CAR-T and Cures

The big news this week in the Lymphoma World is an article that was published in the New England Journal of Medicine yesterday. It describes long-term follow-up of patients with B Cell Lymphoma, including some with Follicular Lymphoma, who received CAR-T. The results were very encouraging, and that "C word" ("cure") is being used again. More on that after I describe the article. 

The article is called "Ten-Year Outcomes after CAR T-Cell Therapy for B-Cell Lymphomas." It presents results from 38 patients -- 24 who were diagnosed with Diffuse Large B Cell Lymphoma and 14 with Follicular Lymphoma, all of whom had refractory/relapsed disease (so they'd had at least one previous treatment).  They received just one infusion of the CAR-T treatment Tisagenlecleucel (also known as Tisa-cel or Kymriah) a median of 10 years ago. It's a pretty small study, but it has some important results.

I'll stick to the FL patients' results, since that's what most of us are here for. Almost half of the FL patients in the study had gone 10 years without a relapse. And for patients who had gone 5.4 years without a relapse, they continued to be Lymphoma-free after that. Most relapses occurred within the first year after treatment. 

I'll put this into a little bit more context. Early research on CAR-T treatments had kind of a 33/33/33 breakdown. For about 33% of patients, the treatment didn't work at all. For another 33%, it worked for about a year or less. And for the final 33%, it worked for more than a year. Those numbers aren't exact, but they're roughly accurate, and it's how I often think of CAR-T's effectiveness early on. Those numbers have also gotten better over time. So now, in this study, we're at 50% rather than 33% for long-term effectiveness. I can't see a breakdown for the other 33/33 groups, but they have to be smaller. 

Of course, CAR-T isn't perfect; half of the patients in the study did not have good long-term results. And there were side effects, too, to deal with. Two of the 38 patents had long-term low white blood cell counts, but there were no cases of long-term low red blood cells or ongoing anemia or low platelet levels. But perhaps more importantly, 9 patients developed a second cancer (including 3 with Acute Myeloid Leukemia, 2 with prostate cancer, 2 with lung-cancer (possible smoking-related), one with melanoma, and one with a T-cell lymphoma that affects the skin. All together, that is a higher incidence of cancer than the general population, though it is similar to the incidence for Lymphoma patients who received traditional chemotherapy.

What's most interesting about this to me is a press release from University of Pennsylvania Medicine, where the research occurred. Here's where the "C word" comes in:

Most relapses occurred within the first year after CAR T cell infusion, supporting the hypothesis that patients who experience a long-term response to CAR T cell therapy may be cured. "As oncologists, we use the word ‘cure’ with great care, but I am increasingly confident that CAR T cell therapy has the potential to cure a meaningful number of patients with B-cell lymphomas,” said senior author Stephen J. Schuster, MD, the Robert and Margarita Louis-Dreyfus Professor in Chronic Lymphocytic Leukemia and Lymphoma Clinical Care and Research and director of Penn’s Lymphoma Program. “At the same time, our work is far from done. This therapy does not yet work for everyone, and we are committed to understanding why so we can continue to improve the next generation of CAR Ts."

It's interesting to see both of things happening here -- that the word "cure" is used, and that the researcher is cautious about using it.

It certainly brings to mind the research that was published a few months ago that suggested a 15 year follow-up after R-CHOP might show that some patients were cured. I was hesitant to use the word "cure" then and I'm still hesitant to use it now. 

That's not to say it isn't possible, but it's still hard for me to wrap my brain around, 18 years after I was told it was incurable.

Last month, the Follicular Lymphoma Foundation published a blog post called "Could Some People with Follicular Lymphoma Be Cured? New Evidence Sparks Careful Optimism." It reports on an interview that the FLF's Chief Medical Officer, Dr. Mitchell Smith, conducted with the lead researcher on that study, Dr. Jonathan Friedberg. (They are both Lymphoma Rock Stars, by the way. I'm going to start using that label again, I think.)

I'm actually quoted in the blog post. And since I love to quote myself, here's part of what I said: "It opens up a whole new way for patients to think about FL: that some of us might be cured. I was diagnosed over 18 years ago… and I haven’t needed treatment since. I might fall into that category of patients who are cured, and yet I still have that small little bit of doubt and fear in my head."

I think that explains my feelings pretty well. Here's another quote from me: "It's going to take some courage from both doctors and patients to change our way of thinking...but what an exciting future it will be."

I think that explains things pretty well, too. I suspect we're going to see more long-term studies of FL treatments very soon. They are a lot easier to conduct than clinical trials -- all of the data is already collected. And I suspect we'll see a lot more doctors using the word "cure" as a result.

What an exciting future it will be, indeed. We have lots to look forward to.