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Molecular profiling of Chinese R‐CHOP treated DLBCL patients: Identifying a high‐risk subgroup
Author(s) -
Jiang Shiyu,
Qin Yan,
Jiang Hongxin,
Liu Biao,
Shi Jianming,
Meng Fanlu,
Liu Peng,
Yang Jianliang,
Yang Sheng,
He Xiaohui,
Zhou Shengyu,
Gui Lin,
Liu Hao,
Lin Jing,
HanZhang Han,
Shi Yuankai
Publication year - 2020
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.33049
Subject(s) - medicine , hazard ratio , diffuse large b cell lymphoma , oncology , lymphoma , gastroenterology , rituximab , mutation , refractory (planetary science) , cancer research , biology , gene , genetics , confidence interval , astrobiology
Diffuse large B‐cell lymphoma (DLBCL) is a clinically aggressive and heterogenous disease. Although most patients can be cured by immunochemotherapy, 30% to 40% patient will ultimately develop relapsed or refractory disease. Here, we investigated the molecular landscapes of patients with diverse responses to R‐CHOP. We performed capture‐based targeted sequencing on baseline samples of 105 DLBCL patients using a panel consisting of 112 lymphoma‐related genes. Subsequently, 81 treatment‐naïve patients with measurable disease and followed for over 1 year were included for survival analysis. Collectively, the most commonly seen mutations included IGH fusion (69%), PIM1 (33%), MYD88 (29%), BCL2 (29%), TP53 (29%), CD79B (25%) and KMT2D (24%). Patients with TP53 mutations were more likely to have primary refractory disease (87.0% vs 50.0%, P = .009). For those with TP53 disruptive mutations, 91.7% patients were in the primary refractory group. Interestingly, BCL‐2 somatic hypermutation was only seen in patients without primary refractory disease ( P = .014). In multivariate analysis, BCL‐2 amplification (hazard ratio [HR] = 2.94, P = .022), B2M mutation (HR = 2.99, P = .017) and TP53 mutation (HR = 3.19, P < .001) were independently associated with shorter time to progression (TTP). Furthermore, TP53 mutations was correlated with worse overall survival ( P = .049). Next, we investigated mutation landscape in patients with wild‐type (WT) TP5 3 (n = 58) and found that patients harboring MYD88 L265P had significantly inferior TTP than those with WT or non‐265P ( P = .046). Our study reveals the mutation spectrum of treatment‐naive Chinese DLBCL patients. It also confirms the clinical significance of TP53 mutations and indicates the prognostic value of MYD88 L265P in TP53 WT patients.