Emerging Treatments Improve Outcomes for Patients With Relapsed/Refractory Follicular Lymphoma

Recent advancements in bispecific antibodies (BsAbs) and chimeric antigen receptor (CAR) T-cell therapies are revolutionizing the treatment landscape for patients with relapsed or refractory follicular lymphoma (RR-FL), offering new hope for those who have exhausted traditional treatment options.

Follicular lymphoma accounts for 20% to 30% of non-Hodgkin lymphoma (NHL) cases and is often diagnosed at an advanced stage. While initial treatment options, such as rituximab monotherapy or chemoimmunotherapy, offer prolonged progression-free survival (PFS), many patients experience disease relapse or become refractory to standard therapies. Research into immune-based therapies, including BsAbs and CAR T-cell therapies, have provided exciting advancements for RR-FL treatment.

These innovative therapies have demonstrated impressive efficacy in clinical trials, with high overall response rates (ORRs) and durable remissions. Mosunetuzumab, a CD20 × CD3 BsAb, has shown an ORR of approximately 80%, with a notable complete remission (CR) rate of 60% in heavily pretreated patients with RR-FL. Similarly, glofitamab and epcoritamab have exhibited promising results, with ORRs ranging from 81% to 100% in various studies.

CAR T-cell therapies, including axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabtagene maraleucel (liso-cel), have also demonstrated remarkable efficacy. In the ZUMA-5 study, axi-cel achieved a 95% ORR, with 79% complete remissions in patients with RR-FL. Tisa-cel and liso-cel have shown similarly impressive results, with high response rates and durable remissions.

While these therapies offer significant benefits, they are not without challenges. Both BsAbs and CAR T-cell therapies can cause side effects such as cytokine release syndrome (CRS) and neurotoxicity. However, management strategies—such as step-up dosing and prophylactic measures—have been developed to mitigate these risks.

Cost-effectiveness analyses have yielded mixed results, with some studies suggesting that CAR T-cell therapies may be more cost-effective in the long term, whereas others indicate that BsAbs, such as mosunetuzumab, may offer a more favorable economic profile. These conflicting findings highlight the need for further research and real-world evidence to inform treatment decisions.

As the field continues to evolve, ongoing studies are exploring the potential of these therapies in earlier lines of treatment and in combination with other agents. The future looks promising for patients with RR-FL, with these innovative approaches offering new possibilities for improved outcomes and quality of life.

“Until recently, a definitive standard of care for RR-FL had not been established, as evidenced by the findings of the SCHOLAR-5 trial,” concluded the study authors. “However, the advent of CAR-T therapy and BsAbs has shown significant efficacy in the setting of this hard-to-treat population.”

Reference

Morabito F, Martino EA, Nizzoli ME, et al. Comparative analysis of bispecific antibodies and CAR T-cell therapy in follicular lymphoma. Eur J Haematol. 2025;114(1):4-16. doi:10.1111/ejh.14335