Current state-of-the-art of immunotherapy in follicular lymphoma

The advent of immunotherapy has rapidly changed the treatment landscape of follicular lymphoma (FL). Autologous CD19 chimeric antigen receptor T- cell (CAR-T) products show unprecedented efficacy in third-line FL but substantial rates of cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS). Bispecific antibodies (BSAB) achieve deep and durable responses in heavily pretreated FL patients with less severe CRS and minimal neurological toxicity. BSAB have differing routes of administration, treatment duration and CRS prophylaxis. Checkpoint inhibitors show disappointing response rates in FL. Lenalidomide and tazametostat have modest single agent activity in FL, but synergize with other forms of immunotherapy. CAR-T offers a short duration of therapy with a potential plateau in progression free survival. Major disadvantages include cost, availability, requirement for lymphodepletion and toxicity. BSAB are available 'off the shelf,' have a comparably lower toxicity profile, and are ripe for combination. With both platforms, there are significant infectious risks. There are unanswered questions regarding when to use immunotherapy for FL, impact of disease burden, role of re-treatment and optimal sequencing/combinations. Moving forward, the field will need to develop new prognostic markers, reassess treatment indications, and focus on minimizing toxicity.