Towards a chemo-free approach for follicular lymphoma

The therapeutic landscape of follicular lymphoma (FL) is undergoing a transformative shift driven by the advent of novel chemo-free strategies that challenge the traditional chemo-oriented paradigms; this shift offers promising alternatives for both newly diagnosed and relapsed or refractory (RR) patients. Available data support a full chemo-free approach starting from second-line therapy, with rituximab-lenalidomide (R2) or tafasitamab-R2, whereas bispecific antibodies (bsAbs), Bruton's tyrosine kinase (BTK) inhibitors and chimeric antigen receptor (CAR) T-cell therapies are available options after second relapse. In the near future, bsAbs, mainly in combination with lenalidomide, will likely be employed as first- or second-line therapy, potentially fully replacing immunochemotherapy, whereas CAR T-cell therapy will play a role in selected high-risk patients. Given the different toxicity profiles of chemo-free options, refined prognostic scores are awaited so as to properly allocate patients to the most appropriate therapy with the best trade-off between efficacy and safety.