Clinical Oncology, Janssen Research and Development, San Diego, CA, USA.
Clinical Oncology, Janssen Research and Development, Raritan, NJ, USA.
Br J Haematol. 2021 Jul;194(1):83-91. doi: 10.1111/bjh.17450. Epub 2021 May 3.
We assessed the concordance between immunohistochemistry (IHC) and gene expression profiling (GEP) for determining diffuse large B-cell lymphoma (DLBCL) cell of origin (COO) in the phase III PHOENIX trial of rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) with or without ibrutinib. Among 910 of 1114 screened patients with non-germinal centre B cell-like (non-GCB) DLBCL by IHC, the concordance with GEP for non-GCB calls was 82·7%, with 691 (75·9%) identified as activated B cell-like (ABC), and 62 (6·8%) as unclassified. Among 746 of 837 enrolled patients with verified non-GCB DLBCL by IHC, the concordance with GEP was 82·8%, with 567 (76·0%) identified as ABC and 51 (6·8%) unclassified; survival outcomes were similar regardless of COO or treatment, whereas among patients with ABC DLBCL aged <60 years, the overall and event-free survival were substantially better with ibrutinib versus placebo plus R-CHOP [hazard ratio (HR) 0·365, 95% confidence interval (CI) 0·147-0·909, P = 0·0305; HR 0·561, 95% CI 0·326-0·967, P = 0·0348, respectively]. IHC and GEP showed high concordance and consistent survival outcomes among tested patients, indicating centralised IHC may be used to enrich populations for response to ibrutinib plus R-CHOP.
我们评估了免疫组织化学（IHC）和基因表达谱分析（GEP）在 III 期 PHOENIX 试验中的一致性，该试验比较了利妥昔单抗联合环磷酰胺、多柔比星、长春新碱和泼尼松（R-CHOP）与或不联合伊布替尼治疗弥漫性大 B 细胞淋巴瘤（DLBCL）的细胞起源（COO）。在通过 IHC 筛选的 1114 例非生发中心 B 细胞样（non-GCB）DLBCL 患者中，有 910 例患者进行了 GEP 检测，其非 GCB 分类的一致性为 82.7%，其中 691 例（75.9%）被鉴定为激活 B 细胞样（ABC），62 例（6.8%）为未分类。在通过 IHC 验证的 837 例有明确的 non-GCB DLBCL 患者中，有 746 例进行了 GEP 检测，其一致性为 82.8%，其中 567 例（76.0%）被鉴定为 ABC，51 例（6.8%）为未分类。无论 COO 或治疗如何，生存结果相似，而在年龄<60 岁的 ABC DLBCL 患者中，与安慰剂联合 R-CHOP 相比，伊布替尼显著改善了总生存期和无事件生存期[风险比（HR）0.365，95%置信区间（CI）0.147-0.909，P=0.0305；HR 0.561，95%CI 0.326-0.967，P=0.0348]。在接受检测的患者中，IHC 和 GEP 显示出高度一致性和一致的生存结果，这表明集中的 IHC 可能用于富集对伊布替尼联合 R-CHOP 有反应的人群。
