Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA.
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA.
Blood Adv. 2023 Dec 12;7(23):7243-7253. doi: 10.1182/bloodadvances.2023011384.
Genetic subgroups of diffuse large B-cell lymphoma (DLBCL) have been identified through comprehensive genomic analysis; however, it is unclear whether this can be applied in clinical practice. We assessed whether mutations detected by clinical laboratory mutation analysis (CLMA) were predictive of outcomes in patients with newly diagnosed DLBCL/high-grade B-cell lymphoma (HGBL). Patients diagnosed from 2018 to 2022 whose biopsy samples were subjected to CLMA and who received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone or rituximab plus etoposide, prednisolone, vincristine, cyclophosphamide, and doxorubicin were analyzed for overall/complete response rate (ORR/CRR) and estimated progression-free/overall survival (PFS/OS). CLMA was successfully performed in 117 of 122 patient samples (96%), with a median turnaround time of 17 days. Median duration of follow-up was 31.3 months. Of the mutations detected in ≥10% of the samples, only TP53 was associated with both progression and death at 2 years. TP53 mutations were detected in 36% of tumors, and patients with TP53 mutations experienced significantly lower ORR (71% vs 90%; P = .009), CRR (55% vs 77%; P = .01), 2-year PFS (57% vs 77%; P = .006), 2-year OS (70% vs 91%; P = .001), and median OS after relapse (6.1 months vs not yet reached; P = .001) as than those without TP53 mutations. Furthermore, patients with TP53 loss-of-function (LOF) mutations experienced lower rates of 2-year PFS/OS than those with non-LOF mutations and inferior or near-inferior 2-year PFS if harboring high-risk clinicopathologic features. TP53 mutations identified through CLMA can predict for inferior outcomes in patients with newly diagnosed DLBCL/HGBL. Results of CLMA can be used in real time to inform prognosis and/or identify candidates for clinical trials.
弥漫性大 B 细胞淋巴瘤（DLBCL）的遗传亚群已通过全面的基因组分析确定；然而，目前尚不清楚这是否可以应用于临床实践。我们评估了通过临床实验室突变分析（CLMA）检测到的突变是否可预测新诊断的弥漫性大 B 细胞淋巴瘤/高级别 B 细胞淋巴瘤（HGBL）患者的结局。对 2018 年至 2022 年间诊断、活检样本接受 CLMA 且接受利妥昔单抗联合环磷酰胺、多柔比星、长春新碱和泼尼松或利妥昔单抗联合依托泊苷、泼尼松、长春新碱、环磷酰胺和多柔比星治疗的患者进行了总体/完全缓解率（ORR/CRR）和估计的无进展/总生存率（PFS/OS）分析。在 122 例患者样本中的 117 例（96%）成功进行了 CLMA，中位周转时间为 17 天。中位随访时间为 31.3 个月。在≥10%的样本中检测到的突变中，只有 TP53 与 2 年内的进展和死亡均相关。TP53 突变在 36%的肿瘤中检出，且 TP53 突变的患者 ORR（71% vs 90%；P =.009）、CRR（55% vs 77%；P =.01）、2 年 PFS（57% vs 77%；P =.006）、2 年 OS（70% vs 91%；P =.001）和复发后中位 OS（6.1 个月 vs 未达到；P =.001）显著降低。此外，与非 TP53 突变患者相比，具有 TP53 失活（LOF）突变的患者 2 年 PFS/OS 率较低，如果具有高危临床病理特征，则其 2 年 PFS 更差或接近更差。通过 CLMA 确定的 TP53 突变可预测新诊断的 DLBCL/HGBL 患者的不良结局。CLMA 的结果可实时用于告知预后和/或识别临床试验的候选者。
