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Diffuse large B-cell lymphoma: what clinical progress have we seen in the last 5 years?

James Nolan,J. Kuruvilla

Published 2025 in Expert Opinion on Investigational Drugs

ABSTRACT

ABSTRACT Introduction Diffuse large B-cell lymphoma is the most common subtype of non-Hodgkin lymphoma and has a rapidly evolving treatment landscape. For patients at increased risk of primary treatment failure and those with relapsed/refractory disease, emerging therapeutic classes have significantly improved outcomes. Areas covered This review describes the most important trials evaluating treatment for DLBCL in frontline and the relapsed/refractory setting for both fit patients and patients ineligible for intensive therapy. Particular attention is paid to rational treatment sequencing and selection for CAR-T, bispecific antibodies and molecularly targeted therapies. Expert opinion In modern DLBCL therapy, it is critical to identify individuals at increased risk of primary treatment failure with R-CHOP, who may then be offered the addition of Polatuzumab Vedotin or other targeted therapies in frontline. CAR-T is now a treatment standard in second line for patients with primary refractory or early relapsed disease, with ASCT reserved for eligible patients with later relapse, who may subsequently receive CAR-T in third-line. ASCT ineligible patients also face improved outcomes with CAR-T and enhanced therapies incorporating novel agents. Molecular and genomic tumor profiling is likely in the future to direct optimal treatment for patients by identifying biologically distinct lymphomas sensitive to distinct targeted agents.

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