Molecular profiling of Chinese <scp>R‐CHOP</scp> treated <scp>DLBCL</scp> patients: Identifying a high‐risk subgroup

Jiang, Shiyu; Qin, Yan; Jiang, Hong-Chen; Liu, Biao; Shi, Jian-Quan; Fang, Meng; Liu, Peng; Yang, Jianliang; Yang, Sheng; He, Xiaohong; Zhou, Shengyu; Gui, Lin; Líu, Hao; Lin, Jing; Han‐Zhang, Han; Shi, Yuankai

doi:10.1002/ijc.33049

“…TP53 mutations have been shown to be significantly associated with poor overall survival in DLBCL [ 38 , 39 ]. Clipson A et al [ 40 ] also found the significant association of TP53 mutation with poor overall survival in DLBCL with MYC translocation.…”

Section: Discussionmentioning

confidence: 99%

Primary breast double-hit lymphoma management and outcomes: a real-world multicentre experience

Zhang

¹

,

Zhang

²

,

Fei

³

et al. 2021

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Background Primary breast double-hit lymphoma (PB-DHL) is a rare, highly aggressive malignancy that poses challenges regarding accurate diagnosis and selecting optimal treatment regimens. Methods We retrospectively reviewed 48 cases of patients diagnosed with PB-DHL in six academic centres between June 2014 and June 2020 in China. Study-specific data were recorded, including treatment options, therapeutic evaluation, prognostic factors and relapse patterns, and the overall survival (OS) and progression-free survival (PFS) were evaluated. Results In total, 48 patients were enrolled, with 14 patients treated with DA-EPOCH-R/MA (rituximab, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, alternating with high-dose methotrexate and cytarabine), 18 patients treated with DA-EPOCH-R (rituximab, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin), and 16 patients treated with R-HyperCVAD (rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, alternating with cytarabine plus methotrexate). The overall 5-year OS and PFS rates were 41.7% (95% confidence interval [CI], 27.6–56.8%) and 37.5% (95% CI, 24.0–52.6%), respectively. Of the three treatment regimens, the 5-year OS was higher in DA-EPOCH-R/MA group than in the DA-EPOCH-R or R-HyperCVAD subgroups (57.1% vs. 38.9% vs. 31.3%; P = 0.016), as was the 5-year PFS (50.0% vs. 38.9% vs. 25.0%; P = 0.035). Autologous stem cell transplantation (ASCT) prolonged the OS and PFS compared with non-ASCT patients (5-year OS: 72.2% vs. 23.3%; P < 0.001; 5-year PFS: 72.2% vs. 16.7 %, P < 0.001). Multivariate analysis identified tumour size, risk stratification, treatment with DA-EPOCH-R/MA, breast irradiation, and ASCT as significant prognostic factors. Conclusions DA-EPOCH-R/MA is a promising regimen for PB-DHL, and breast irradiation yields complementary benefits for prognosis. ASCT significantly decreased disease relapse, providing a potential curative PB-DHL intervention and justifying ASCT as first-line therapy for young patients. More effective treatment strategies for PB-DHL patients remain encouraging.

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“…Driven by the purpose of identifying genetic high-risk subtypes, most patients in that series presented with advanced-stage and high-risk disease according to the revised international prognostic index (R-IPI; part of the study has been published). 25 Retrospectively selected from that cohort, patients harboring TP53 mutations were enrolled in the present study. Clinical data were collected and analyzed: sex, age, Ann Arbor stage, Eastern Cooperative Oncology Group performance status, extranodal involvement, B symptoms, lactate dehydrogenase (LDH), bulky disease, R-IPI, first-line treatment, salvage treatment, response to treatment, and survival.…”

