Evaluating the Role of CAR-T Cell Therapy in the Context of Current Therapy Options for Patients With Relapsed or Refractory Follicular Lymphoma.

Follicular lymphoma (FL), the most common subtype of indolent non-Hodgkin lymphoma, exhibits significant clinical heterogeneity, with some patients enjoying durable periods of active surveillance and others having a more aggressive course characterized by frequent relapses and sometimes transformation to high-grade lymphoma. Consequently, treatment is highly individualized. Currently, there is no standard regimen established for patients with relapsed or refractory (r/r) FL. The only established curative-intent treatment for r/r FL is hematopoietic stem cell transplantation, but its application is limited by toxicity. Currently there is a need for effective therapies that could provide longer disease control without significant increase in toxicities. Agents in development include chimeric antigen receptor (CAR)-T cell therapy, monoclonal anti-cluster of differentiation (CD)20 antibodies, kinase inhibitors, enhancer of zeste homolog 2 inhibitors, cereblon E3 ligase modulatory drugs, and bispecific antibodies. Some of these therapies have already been approved for use in patients with r/r FL with ≥2 previous lines of therapy, but sequencing and standardization of treatment are still lacking. CAR-T cell therapy has been shown to have durable efficacy with manageable adverse events, such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. Bispecific antibodies have been shown to demonstrate a good overall response rate but their long-term efficacy has not been established. Several trials on targeted therapies have also shown promising results. Clinical trials using a combination of these therapeutic agents are still limited, as are real-world studies in patients with r/r FL given cellular therapy. Despite this expansion of the treatment landscape among patients with third-line r/r FL, there still exists an unmet need for a standardized, stepwise approach in the treatment of this population. Herein we review the efficacy and safety of CAR-T cell therapy and non-CAR-T cell therapy in the management of r/r FL.