I'm doing another ASH post, this time looking at several ASH presentations at once. I'll look at them through the lens of the Leonard List.
The Leonard List comes from Dr. John Leonard of Weill Cornell Medicine. Dr. Leonard is one of the best-known Lymphoma specialists in the U.S., and every year he publishes his List of the 10 most interesting abstracts from ASH, about a week or so before the meeting happens. He discusses them, plus a few bonus ones, on the "CancerCast" podcast from Weill Cornell. You can listen to the full podcast episode here; there's also a transcript if you want to read along or translate it more easily.
I always enjoy listening to Dr. Leonard go through his list, especially when I have already written about something that he finds interesting. I will only focus on his choices that are related to Follicular Lymphoma, but if you are interested in other types of blood cancer, I encourage you to listen to or read the whole podcast for some other great commentary.
The first time FL makes the lost is at number 7, and it actually shows up twice -- Dr. Leonard lists two related abstracts as 7A and 7B on his list.
7A is "3749 Subsequent Primary Malignancies in Patients with Indolent B Cell Non-Hodgkin Lymphoma Receiving Frontline Bendamustine Rituximab Therapy.” In this presentation, the researchers look at the records of 6284 patients with slow-growing lymphoma (inlcuding FL, but some others, too) who received Bendamustine as their first treatment. They were interested in how many patients went on to develop another cancer after the treatment. According to their research, about 15% of them developed a second cancer, with a median time to diagnosis of 2.36 years, including lung cancer, digestive system cancer, and other blood cancers. Did the Bendamustine cause the other cancers? It's hard to say, as Dr. Leonard says, since many of the patients went on to other treatments, including radiation and Stem Cell Transplants, or simply have immune systems that make them susceptible to other cancers. The takeaway, says Dr. Leonard, is not that Bendamustine is bad or that one treatment is better than another. "To me, the takeaway here is that patients need to
be monitored for other cancer. And I think that that is a really
important issue for all lymphoma patients. You have to think about lung
cancers and GI cancers and monitor for blood cancers, breast cancer, et
cetera. And so to me, the takeaway actionable item here is really just
to make sure that patients are followed and get the appropriate
cancer-related screenings because they are at risk for other cancers." That's an important distinction. We're all at higher risk for other cancers; the scar on my scalp is a reminder of that. Be sure to keep up with cancer screenings.
7B is related: "3009
Impact of Prior Bendamustine Exposure on Bispecific Antibody Treatment
Outcomes in Patients with Relapsed/Refractory Follicular Lymphoma." This one looks at FL patients, specifically, who have had Bendamustine, and the went to receive a bispecific antibody. Since Bendamustine can affect T cells, and bispecifics work by engaging T cells to go after the cancer cells, the researchers wanted to know if receiving Benda would make the bispecifics less effective. This is tough, as Dr. Leonard points out, becuase there can be lots of reasons why a treatment doesn't work, and like 7A on the list, lots of patients in this study received other treatments besides Benda. No matter -- the patients in the study didn't seem worse off than other patients receiving Benda when they went on to receive a bispecific. By the time most patients receive a bispecific after Benda, it's been at least a year, and their T cells have had time to recover. It's one less thing to worry about if you've had Bendamustine.
Next on the list is number 2, which isn't directly about Follicular Lymphoma, but it's really interesting to me. It's "2267 Toxicity Outcomes in Phase 1 Lymphoma Trials: Variable Reporting with High Use of Minimizing Language in Published Abstracts at International Conferences." I'm especially interested in this because I have a real interest in the language we use to talk about cancer, but also because this research affects the way I write the blog. The researchers looked at presentations from major cancer conferences (like ASH) that reported results from phase 1 clinical trials. They were interested in how safety was discussed in these presentations. There's kind of a tension here. On the one hand, phase 1 trials are all about safety; the whole idea is to figure out what dose of a new treatment will work well but do the least harm. On the other hand, someone presenting data about a new treatment wants to make it sound as good as they can, so there's a temptation to be more positive than they should be. As the research points out, you'll se a lot of language like "tolerable" or "safe" or "manageable" when talking about side effects, but there's no accepted definition for what those words mean. So it's important to look carefully at the numbers and not just rely on the language being used.
(This hits home for me, as someone who writes about clinical trials all the time. I have to force myself sometimes to bring up the potential safety issues. Just a couple of days ago, my wife was reading my last post, in which I mention that several patients died during the study. She really doesn't like to read about that. I pointed out that, first, a number of those patients died because the study happened during the Covid pandemic and had weak immune systems, something I didn't mention in the blog post, and second, it's important information and needs to be mentioned. I remember a few years ago someone talked about me on a Facebook group, and someone else said I could be too negative sometimes in my writing. It's true, I can be negative but I try hard to be just the right amount of negative, not too negative. I don't see much point in not giving you the potential bad with the good. False hope isn't good for anyone. Every treatment comes with some trade off,and we need to remember that.)
Number 1 on the Leonard List is about Follicular Lymphoma: "1652 Outcomes in Early Relapse of Follicular Lymphoma Versus Early Histologic Transformation Following Firstline Immunochemotherapy in Follicular Lymphoma." In this presentation, the researchers look at the two situations that are most troubling for FL patients: transformation and POD24. First, POD24 stands for "Progressio of Disease within 24 months." FL patients with POD24 are those who have received immunochemotherapy (like R-CHOP or R-Benda) and then have their disease get worse with the next 24 months. About 20% of FL patients will fall into this category. Transformation happens when our nice slow-growing cancer turns into a different type of lymphoma, one that is fast-growing. Both POD24 and Transformation lead to a lower Overall Survival rate. The researchers here show some evidence that there is overlap in these two groups. That is, many patients with POD24 also have transformed disease. But in looking at the bigger picture, they are being counted twice. In other words, look at 10 FL patients and see that 2 have POD24 and 2 have Transformed disease, but really it's one of each, plus one with both -- 3 patients instead of 4. That matters when statistics are put together about POD24 -- maybe the Overall Survival numbers are better of patients with Transformed disease are separated out from those POD24 patients who have not transformed. Dr. Leonard wants to see the details of the research next week, but thinks this could put even more emphasis on Transformed disease. POD24 is really a label that needs to be separated into at least two groups. It will be interesting to see what the Lymphoma experts have to say about this presentation later on. It's a big deal if it ended up #1 on the Leonard List.
Dr. Leonard also gives 5 bonus presentations on the podcast, and FL makes an appearance here, too. It's one that I have already written about a few days in the blog-- "782 Travel Burden and Travel Costs of Bispecific Antibodies in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma and Relapsed/Refractory Follicular Lymphoma. I am pleased that Dr. Leonard chose a study that looks at Quality of Life and the time and money that comes with treatment, even apart from the cost of the treatment itself. As Dr. Leonard says, "My takeaway is just that this is a factor that is interesting and important to our patients and something we don't take into account and probably we should be thinking about a little bit more. Taking 50 or 80 hours or longer out of work or other things you have to do if you're a family member or a patient, and the cost of $2,000 and $3,000 in some cases for patients to travel, this is a burden of care that we don't always think about in our practice and probably should be paying some attention to."
Excellent analysis, Dr. Leonard.
So there's the Leonard List for 2024. Follicular Lymphoma played a pretty big role this year, bigger than most years. I'm pleased I was able to describe a few important studies all at one time for you.
I'll try to get one more preview in before the meeting starts at the end of the week. Once that happens, the previews are over and the reviews begin. I'll report on what the cancer news websites are excited about, and what the experts have to say in the days and weeks after the meeting.
Stay tuned for more.
