Treatment of relapsed and refractory follicular lymphoma: which treatment for which patient for which line of therapy?

ABSTRACT: Recent advances have transformed the treatment landscape for relapsed and refractory follicular lymphoma. Although chemotherapy has long served as the backbone of treatment, the availability of novel targeted, immunomodulatory, and immunotherapeutic approaches is challenging its relevance. These approaches have focused on targeting epigenetic regulators, components of the B-cell receptor or its downstream intracellular pathways and the follicular lymphoma tumor microenvironment. The recent development of bispecific antibodies and chimeric antigen receptor T-cell therapies, which target both tumor-associated and host-specific antigens, has enabled a redirection of the immune system, enhancing the innate antitumor immune response. Rational combinations of these strategies are actively being evaluated in the relapsed and refractory setting and will inevitably move forward into earlier lines of treatment. The success of these approaches has led to numerous and parallel options for patients and clinicians. The emerging challenge now lies in how best to approach each individual patient with relapsed or refractory follicular lymphoma, addressing complex decision-making that considers a patient's previous treatment history, goals of care, clinical and biological characteristics of recurrence, and personal preferences. Understanding the implications of refractory and transformed disease, as well as the timing and biology of relapse will be critical to support a more personalized treatment approach in the modern era.