In this “Science Simplified” series, we’ll be sharing insights from the latest research presented at the American Society of Hematology (ASH) conference in December 2025. Each article explains what was studied, what was discovered, and what it could mean for people living with follicular lymphoma, without complex scientific language.
In this edition, the article has been split into two parts: the first looks at the latest advances in T‑cell engaging therapies (bispecific antibodies and CAR-T cell therapy), while the second explores other targeted treatment options. The large amount of research in this area reflects the urgent need for better treatments for people whose follicular lymphoma comes back.
Our aim is simple: to make the latest research understandable, relevant, and useful to you.
Targeted therapies are treatments designed to focus on specific features of cancer cells that help them grow or survive. By targeting these features more precisely, these treatments aim to control the lymphoma while reducing damage to healthy cells.
For those living with FL, targeted therapies are helping expand the options available after relapse. These therapies may offer effective chemotherapy-free alternatives, with different side effect profiles and, in some cases, more convenient ways of taking treatment.
There are several novel targets and treatment methods being studied in FL and other blood cancers, however most are in very early stages of research. Below we highlight some of the most promising studies that were presented at ASH 2025 – most of which are in early phase clinical trials stage.
BTK (Bruton’s Tyrosine Kinase) is a key signalling protein in B-cells (where FL grows). In healthy bodies they signal to the B-cell its natural life cycle of growing and dying. In FL these signals get confused and signal the B-cells to keep growing and stay alive. BTK inhibitors shut down these signals.
In the ROSEWOOD study, a landmark phase 2 clinical study, researchers compared a combination of the BTK inhibitor zanubrutinib with the antibody treatment obinutuzumab (an alternative to rituximab), against obinutuzumab on its own. After around 3 years follow-up, study results showed response rates to be almost twice as high for patients receiving the combination treatment. Importantly, the time before another treatment was needed increased from around one year to just over four years. Side effects were more frequent, partly because people stayed on treatment longer.
These impressive results led to the accelerated approval (in the US) of the combination in 2024.The makers of the treatment have not shared if and when they will seek approvals for this to be available in other countries but we will update the community when we have news. A larger follow up study, (the phase 3 MAHOGANY study) is now underway to confirm these findings by directly comparing the zanubrutinib + obinutuzumab approach with another commonly used treatment combination lenalidomide + rituximab (known as R2) for relapsed follicular lymphoma. It is not yet clear when this treatment option may be evaluated for use in other countries and regions – watch this space.
Golcadomide is a new type of immune‑modulating therapy known as a “CelMOD” – related to lenalidomide.
In an early phase study of 63 patients with R/R FL who had already received at least two treatments:
A large clinical trial (GOLSEEK‑4) is now comparing golcadomide + rituximab with several standard options, including R² (lenalidomide + rituximab), BR (bendamustine + rituximab), and R‑CHOP (Rituximab + chemotherapy combination). This drug is not yet approved in any country and the results of this study will be published before the manufacturer decides if and where to seek regulatory approval. Golcadomide is also being tested in combination with bispecific antibodies in broader B‑cell lymphoma studies.
Amulirafusp alfa works differently from traditional antibodies. Like other drugs it targets CD20 (the protein that coats B-cells), but this also works on CD47. CD47 is another protein on the surface of cells but this signals “don’t eat me” allowing cancer cells to hide from your immune system.
This drug blocks this signal and while previous CD47‑targeting drugs have struggled to show benefit in the clinic, these results mark an exciting step forward:
This very small early phase study of only 38 patients showed intriguing results, and we look forward to seeing progress in larger trials next.
Another new area of research targets BCL6, a protein lymphoma cells rely on to stay alive. An oral drug called BMC‑986458 can break down BCL6 directly, weakening lymphoma cells. Early studies suggest this treatment can reduce BCL6 in some B‑cell lymphomas, but research is still at an early stage. Future trials will explore whether this approach could be useful for people with follicular lymphoma.
Taking both parts of this article into consideration, the research presented at ASH 2025 shows that progress in R/R FL treatment is not slowing down. Scientists are working to combine therapies in smarter ways, improve safety, and better understand which patients are most likely to benefit from each treatment.
New therapies are:
As research continues, many of these emerging treatments may help people stay in remission longer. The treatment landscape for FL continues to evolve, moving us closer to more personalised, more effective care.
Read the first part of the Article here:
Watch our Webinar on Choosing your next treatment here: https://www.theflf.org/previous-webinar/choosing-your-next-treatment-what-follicular-lymphoma-patients-should-know/
For the full technical report on ASH 2025 learnings, find our Chief Medical Officer’s article here: https://www.theflf.org/wp-content/uploads/2026/01/CMO-FLF-JAN2026-report.pdf
Acknowledgements
These “Science simplified” articles on the learnings from ASH 2025 are supported by sponsorship from AstraZeneca, Genmab, AbbVie, Ipsen and Incyte. All of the above have had no influence on, control of, nor input into the development or content of any article.
This article is for information purposes only, and we recommend that you speak with your healthcare team if you have any questions around suitability and regional accessibility of therapy options.
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