A SWOT-Consensus for CAR-T in Follicular Lymphoma: Fine Tuning of Patient Journey and Selection

Abstract

Over the past 2 decades, advancements in follicular lymphoma (FL) treatment, particularly with anti-CD20 antibodies, have significantly improved patient survival. However, a subset of FL patients experiences early relapse and progression within 24 months (POD24) after first line treatment, which is a sign of poor prognosis. Current guidelines recommend various second-line treatments, but there is no consensus on an optimal treatment sequence for relapsed/refractory (r/r) FL. Moreover, despite available treatments, reduced survival after second-line therapies and diminishing responses with each relapse highlight the unmet need for more effective options. Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a promising treatment for r/r FL beyond 2^nd line therapy, with three FDA/EMA-approved therapies (axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel) showing high efficacy and manageable side effects. However, challenges remain in determining which patients will benefit most from CAR-T, especially given its high cost, safety concerns, and logistical barriers. A consensus study was conducted to guide CAR-T patient selection and treatment sequencing for patients in 3rd line or beyond. Key findings suggest that younger patients, those with high disease burden or poor first-line responses, should be prioritized for CAR-T. Additionally, CAR-T is recommended as a third-line option for patients with POD24, double refractoriness (failure to respond to two subsequent lines of immunochemotherapy), or early autologous stem cell transplant failure. The study underscores the importance of early assessment of treatment response, careful second-line therapy selection, and patient adherence to ensure optimal outcomes. The results, based on expert consensus, support CAR-T therapy as a viable option for r/r FL patients, offering hope for durable remissions in this challenging cohort.