Although novel agents such as polatuzumab and lenalidomide may have shown promising results in the treatment of refractory diffuse large B-cell lymphoma (DLBCL), survival is still poor among patients with disease progression or relapse after therapy with CD19-directed chimeric antigen receptor (CAR) T-cell therapy, according to a recently published study in the journal Leukemia.

CAR T-cell therapy has markedly improved survival rates in patients with DLBCL refractory to standard anthracycline-based chemotherapy regimens, achieving a response rate close to 70% in this subgroup of patients, Ana Alarcon Tomas, of the Hospital Universitario Gregorio Marañón, in Madrid, Spain, and colleagues noted. Unfortunately, the prognosis of patients that do not respond to CAR T-cell therapy is still poor; furthermore, the relapse rate of patients with initial response reaches 60%, the researchers added.

The therapeutic arsenal for patients with double-resistant DLBCL has grown in recent years, with monoclonal antibodies, such as polatuzumab and loncastuximab, receiving US Food and Drug Administration approval for patients with at least 2 failed therapies, and other therapeutic alternatives such as lenalidomide showing promise as well, the study authors noted.

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So far, studies regarding treatment for patients with relapse after CAR T-cell therapy have small sample sizes and heterogeneous treatment strategies. Therefore, the authors aimed to report the outcomes of patients with disease progression or relapse after CAR T-cell therapy through a retrospective observational research study including over 300 patients, representing the largest study of its kind to date. 

Of the 305 patients included in the study, approximately 60% experienced relapse or disease progression during the period of the study. The median overall survival in patients with relapse was 8 months.

Approximately 70% of patients with treatment failure received the third line of treatment, with polatuzumab, standard chemotherapy, and lenalidomide-based treatments being the most common.

None of the patients receiving conventional chemotherapy after treatment failure had a complete response, while approximately 30% of the patients that received polatuzumab or lenalidomide-based therapies had a complete response.

“In this largest analysis to date of patients who progressed or relapsed after CD19-CAR-T, survival is poor, though novel agents such as polatuzumab and lenalidomide may hold promise,” the authors concluded.


Alarcon Tomas A, Fein J, Fried S, et al. Outcomes of first therapy after CD19-CAR-T treatment failure in large B-cell lymphoma. Leukemia. Published online November 5, 2022. doi:10.1038/s41375-022-01739-2