Chimeric antigen receptor T-cells (CAR-T) in patients with extranodal diffuse large B cell lymphoma (DLBCL) appears to have a similar impact on long and short-term outcomes as in patients with nodal disease; however, patients with more than 3 extranodal sites appear to have worst outcomes, according to a recently published study in the European Journal of Hematology.

Since its release in 2017, CAR-T cell therapy has become a popular therapeutic alternative for DLBCL; therefore, there is currently a high interest in investigating factors impacting response to treatment as well as its safety profile in different patient populations. In particular, the response of extranodal DLBCL is poorly documented.

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“In this multicenter study, we provide a comprehensive description of the response and associated toxicity of diverse extranodal organs to commercially available CAR-T cells and compared to patients with nodal disease,” the authors wrote.

The study included over 120 patients with DLBCL receiving CAR-T cell therapy from 4 different centers in Israel between 2019 and 2021.

At the moment of lymphodepletion therapy before CAR-T cell therapy, 57% of the included population had extranodal disease, and approximately 10% had affectation of more than 2 extranodal sites.

The authors noted that patients with gastrointestinal, urinary, and pharyngeal involvement had a particularly poor response compared to those with pulmonary and breast involvement.

Results showed that there was no statistically significant difference in overall response after 1 month of treatment among patients with extranodal and nodal disease. After a median follow up of approximately 8 months, the survival rate of the whole population was 68%. There was no significant difference in overall survival or progression-free survival among both groups.

Nonetheless, subgroup analysis revealed that patients with an affectation of more than 2 extranodal sites had worse progression-free survival and overall survival than those with less than 2 extranodal sites. In conclusion, the survival of patients with extranodal involvement appears similar to patients with nodal disease at lymphodepletion prior to CAR-T cells. Three or more extranodal sites and high lactate dehydrogenase were associated with reduced survival and very poor outcomes.

“Although there was a slightly higher rate of overall cytokine release syndrome(CRS) in patients with extranodal disease, it did not reach statistical significance. The most commonly affected organs in both groups were bone marrow and liver,” the authors concluded.


Katz OB, Perry C, Greenzaid SG, et al. Response rates of extra‐nodal diffuse large B cell lymphoma to anti cd19‐car T cells ‐ a real word retrospective multi‐center study. European Journal of Haematology. Published online March 25, 2023. doi:10.1111/ejh.13968