Influence of <i>TP53</i> Mutation on Survival of Diffuse Large B-Cell Lymphoma in the CAR T-Cell Era
Refractory/relapsed diffuse large B-cell lymphoma (DLBCL) is associated with poor outcome. The clinical behavior and genetic landscape of DLBCL is heterogeneous and still not fully understood. <i>TP53</i> mutations in DLBCL have been identified as markers of poor prognosis and are often...
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| Autores principales: | , , , , , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/0714d84a987446bcba6ed96dac848f51 |
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| Sumario: | Refractory/relapsed diffuse large B-cell lymphoma (DLBCL) is associated with poor outcome. The clinical behavior and genetic landscape of DLBCL is heterogeneous and still not fully understood. <i>TP53</i> mutations in DLBCL have been identified as markers of poor prognosis and are often associated with therapeutic resistance. Chimeric antigen receptor T-cell therapy is an innovative therapeutic concept and represents a game-changing therapeutic option by supporting the patient’s own immune system to kill the tumor cells. We investigated the impact of <i>TP53</i> mutations on the overall survival of refractory/relapsed DLBCL patients treated with comparable numbers of therapy lines. The minimum number of therapy lines was 2 (median 4), including either anti-CD19 CAR T-cell therapy or conventional salvage therapy. A total of 170 patients with DLBCL and high-grade B-cell lymphoma with <i>MYC, BCL2,</i> and/or <i>BCL6</i> rearrangements (DHL/THL), diagnosed and treated in our hospital between 2000 and 2021, were included. Twenty-nine of them received CAR T-cell therapy. <i>TP53</i> mutations were found in 10/29 (35%) and 31/141 (22%) of patients in the CAR T-cell and conventional groups, respectively. Among the 141 patients not treated with CAR T cells, <i>TP53</i> mutation was an independent prognostic factor for overall survival (OS) (median 12 months with <i>TP53</i> vs. not reached without <i>TP53</i> mutation, <i>p</i> < 0.005), but in the CAR T cell treated group, this significance could not be shown (median OS 30 vs. 120 months, <i>p</i> = 0.263). The findings from this monocentric retrospective study indicate that <i>TP53</i> mutation status does not seem to affect outcomes in DLBCL patients treated with CAR T-cell therapy. Detailed evaluation in large cohorts is warranted. |
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