is also very interesting to establish the meaning of 'cure'.
If the cure of a disease is determined by its absence and by having a
Prognosis similar to that of the general population, we can conclude that many patients reach this point with different approaches.
Patients with a localized disease, with radiotherapy treatment are cured in 50%, ALO transplants cure more than 50%, AUTO transplants cure 30%, Conventional chemoimmonutherapy treatments 'could' also be curative for 35 % 40% of patients, time has yet to speak. It should be noted that some treatment options have a great toll, second neoplasms, graft-versus-host disease and other potentially important complications that distort the concept of 'cure'.
And finally CAR-T, no one is aware that there are many, many millions behind this technology, where one does not know where to place oneself when it comes to objectively analyzing the data and does not want to be the victim of excessive optimism because of guilt. of a propaganda campaign by the pharmaceutical companies themselves. At the same time, it is not lost on me either, as certain well-known doctors outside of the pharmaceutical companies who work with car-t try to minimize the effects of car-t in a kind of way to stick to conventional treatments.
The CAR-T trials are being carried out with highly treated people, with a rapid evolution, refractory to the treatments. POD24 is one of the worst expressions of LF and when you look closely at ZUMA-5 vs SCHOLAR-5 you realize that zuma-5 patients had no other options and still the data is incredibly good, you have to take a look. moment of reflection for that, they had no other options and their results are much better than those obtained with standard therapies.
What would happen in untreated patients? What results will you get? Would that lasting remission of 45% 50% of current hypertreated patients overcome? What kind of problems is car-t going to unleash in the long run?
The patient you are mentioning, champion of the internet cure, underwent CAR-T 7 years ago, with 9 treatments on his body, with transformation to aggressive ... Not only is he alive, he is also NED, this man is cured in my opinion.
https://clincancerres.aacrjournals.org/content/early/2021/08/10/1078-0432.CCR-21-1377
https://lymphomahub.com/medical-information/updated-results-from-the-zuma-5-trial-of-axi-cel-for-patients-with-relapsedrefractory-follicular-lymphoma
Thanks for the comment. It's interesting -- that post didn't start out as a reflection on the word "cure." It was actually going to be about an article in the ASCO Education Book about CAR-T. One of the sections is on "unaswered questions" -- things we still don't know about CAR-T. I started writing about that, and made what I thought was a short aside about Jackie's comment. But then I kept writing about it, and the post turned into something else, which happens with me sometimes. I might go back and write the "unanswered questions" post sometimes soon, because your comment really does bring that issue up -- there's still lots we don't know about CAR-T. And about other treatments, too. And, I would say, what it means for someone to be "cured" and be confident about that. What we really need, I think, is more biomarker research. There is some work on Minimal Residual Disease that might lead us toward being more confident in saying someone is cured, but it's still a ways away from being definitive. It's such a strange disease we're dealing with, and its strangeness is the thing that keeps us from knowing as much about it as we'd like to.
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