Beyond Chemoimmunotherapy: Emerging Cellular and Targeted Therapies in Transformed Follicular Lymphoma: A Scoping Review

IntroductionTransformed follicular lymphoma (t-FL) is an aggressive lymphoma with limited prospective evidence to guide treatment, particularly in the relapsed setting. We summarized the current evidence on emerging cellular and targeted therapies that extend beyond conventional chemoimmunotherapy.MethodsThis scoping review was conducted in accordance with the PRISMA extension for Scoping Reviews (PRISMA-ScR) and structured using the Population-Concept-Context (PCC) framework. Adults with histologically confirmed or strongly suspected t-FL were the population of interest. Findings were synthesized narratively.ResultsSeventeen studies met inclusion criteria across three therapeutic categories: CAR-T therapy (7 interventional trials, n = 130 t-FL patients in reported subsets), CD20×CD3 bispecific antibodies (BsAbs; n = 61 t-FL patients with extractable outcomes), and selinexor (n = 31 t-FL patients); together encompassing approximately 222 t-FL patients across primary interventional cohorts with extractable outcomes. CAR-T products achieved overall response rates (ORR) of 52-83% and complete response (CR) rates of 40-58%; randomized second-line trials favored axicabtagene ciloleucel and lisocabtagene maraleucel over standard care. In real-world CAR-T series, ORR ranged from 82-92% and CR rates from 64-67% across registry cohorts. BsAbs were active in heavily pretreated disease (epcoritamab ORR 50%/CR 44%; glofitamab ORR 55%/CR 35%), with predominantly low-grade cytokine release syndrome. Selinexor showed more modest efficacy (ORR 39%/CR 16%) but durable benefit in complete responders.ConclusionsCurrent evidence supports a stepwise treatment framework: DLBCL-like induction at transformation, autologous stem-cell transplant in fit, chemosensitive responders, CAR-T as the preferred option at first relapse, BsAbs after CAR-T or when cellular therapy is not feasible, and selinexor in later-lines of therapy. Additional prospective t-FL-inclusive trials are needed to refine treatment selection and biomarker-guided sequencing.