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)
TP53 (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.
相似文献