This post is the next one in a series of previews for the ASH meeting, one of the largest gatherings of blood cancer specialists in the U.S. The abstracts (or summaries) of the presentations come out a few weeks before the meeting, so while they don't give all of the details of the research, they do give enough for me to see if it is interesting or significant enough to focus on and write about.
For this post, I'm going to do something I have done in the past -- look at The Leonard List. Every year, Dr. John P. Leonard, a Lymphoma specialist in New York, gives a list of what he thinks are the Top 10 abstracts related to Lymphoma at the year's ASH meeting. It's always interesting to see which of his Top 10 are focused on Follicular Lymphoma, and which of them were on my list as well.
(And, to be clear, Dr. Leonard is one of top Lymphoma specialists in the world. I'm not saying my list is as accurate as his, in terms of significance of the abstracts. If it's important to you to know which research at ASH really matters, go with Dr. Leonard, not with me. I'm just a guy with a blog.)
These will be shorter discussions from me than the previous ASH posts, since we have several to talk about.
Number 10 on The Leonard List is abstract #52: EZH2 and CREBBP mutation status identify a subset of patients who benefit from bendamustine- over CHOP/CVP-based immunochemotherapies in follicular lymphoma: Findings from the GALLIUM trial and validation in a large international cohort. This one was actually on my list of abstracts to review. It looks at data from the GALLIUM trial, which involved 1202 patients with Follicular Lymphoma who had not been treated yet. Half received Rituxan + chemotherapy (either Bendamustine, CHOP, or CVP) and the other half received Obinutuzumab + chemo (the same three possiblities). A few years ago, data from this trial showed that Bendamustine led to longer Progression-Free Survival than CHOP or CVP, but also showed that Bendamustine led to more high grade infections than the other two chemos. This led to the idea that Bendamustine might make CAR-T less effective if the CAR-T comes later, since the Bendamustine affects the T cells that CAR-T relies on. For this presentation, the researchers look at gene mutations in the data they collected to try to identify which patients might benefit from taking Bendamustine, and which might be better served with a different treatment. They found that mutations in EZH2 and CREBBP could help predict success with Bendamustine. Patients with CREBBP and wild-type EZH2 benefit most from Bendamustine, with much longer PFS and Overall Survival than other patients in the trial. The others had similar PFS no matter which chemo was given. Still some more research needed to confirm this, but it's they type of biomarker research that's been so difficult to find lately.
Number 8 on the Leonard List is abstract #5515 CD19 expression is preserved following CD19-directed monoclonal antibody therapy with tafasitamab. This is a fairly small study that focuses on one of the problems that comes with CAR-T. If you've been reading the blog for a while, you know that many FL treatments rely on targeting proteins on the surface of the cancer cell. Rituxan, for example, targets the CD20 protein, which is very common on B Lymphocytes (the white blood cell that turns cancerous in FL). Another common protein is CD19, and that's the one that CAR-T goes after. The problem is, for about 30% of CAR-T patients who relapse after CAR-T treatment, their B Lymphocytes no longer have the CD19 protein, which means a whole bunch of FL treatments won't work on them anymore (though there are plenty that will work since they don't work by targeting that protein). The research in this presentation looked at Tafasitamab, an anti-CD19 monoclonal antibody. The research looked at patients who had one of several B Cell cancers, including FL. They wanted to know if taking Tafasitamab had the same effect as CAR-T, resulting in losing the CD19 protein. They found that most patients did not lose the protein. The conclusion has to do with sequencing of treatments -- patients who are CD19-positive should receive a treatment like Tafasitamab first, and then CAR-T if necessary. It's a small study and a small piece of the puzzle, but for those of us with a cancer that often returns, that kind of planning is important.
Number 4 on The Leonard List is abstract #5385 Evaluating the clinical outcomes of GLP-1 receptor agonists in untreated indolent non-Hodgkin's lymphomas undergoing active surveillance. I'll be honest -- I talked to my wife about this one and I wasn't sure I wanted to even write about it, for reasons you will see. But I'm going to follow The Leonard List here and add my commentary about it. This presentation looked at the possible effects of GLP-1 agonists (that is, medications like Ozempic, Wegovy, and Mounjaro) on watching and waiting. These are given to help control diabetes and, increasingly, for weight loss. The research looked at patients with indolent, slow-growing Lymphomas (including FL) who had been taking a GLP-1 before or after their cancer diagnosis, and who were able to watch and wait. In looking only at the whole group, they found that patients who had received GLP-1, about 17.3% required treatment during the study, versus 20.3% who had not taken a GLP-1. The patients in the GLP-1 group had a lower risk of acute cardiac events including myocardial or heart attack (4.9% vs 7.3%) and a lower risk of heart failure (10.6% vs 15.2% ). Looking only at FL patients, the results were similar, but also included analysis that showed that there was "a reduction in those who progressed to DLBCL" (which I assume means transformation) -- 4.5% vs 8.3%. The abstract does not say why the GLP-1s might contribute to these results, though in the introduction, they hint that it might be more about weight loss and controlling diabetes than about the medication acting on the cancer cells directly. Both contribute to inflammation and heart issues, so reducing them will reduce other problems.
So why am I reluctant to write about it? Well, I'm always extra careful when I write about something that that's kind of "in the news" and is also controversial, and I think both of things are true about GLP-1s. The one thing I absolutely do not want anyone to think is that taking a GLP-1 will somehow cure their FL. There's no evidence in this study that such a thing would happen. This study looks at a very particular population -- FL patients who are watching and waiting -- and makes conclusions about particular things -- increasing time to treatment, reducing heart issues, and possibly reducing transformation. Should you be taking a GLP-1? I have no idea. Talk to your oncologist about how much they know about whether or not it will have an influence on your cancer, and talk to your other doctors about whether it will have an effect on any other health issues you are experiencing. Your doctors are the best people to help you make those decisions. As I wrote above, I'm just a guy with a blog.
(I'm guessing this is going to be one of those ASH presentations that people talk about after all of the details are presented at the meeting. I'll share if I see anything with good analysis.)
Finally, Number 2 on The Leonard List is abstract #117 "Lymphovision: A lymphoma-specialized foundation model for histology-based lymphoma classification and subtyping." I already wrote about this one. I guessed number 2 correctly!
So that's The Leonard List for this year. In the past, Dr. Leonard has gone into a little bit further detail about his picks during a special podcast episode. However, that podcast was sponsored by his old institution, and he's switched jobs since last year. I haven't seen any notice on his Twitter/X feed that he's got a podcast episode coming up, but I'll keep looking. I'll post a link if there is one,
The ASH meeting starts very soon -- it runs from December 6 to 9. That means we'll start to see press releases, articles, and videos with more detail about some of the presentations. That means I might be moving soon from "ASH Preview" to "ASH Review," but I'll probably still be sharing some ASH content either way for a few more weeks. So stay tuned.
