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T-cell–redirecting immunotherapies, including CAR-T therapy and bispecific antibodies, have reshaped treatment strategies. CAR-T approaches such as brexu-cel and liso-cel provide high response rates and durable remissions, but require bridging care, face logistical constraints, and can cause severe toxicities like CRS and ICANS. Bispecific antibodies targeting CD20 and CD3 offer off-the-shelf repeat dosing with generally manageable toxicity. The review details CRS mitigation with step-up dosing, corticosteroids, and anti-IL6 therapy, highlights hematologic risks and infection monitoring, and outlines evidence supporting rational sequencing and combination regimens, including use as bridge to CAR-T or consolidation after BisAb response, to improve long-term outcomes.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/t-cellredirecting-immunotherapies-in-relapsedrefractory-mantle-cell-lymphoma-current-evidence-sequencing-and-future-directions/458496/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/t-cellredirecting-immunotherapies-in-relapsedrefractory-mantle-cell-lymphoma-current-evidence-sequencing-and-future-directions/458496.png","ImageObject",300,407,{"name":92,"@type":93},"Đào","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is relapsed/refractory mantle cell lymphoma difficult to treat?","Question",{"text":112,"@type":113},"It is challenging particularly in patients with high-risk features or prior exposure to Bruton's tyrosine kinase inhibitors. Disease biology and prognosis vary widely, contributing to inconsistent outcomes.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What benefits and limitations are associated with CAR-T therapy in this setting?",{"text":117,"@type":113},"CAR-T therapies such as brexu-cel and liso-cel can induce high overall response rates and durable remissions, even after heavy pretreatment. Limitations include logistical constraints, need for bridging therapy, and risks of severe toxicities like CRS and ICANS.",{"name":119,"@type":110,"acceptedAnswer":120},"How do bispecific antibodies fit into treatment and what toxicities require attention?",{"text":121,"@type":113},"Bispecific antibodies targeting CD20 and CD3 provide off-the-shelf, repeatable immunotherapy, often suitable for outpatient use, with generally manageable toxicities. 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The advent ofT-cell–redirecting immunotherapies, including chimeric antigen receptor T-cell (CAR-T) therapy and bispecific antibodies (BsAbs), has transformed the treatment landscape. CAR-T therapies, such as brexu-cel and liso-cel, induce high overall response rates and durable remissions, even in heavily pretreated or BTKi-refractory patients. However, CAR-T administration is limited by logistical constraints, the need for bridging therapy, and the risk of severe toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) . BsAbs, targeting CD20 and CD3, offer an off-the-shelf, repeatable immunotherapeutic option suitable for outpatient use, with generally manageable toxicities. Step-up dosing, corticosteroids, and anti-IL6 therapy mitigate CRS, while hematologic toxicity and infections require vigilant monitoring. Clinical data indicate that BsAbs are active in both CAR-T–naïve and post-CAR-T settings, providing disease control in patients ineligible for immediate CAR-T therapy. Emerging evidence supports rational sequencing and combinatorial strategies to optimize outcomes. BsAbs may be employed as a bridge to CAR-T, or CAR-T may be used to consolidate BsAb-induced remissions. Combination regimens, including CAR-T or BsAbs with BTK inhibitors or other targeted agents, are under investigation to enhance the depth and durability of response. In conclusion, CAR-T and BsAbs are complementary modalities in R/R MCL. Individualized therapeutic sequencing and rational combinations, tailored to disease biology and patient characteristics, represent the next frontier for improving long-term outcomes in this historically high-risk population.  \n1 | Introduction  \nMantle cell lymphoma (MCL) is a rare and biologically heterogeneous subtype of non-Hodgkin lymphoma (NHL) . Its clinical spectrum ranges from indolent forms associated with long-term  \nsurvival to highly aggressive variants with dismal outcomes. At diagnosis, the majority of patients present with advanced-stage disease and frequent extranodal involvement, including bone marrow (53%–82%), peripheral blood (≈50%), liver (≈25%), and gastrointestinal tract (20%–60%) . The molecular hallmark of  \nThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.  \n© 2025 The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.  \nEuropean Journal of Haematology, 2026; 116:129–141 129  \n[https://doi.org/10.1111/ejh.70063](https://doi.org/10.1111/ejh.70063)  \nMCL is the CCND1 translocation, result","cbCaiqNFHTqkAKzN","https://ap.wps.com/l/cbCaiqNFHTqkAKzN","pdf",1160440,13,"English","# Abstract\n# Introduction\n## Disease background and biology\n## Prognostic stratification and high-risk features\n# Therapeutic landscape of T-cell–redirecting immunotherapies\n## CAR-T therapy overview\n## Bispecific antibodies overview\n## Toxicity mitigation and monitoring\n# Sequencing strategies and future directions","[{\"question\":\"Why is relapsed/refractory mantle cell lymphoma difficult to treat?\",\"answer\":\"It is challenging particularly in patients with high-risk features or prior exposure to Bruton's tyrosine kinase inhibitors. Disease biology and prognosis vary widely, contributing to inconsistent outcomes.\"},{\"question\":\"What benefits and limitations are associated with CAR-T therapy in this setting?\",\"answer\":\"CAR-T therapies such as brexu-cel and liso-cel can induce high overall response rates and durable remissions, even after heavy pretreatment. Limitations include logistical constraints, need for bridging therapy, and risks of severe toxicities like CRS and ICANS.\"},{\"question\":\"How do bispecific antibodies fit into treatment and what toxicities require attention?\",\"answer\":\"Bispecific antibodies targeting CD20 and CD3 provide off-the-shelf, repeatable immunotherapy, often suitable for outpatient use, with generally manageable toxicities. CRS mitigation may involve step-up dosing, corticosteroids, and anti-IL6 therapy, while hematologic toxicity and infections require vigilant monitoring.\"}]","T-Cell–Redirecting Immunotherapies in Relapsed/Refractory Mantle Cell Lymphoma - Current Evidence, Sequencing, and Future Directions | PDF",1790753424,33]