Prognostic value of BCL2 and TP53 genetic alterations for diffuse large B-cell lymphoma patients treated with R-CHOP

Abstract

Objective: Limited data about the prognostic significance of BCL2 mutations and BCL2 copy number variations in diffuse large B-cell lymphoma (DLBCL) are available. This study aimed to comprehensively describe BCL2 genetic alterations in DLBCL patients, and examine correlation of BCL2 , TP53 and other genetic alterations with outcomes in patients treated with R-CHOP. Methods: Probe capture-based high-resolution sequencing was performed on 191 patients diagnosed with de novo DLBCL. MYC, BCL2, and BCL6 protein expressions were detected by immunohistochemistry. Results: The presence of BCL2 alterations significantly correlated with poor progression-free survival (PFS) (5-year PFS: 13.7% vs. 40.8%; P = 0.003) and overall survival (OS) (5-year OS: 34.0% vs. 70.9%; P = 0.036). Importantly, patients who harbored BCL2 gain/amplifications ( BCL2 GA/AMP ) also had a remarkably inferior 5-year PFS (11.1% vs. 38.3%; P < 0.001) and OS (22.1% vs. 69.6%; P = 0.009). In contrast, neither BCL2 mutations nor BCL2 translocations were significantly prognostic for survival. Multivariable analyses showed that the presence of BCL2 alterations, especially BCL2 GA/AMP , TP53 mutations, and International Prognostic Index (IPI) were significantly associated with inferior PFS and OS. Novel prognostic models for OS were constructed based on 3 risk factors, including BCL2 alterations (Model 1) or BCL2 GA/AMP (Model 2), TP53 mutations, and IPI, to stratify patients into 4 risk groups with different survival outcomes. Conclusions: This study showed that DLBCL patients treated with R-CHOP, BCL2 alterations, especially BCL2 GA/AMP and TP53 mutations were significantly associated with inferior outcomes, which were independent of the IPI. The novel prognostic models we proposed predicted outcomes for DLBCL patients treated with R-CHOP, but further validation of the prognostic models is still warranted.

Efficacy and safety of PD‐1 monoclonal antibody plus rituximab in relapsed/refractory diffuse large B cell lymphoma patients

“…TP53 mutations can be found in 9%-29% of DLBCL patients, which is an independent risk factors related to poor prognosis. [21][22][23][24] In this study, the incidence was as high as 54% (13/24), possibly due to the preference for relapsed and refractory subsets in patient selection.…”

Identification of microtubule-associated biomarkers in diffuse large B-cell lymphoma and prognosis prediction

“…Conventional prognostic evaluation methods, such as the International Prognostic Index (IPI) score and 2-deoxy-2-[F-18]-fluoro-D-glucose (FDG)-PET/CT scan are insufficient to elucidate the clinical diversity of DLBCL ( Zwezerijnen et al, 2021 ). In addition, BCL2 and TP53 mutations are considered prognostic indicators in DLBCL patients ( Qin et al, 2021 ). Nevertheless, the effectiveness of these identified molecular markers has been limited.…”

Enhancement of the International prognostic index with β2-microglobulin, platelet count and red blood cell distribution width: a new prognostic model for diffuse large B-cell lymphoma in the rituximab era

“…During the past decades, the ability of IPI, R-IPI and NCCN-IPI to identify a subgroup of patients with very dismal survival has been proved to be unsatisfactory. Gene expression profiling [29,30], prognostic biomarkers based on immunohistochemistry [31,32], mutational analyses [33][34][35] and novel molecular subtypes [36][37][38] have provided crucially predictive information in DLBCL, allowing for better individual risk prediction.…”