Section: Methodsmentioning

confidence: 99%

“…[15][16][17][18][19] In DLBCL, TP53 mutation has been identified as an unfavorable prognostic factor for patients under a CHOP or R-CHOP treatment regimen. 12,[20][21][22][23][24][25] In a study of 102 DLBCL patients, the CR rate was significantly higher in patients missing TP53 mut. 25 The prognostic impact of TP53 mut was further investigated in a study with 506 de novo DLBCL patients, and the results showed TP53 mut was an independent predictor of OS and progression-free survival (PFS) in patients treated with an R-CHOP regimen.…”

Section: Introductionmentioning

confidence: 99%

“… 12 , 20–25 In a study of 102 DLBCL patients, the CR rate was significantly higher in patients missing TP53 mut. 25 The prognostic impact of TP53 mut was further investigated in a study with 506 de novo DLBCL patients, and the results showed TP53 mut was an independent predictor of OS and progression-free survival (PFS) in patients treated with an R-CHOP regimen. 23 The prognostic impact of TP53 mut was further confirmed in the RICOVER 60 trial, suggesting the use of TP53 mut for prognostication and treatment stratification.…”

Section: Introductionmentioning

confidence: 99%

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<p>Characteristics and Management of <em>TP53</em>-Mutated Diffuse Large B-Cell Lymphoma Patients</p>

Qin¹,

Jiang²,

Liu³

et al. 2020

CMAR

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Background/Aim TP53 mutation is recognized as a negative prognostic factor for patients with diffuse large B-cell lymphoma (DLBCL). Here, we present the characteristics of TP53 mut DLBCL patients following investigation of the effect of a treatment approach on survival of TP53 mut DLBCL patients. Methods A total of 44 DLBCL patients with TP53 mut and treated with an R-CHOP regimen were included for analysis. Patients who failed to achieve a complete response (CR) to initial treatment or relapsed in the first 6 months after initial CR were deemed to have primary refractory disease. Results Among 44 patients harboring TP53 mutations who underwent upfront R-CHOP or R-CHOP–like treatment, 21 (47.7%) had limited-stage and 23 (52.3%) presented advanced-stage disease. Apart from the seven patients receiving upfront surgical resection, 37 had measurable disease under the R-CHOP regimen, with 59.1% (n=26) developing primary refractory disease. Seven limited-stage patients after early complete resection and one with residue resection remained event-free at median follow-up of 37 months. Multivariate analysis revealed that elevated baseline lactate dehydrogenase (LDH), extranodal involvement (two or more), Ann Arbor stage, and locoregional treatment (surgery or radiation therapy) were independent indicators for progression-free survival (PFS). After adjustment for baseline LDH and extranodal involvement, adding locoregional treatment including surgery and radiation to the R-CHOP regimen significantly improved PFS ( p =0.008) and overall survival ( p =0.017) in limited-stage TP53 mut DLBCL patients compared to R-CHOP–only treatment. Conclusion This study presents the characteristics of TP53 -mutated DLBCL and implies a potential benefit of locoregional treatment in limited-stage DLBCL patients with TP53 mutations.

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“…Studies using next-generation sequencing have characterized the mutational landscape and identified the genetic drivers of DLBCL 7,10,11 . Several gene mutations including MYD88 L265P and CD79B mutations, NOTCH1 mutations, and TP53 mutations are independent risk factors related to poor prognosis in DLBCL patients 7,[10][11][12][13][14][15] . Additionally, recent studies have emphasized the prognostic role of the tumor microenvironment (TME) in DLBCL, and several biomarkers related to the TME have thus been identified [16][17][18][19][20][21] .…”

Section: Introductionmentioning

confidence: 99%

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

Qin¹,

Chen²,

Liu³

et al. 2021

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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.

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Molecular profiling of Chinese R‐CHOP treated DLBCL patients: Identifying a high‐risk subgroup

Cited by 17 publications

References 44 publications

Primary breast double-hit lymphoma management and outcomes: a real-world multicentre experience

Primary breast double-hit lymphoma management and outcomes: a real-world multicentre experience

<p>Characteristics and Management of <em>TP53</em>-Mutated Diffuse Large B-Cell Lymphoma Patients</p>

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

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