Latest Follicular Lymphoma Research from ASH 2025

At the 2025 American Society of Hematology’s Annual Meeting, researchers testing new and existing treatments for blood cancers like follicular lymphoma gathered to present their results. 

In this article, discover some of the latest research on how new treatments compare with older approaches and what options may be available at different points in follicular lymphoma care. 

A chemotherapy-free combination for newly diagnosed follicular lymphoma

The phase 2 MITHIC-FL2 study looked at mosunetuzumab (Lunsumio, Genentech), a bispecific antibody that helps immune cells recognize lymphoma cells, combined with zanubrutinib (Brukinsa, BeOne), a BTK inhibitor that blocks signals lymphoma cells use to grow. The study enrolled people with newly diagnosed, high-burden follicular lymphoma who needed treatment.

Early results showed most participants responded, with 74% achieving a complete response, meaning no active lymphoma was seen on scans. Side effects were mostly mild to moderate, such as injection-site reactions and fatigue, and treatment was given in an outpatient setting. For patients, this matters because it suggests a possible first treatment option that avoids chemotherapy while still leading to deep responses.

Read this abstract: Combined mosunetuzumab and zanubrutinib for the treatment of patients with newly diagnosed high-burden follicular lymphoma: First results of the multicenter phase 2 mithic-FL2 trial

Rituximab plus epcoritamab as a first treatment option

Another phase 2 study tested rituximab (Rituxan, Genentech/Biogen) with epcoritamab (Epkinly, Genmab/AbbVie), a bispecific antibody. Rituximab was given before epcoritamab to lower patients’ lymphoma burden. 

Nearly all participants responded, and 91% reached a complete metabolic response on PET-CT scans. Cytokine release syndrome, an immune-related side effect, was mostly mild and occurred less often with adjusted dosing. These findings are important because they show that carefully planned combinations may reduce side effects while keeping response rates high.

Read this abstract: Rituximab and epcoritamab as first-line therapy for patients with high-tumor burden follicular lymphoma: Results of a multicenter phase II trial

Long-term results with epcoritamab plus R² as a first treatment 

The phase 1b/2 EPCORE NHL-2 study followed participants with follicular lymphoma who received epcoritamab combined with rituximab and lenalidomide, often called R², as a first therapy. After about three years of follow-up, most patients remained in remission, and many were MRD-negative. 

For people with follicular lymphoma, longer follow-up is reassuring. It shows that responses can last several years with fixed-duration treatment. 

Epcoritamab with R² was recently FDA-approved as a second follicular lymphoma treatment. Learn more here. 

Read this abstract: Epcoritamab with rituximab + lenalidomide (R2) and epcoritamab maintenance deliver deep and durable remissions in previously untreated (1L) follicular lymphoma (FL): 3-year outcomes from epcore NHL-2 arms 6 and 7

Three-year follow-up with CAR T-cell therapy liso-cel

The phase 2 TRANSCEND FL trial followed people with follicular lymphoma who received liso-cel (Breyanzi, Juno Therapeutics/BMS), a CAR T-cell therapy, after multiple prior treatments. CAR-T uses a person’s own immune cells, modified to better recognize lymphoma cells. 

At three years, most participants were still alive, and 93% of those who achieved a complete response remained in remission. Serious side effects, such as low blood counts, improved over time. For patients considering CAR-T, this shows that a single infusion can lead to long-lasting benefits for some people.

Read this abstract: Three-Year Efficacy and Longitudinal Safety of Lisocabtagene Maraleucel (liso-cel) in Patients With Third-Line or Later (3L+) Follicular Lymphoma (FL) From TRANSCEND FL

Five-year outcomes with CAR-T tisa-cel

The phase 2 ELARA study provided more than five years of follow-up for tisa-cel (Kymriah, Novartis), another CAR T-cell therapy for follicular lymphoma. About half of the participants were still progression-free at five years, including many with high-risk features.

These results can help patients understand how durable responses may be with CAR-T, even several years after treatment. 

Read this abstract: Clinical outcomes of tisagenlecleucel in patients with relapsed/refractory follicular lymphoma (r/r FL): Phase 2 ELARA 5-year update

Summary

Together, these studies show continued progress toward chemotherapy-free and time-limited treatments, with some options offering long-lasting responses. Each approach has different benefits and side effects, so discussing these results with a follicular lymphoma specialist can help you understand how new research may fit into your care.

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Sources: 

• Combined mosunetuzumab and zanubrutinib for the treatment of patients with newly diagnosed high-burden follicular lymphoma: First results of the multicenter phase 2 mithic-FL2 trial
• Rituximab and epcoritamab as first-line therapy for patients with high-tumor burden follicular lymphoma: Results of a multicenter phase II trial
• Epcoritamab with rituximab + lenalidomide (R2) and epcoritamab maintenance deliver deep and durable remissions in previously untreated (1L) follicular lymphoma (FL): 3-year outcomes from epcore NHL-2 arms 6 and 7
• Three-Year Efficacy and Longitudinal Safety of Lisocabtagene Maraleucel (liso-cel) in Patients With Third-Line or Later (3L+) Follicular Lymphoma (FL) From TRANSCEND FL
• Clinical outcomes of tisagenlecleucel in patients with relapsed/refractory follicular lymphoma (r/r FL): Phase 2 ELARA 5-year update