Combination of anti-PD-1 antibody with P-GEMOX as a potentially effective immunochemotherapy for advanced natural killer/T cell lymphoma.
Combination of anti-PD-1 antibody with P-GEMOX as a potentially effective immunochemotherapy for advanced natural killer/T cell lymphoma.
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抗 PD-1 抗体与 P-GEMOX 的组合作为晚期自然杀伤/T 细胞淋巴瘤的潜在有效免疫化疗
DOI：
10.1038/s41392-020-00331-3
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发表时间：
2020-12-30
影响因子：
39.3
通讯作者：
Cai Q
中科院分区：
文献类型：
--
作者：
Cai J;Liu P;Huang H;Li Y;Ma S;Zhou H;Tian X;Zhang Y;Gao Y;Xia Y;Zhang X;Yang H;Li L;Cai Q
晚期自然杀伤/T细胞淋巴瘤（NKTL）已被证明与目前可用的治疗预后不良。在此，我们报告了抗程序性死亡1（PD-1）抗体与P-GEMOX（培门冬酶、吉西他滨和奥沙利铂）方案在晚期NKTL中的疗效。9例患者接受了6个21天周期的抗PD-1抗体（第1天）、培门冬酶2000 U/m2（第1天）、吉西他滨1 g/m2（第1天和第8天）和奥沙利铂130 mg/m2（第1天）治疗，随后每3周一次进行抗PD-1抗体维持治疗。使用免疫组织化学和下一代测序（NGS）分析在石蜡包埋的治疗前组织样本中测定程序性死亡配体1（PD-L1）表达和遗传改变。采用18氟脱氧葡萄糖正电子发射断层扫描（18 FDG-PET）和计算机断层扫描或磁共振成像评估缓解情况。8例患者表现出显着的反应，包括7个完全缓解和1个部分缓解（总反应率：88.9%）。中位随访10.6个月后，6/9例患者（66.7%）保持完全缓解。最常见的3/4级不良事件为贫血（33.3%）、中性粒细胞减少症（33.3%）和血小板减少症（33.3%）;所有这些不良事件均可管理并消退。免疫化疗在PD-L1阳性表达的患者中产生了较高的缓解率（5/6，83.3%）。NGS分析提示STAT 3/JAK 3/PD-L1变异和ARID 1A突变与免疫化疗疗效相关。DDX 3X突变和KMT 2D、TET 2和BCORL 1表观遗传修饰物的改变可能提示免疫化疗的不良反应。总之，抗PD-1抗体加P-GEMOX方案在晚期NKTL中显示出有希望的疗效。PD-L1表达与特异性遗传改变相结合，可用作预测免疫化疗治疗反应的潜在生物标志物。
Advanced natural killer/T cell lymphoma (NKTL) has demonstrated poor prognosis with currently available therapies. Here, we report the efficacy of anti-programmed death 1 (PD-1) antibody with the P-GEMOX (pegaspargase, gemcitabine, and oxaliplatin) regimen in advanced NKTL. Nine patients underwent six 21-day cycles of anti-PD-1 antibody (day 1), pegaspargase 2000 U/m2(day 1), gemcitabine 1 g/m2(days 1 and 8) and oxaliplatin 130 mg/m2(day 1), followed by anti-PD-1 antibody maintenance every 3 weeks. Programmed death-ligand 1 (PD-L1) expression and genetic alterations were determined in paraffin-embedded pretreatment tissue samples using immunohistochemistry and next-generation sequencing (NGS) analysis. Responses were assessed using18F-fluorodeoxyglucose positron emission tomography (18FDG-PET) and computed tomography or magnetic resonance imaging. Eight patients exhibited significant responses, comprising of seven complete remissions and one partial remission (overall response rate: 88.9%). After a median follow-up of 10.6 months, 6/9 patients (66.7%) remained in complete remission. The most common grade 3/4 adverse events were anemia (33.3%), neutropenia (33.3%), and thrombocytopenia (33.3%); all of which were manageable and resolved. Immunochemotherapy produced a high response rate in patients with positive PD-L1 expression (5/6, 83.3%). NGS analysis suggested thatSTAT3/JAK3/PD-L1alterations andARID1Amutation were associated with immunochemotherapy efficacy. Mutation inDDX3Xand alteration in epigenetic modifiers ofKMT2D,TET2, andBCORL1might indicate a poor response to immunochemotherapy. In conclusion, the anti-PD-1 antibody plus P-GEMOX regimen demonstrated promising efficacy in advanced NKTL. PD-L1 expression combined with specific genetic alterations could be used as potential biomarkers to predict therapeutic responses to immunochemotherapy.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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