Recent Advancements in Frontline Therapy for Patients with R/R Follicular Lymphoma
At the 2025 Lymphoma, Leukemia & Myeloma (LL&M) Winter Symposium in Miami, Florida, Joanna Rhodes, MD, MSCE, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, discusses advances in frontline treatment, including bispecific antibodies and T-cell therapies, for patients with follicular lymphoma.
Transcript:
Hi. I am Dr Joanna Rhodes from the Rutgers Cancer Institute, New Brunswick, New Jersey, and I'm at the LL&M Winter Symposium in Miami.
Today, I spoke about advances in upfront treatment for follicular lymphoma. I think that this is a really exciting topic because while we do have amazing treatments for our patients with follicular lymphoma that are very well-established, there's always room for improvement, particularly for patients with high-risk disease.
I highlighted 4 key studies that have been presented over the course of the last year at ASH and at ASCO highlighting the use of our agents that are approved in the relapsed/refractory settings, such as tazemetostat in combinations with established treatments such as bendamustine rituximab.
The first study we talked about was a Big 10 collaboration of bendamustine rituximab plus tazemetostat for patients with high tumor burden follicular lymphoma. This phase 2 study demonstrated that the combination of 3 cycles of bendamustine rituximab with tazemetostat, followed by 3 cycles of tazemetostat plus rituximab, led to very high overall response rates with all 20-some-odd patients treated on the study having 100% percent rate of CR, complete response.
That's exciting data. Bendamustine rituximab has been a well-established, well-utilized treatment strategy for frontline follicular lymphoma, but again, if we can minimize the use of toxic agents such as bendamustine, I think our patients have the potential to do better long-term, potentially with fewer side effects during and post-treatment in the survivorship era.
The next study that I highlighted was looking at subcutaneous mosunetuzumab in the frontline setting for follicular lymphoma. The MYTHIC study, mosunetuzumab is already FDA approved for patients that have received at least 2 prior lines of therapy for follicular lymphoma and is very well established as a treatment in that setting. I think there's a lot of excitement around the bispecific antibodies, and so the use of these in the frontline setting makes a lot of sense, particularly for a disease that we know immunomodulatory agents work so well in.
This study demonstrated that there are very high overall response rates, approximately 90% rate of CR for patients treated with 8 to 17 cycles of subcutaneous mosunetuzumab, and overall, it was very well-tolerated with limited amounts of CRS, about 50%, most of which was grade 1 and was with the first dose of treatment. That's important because for our patients with follicular lymphoma, outpatient treatment I think is what our goal should be. So if we can minimize the treatment risks and minimize hospitalizations for these patients, particularly in the frontline setting, that's of utmost importance.
Next, we looked at a study that we're actually running in conjunction with several other centers. Rutgers is a site for the BrUOG-401 study that's looking at the addition potentially of lenalidomide to patients that do not achieve a CR with upfront mosunetuzumab in the first 4 cycles. This is a study that looked at follicular lymphoma and marginal zone lymphoma, so the overall response rates and safety data is all compiled, but again, excellent overall response rates. Very safe.
Interestingly, high rates of grade 1 to 2 rash, a lot of which was associated with mosunetuzumab alone. That's something that we'll need to look at long-term, but again, these were all very manageable toxicities and again with excellent efficacy outcomes, so we'll see how that data matures. I like the idea of potentially adding in treatment if needed as opposed to combining it all upfront. It limits toxicity potentially for patients that have disease biology that is going to be very sensitive to the use of bispecific antibodies.
The last study that we talked about was presented at ASCO. It's arm six of the EPCORE NHL-2 study that looked at the combination of epcoritamab plus R2, which is a very well-established treatment regimen for patients with treated upfront for follicular lymphoma. We saw that patients had excellent responses. Again, 80 to 90% rates of overall response rates with very good progression-free survival at 18 months. This is a great combination. It makes a lot of biologic rationale to combine immunomodulatory agents with a T-cell engaging therapy.
We'll need longer term follow-up to see what the net duration of treatment responses are and the time to next treatment in order to really figure out if these are going to be great treatment strategies for all.
Most of these studies are also being done in a randomized phase 3 fashion currently, so epcoritamab plus R2 is currently being studied in comparison to R2 in a large global randomized phase 3 study, so I'll be excited to see that data to see if we're really being able to move the needle forward for patients with follicular lymphoma for upfront treatment.
Source:
Rhodes J. Updates in frontline treatment of follicular lymphoma . Presented at Lymphoma, Leukemia & Winter Symposium; February 7-9, 2025. Miami, Florida.
