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Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, and despite advances in frontline therapies such as rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate (Oncovin), and prednisone, approximately 30%-40% of patients develop relapsed or refractory (rel/ref) disease. This subgroup has historically faced poor prognoses with limited treatment options, prompting the development of novel immunotherapeutic strategies. Chimeric antigen receptor T-cell (CAR T) therapy and bispecific antibodies (BsAbs) have emerged as transformative approaches in this setting.

This narrative review compares these therapies across multiple domains, including mechanisms of action, clinical efficacy, safety profiles, logistics, cost, and accessibility.

CAR T therapies have demonstrated durable complete response rates (40%-60%) and extended progression-free survival (median 11-12.5 months), but they are limited by complex manufacturing, high cost, and potentially severe toxicities. In contrast, BsAbs offer immediate, off-the-shelf availability, with promising efficacy and a more favorable safety profile that enables outpatient administration, although long-term durability remains under investigation.

This review provides clinicians with a comprehensive comparison to support evidence-based treatment selection in rel/ref DLBCL.