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How Immunotherapy Is Reshaping DLBCL Care
Diffuse large B-cell lymphoma (DLBCL) remains one of the most common and clinically diverse forms of non-Hodgkin lymphoma. Although frontline chemoimmunotherapy can produce durable remission for many patients, approximately 30% to 40% will experience relapsed or refractory disease. This ongoing challenge has accelerated the development of immunotherapies designed to engage the immune system or more precisely target malignant B cells, substantially expanding the therapeutic landscape for patients whose disease does not respond adequately to initial treatment.
CAR T-cell therapy has become an important part of this changing landscape, particularly in relapsed or refractory disease. By engineering a patient's T cells to recognize tumor-associated antigens such as CD19, CAR T-cell therapies can generate potent antitumor responses in patients who have received previous treatment. Clinical studies have demonstrated durable remissions in subsets of patients, and some CAR T-cell therapies have moved earlier in the DLBCL treatment pathway. However, antigen loss, impaired T-cell persistence, T-cell exhaustion, and an immunosuppressive tumor microenvironment can contribute to resistance and disease progression.
Bispecific antibodies offer another approach by simultaneously engaging an antigen on malignant B cells and CD3 on T cells, bringing the two cells together to promote tumor-cell killing. CD20xCD3 bispecific antibodies have demonstrated activity in heavily pretreated relapsed or refractory DLBCL, including patients previously exposed to other advanced therapies. Epcoritamab, a subcutaneously administered CD20xCD3 bispecific antibody, has demonstrated responses in relapsed or refractory large B-cell lymphoma after multiple prior lines of therapy, illustrating the growing role of this therapeutic class in later-line disease.
The immunotherapy landscape also extends beyond CAR T-cell therapy and bispecific antibodies. Antibody-drug conjugates combine targeted antibodies with cytotoxic payloads, allowing treatment to deliver a cancer-killing agent more directly to cells expressing a particular antigen. Monoclonal antibodies and immune checkpoint inhibitors represent additional strategies under investigation, although activity varies substantially among approaches and clinical settings. Together, these modalities illustrate how DLBCL treatment is becoming increasingly diverse rather than relying on a single therapeutic strategy.
As more immunotherapies become available, an important challenge will be determining how they can be used most effectively across the DLBCL treatment course. Resistance mechanisms, differences in patient response, molecular heterogeneity, toxicity, and access to advanced testing can all influence treatment decisions. Continued research into biomarkers, combination strategies, molecular profiling, and treatment sequencing may ultimately help clinicians better identify which patients are most likely to benefit from specific immunotherapeutic approaches and support a more individualized approach to DLBCL care.