Perspectives on T-cell engaging therapies in relapsed/refractory indolent non-Hodgkin lymphoma

Follicular lymphoma (FL) and marginal zone lymphoma (MZL) are indolent subtypes of non-Hodgkin lymphoma (iNHL) characterized by a relapsing-remitting disease course. A promising novel therapeutic class emerges with T-cell engaging therapies, which include CD19 directed chimeric antigen receptor T-cell (CAR-T) therapy and CD3xCD20 directed bispecific antibodies (BsABs). This review provides a comprehensive evaluation of their efficacy and safety along with logistical considerations in relapsed/refractory (r/r) iNHL. Several pivotal CAR-T trials have presented impressive response rates and durable remissions in r/r FL, while data in MZL is scarce. CAR-T is given as a single infusion, but requires a complex logistical infrastructure. Different BsAbs have shown favorable efficacy with a lower rate of acute toxicities. Off-the-shelve availability favors its usability, although prolonged administration of BsAbs might impose a substantial burden for patients. Long-term infection risk is a concern for both treatments. Clinical studies that directly compare CAR-T and BsAbs are still lacking. Both CAR-T and BsAbs have demonstrated promising efficacy as treatment modalities in iNHL. Decision making for T-cell engaging therapies should be tailored to patient specific factors and availability. Maturation of follow-up data will further guide evidence-based treatment choices in FL and MZL.