Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
Harvard Medical School, Boston, Massachusetts, USA.
Am J Hematol. 2021 Dec 1;96(12):1563-1568. doi: 10.1002/ajh.26338. Epub 2021 Sep 10.
Chemotherapy-induced thrombocytopenia (CIT) is a common complication of cancer treatment. Evidence has emerged supporting use of romiplostim to treat CIT but predicting clinical response to romiplostim is not possible. To determine utility of endogenous thrombopoietin (TPO) as a biomarker of romiplostim response, we performed an observational cohort study of patients with CIT and known baseline TPO levels receiving romiplostim. For weekly on-romiplostim platelet (Plt) count assessment, clinical response was defined as Plt ≥ 75 × 10 /L and ≥ 30 × 10 /L above pretreatment baseline. Overall, moderate, and superior classes of treatment response were defined based on fraction of Plt assessments meeting clinical response criteria (> 0, ≥ 0.6, and ≥ 0.8, respectively). Sixty-three patients with CIT were included; median age was 62 years, 41.3% were female, and median (IQR) romiplostim treatment duration was 14 (4-38) weeks. Median (IQR) TPO was lower in patients achieving moderate response to romiplostim vs those who did not, 234 (135-1085) pg/mL vs 665 (244-1970) pg/mL (p = .034) and lower still in patients achieving superior response vs those who did not, 212 (91-690) pg/mL versus 559 (173-1851) pg/mL (p = .023). Negative correlations were found between TPO level and baseline Plt and TPO level and response fraction. A positive correlation was found between TPO level and lowest effective romiplostim dose. In receiver operating characteristic (ROC) analysis, optimally discriminant TPO level thresholds (as defined by Youden's Index) were ≤ 457 pg/mL for moderate response and ≤ 260 pg/mL for superior response. In conclusion, TPO levels predict response to romiplostim in CIT, with lower levels predicting improved probability and depth of response.
化疗引起的血小板减少症（CIT）是癌症治疗的常见并发症。有证据表明，使用罗米司亭治疗 CIT 是有效的，但预测罗米司亭的临床反应是不可能的。为了确定内源性血小板生成素（TPO）作为罗米司亭反应生物标志物的效用，我们对接受罗米司亭治疗且已知基线 TPO 水平的 CIT 患者进行了一项观察性队列研究。每周对 romiplostim 治疗后的血小板（Plt）计数进行评估，临床反应定义为 Plt ≥ 75×10 /L 和 Plt 高于治疗前基线水平≥ 30×10 /L。总体而言，根据满足临床反应标准的 Plt 评估分数，将治疗反应分为中度、良好和优秀三个等级（分别为> 0、≥ 0.6 和≥ 0.8）。共纳入 63 例 CIT 患者；中位年龄为 62 岁，41.3%为女性，罗米司亭治疗中位（IQR）时间为 14（4-38）周。与未达到中度 romiplostim 反应的患者相比，达到中度 romiplostim 反应的患者的 TPO 中位数（IQR）更低，分别为 234（135-1085）pg/ml 和 665（244-1970）pg/ml（p =.034），与未达到优越反应的患者相比，达到优越反应的患者的 TPO 中位数（IQR）更低，分别为 212（91-690）pg/ml 和 559（173-1851）pg/ml（p =.023）。TPO 水平与基线血小板和 TPO 水平与反应分数呈负相关。TPO 水平与最低有效 romiplostim 剂量呈正相关。在受试者工作特征（ROC）分析中，最优区分 TPO 水平阈值（由 Youden 指数定义）为中度反应的≤457pg/ml 和优越反应的≤260pg/ml。总之，TPO 水平可预测 CIT 对 romiplostim 的反应，较低的水平预示着反应的可能性和深度提高。
