Emerging Therapies Reshaping Follicular Lymphoma Treatment

The future treatment landscape for follicular lymphoma is being rapidly shaped by several promising agents and novel combinations focused on escalating targeted immunotherapy. This progress reflects a broader paradigm shift in oncology toward highly precise, multi-pronged strategies. Researchers are consistently exploring ways to leverage the body's own immune system while enhancing delivery and efficacy. The goal remains achieving deeper, more durable responses across different patient populations.

One key emerging area involves dual-targeting bispecific antibodies, such as an investigational CD19/CD3 bispecific that is showing significant early activity in follicular lymphoma. This strategy aims to bridge the patient’s T cells to the CD19-expressing lymphoma cells. A second, more aggressive approach draws from the large B-cell lymphoma playbook, where combining a CD20-directed bispecific antibody with other agents such as loncastuximab is demonstrating results potentially comparable to CAR T-cell therapy in a small, yet impactful, early study. This suggests a future where dual CD19/CD20 targeting, possibly using combination bispecifics or even bispecific-bispecific drug combinations, could become standard.

Bispecific antibodies are poised to rapidly move into earlier follicular lymphoma treatment, likely within the next 2 to 3 years. This shift will then impact second-line sequencing, requiring clinicians to rethink therapy choices, especially after CD20-directed initial treatments.

The second-line treatment armamentarium is also shifting based on promising phase 2 and upcoming phase 3 data around triple combination therapy, particularly in terms of progression-free survival. The rapid success of potent combinations is likely to spur clinicians to rethink the optimal sequencing of therapies, potentially positioning these combinations earlier and reserving CAR T-cell therapy for later lines.