Moving T-Cell Therapies into the Standard of Care for Patients with Relapsed or Refractory Follicular Lymphoma: A Review.

Patients with follicular lymphoma, an indolent form of non-Hodgkin lymphoma, typically experience multiple relapses over their disease course. Periods of remission become progressively shorter with worse clinical outcomes after each subsequent line of therapy. Currently, no clear standard of care/preferred treatment approach exists for patients with relapsed or refractory follicular lymphoma. As novel agents continue to emerge for treatment in the third-line setting, guidance is needed for selecting the most appropriate therapy for each patient. Several classes of targeted therapeutic agents, including monoclonal antibodies, phosphoinositide 3-kinase inhibitors, enhancer of zeste homolog 2 inhibitors, chimeric antigen receptor (CAR) T-cell therapies, and bispecific antibodies, have been approved by regulatory authorities based on clinical benefit in patients with relapsed or refractory follicular lymphoma. Additionally, antibody-drug conjugates and other immunocellular therapies are being evaluated in this setting. Effective integration of CAR-T cell therapy into the treatment paradigm after two or more prior therapies requires appropriate patient selection based on transformation status following a rebiopsy; a risk evaluation based on age, fitness, and remission length; and eligibility for CAR-T cell therapy. Consideration of important logistical factors (e.g., proximity to the treatment center and caregiver support during key periods of CAR-T cell therapy) is also critical. Overall, an individualized treatment plan that considers patient-related factors (e.g., age, disease status, tumor burden, comorbidities) and prior treatment types is recommended for patients with relapsed or refractory follicular lymphoma. Future analyses of real-world data and a better understanding of mechanisms of relapse are needed to further refine patient selection and identify optimal sequencing of therapies in this setting.