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 × 10⁹/L and ≥ 30 × 10⁹/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.

中文翻译：

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血小板生成素水平可预测化疗引起的血小板减少症对罗米司亭治疗的反应

化疗引起的血小板减少症 (CIT) 是癌症治疗的常见并发症。已有证据支持使用罗米司亭治疗 CIT，但无法预测罗米司亭的临床反应。为了确定内源性血小板生成素 (TPO) 作为 romiplostim 反应的生物标志物的效用，我们对接受 romiplostim 的 CIT 和已知基线 TPO 水平患者进行了一项观察性队列研究。对于每周一次 romiplostim 血小板 (Plt) 计数评估，临床反应定义为 Plt ≥ 75 × 10 ⁹ /L 和 ≥ 30 × 10 ⁹/L 高于预处理基线。总体而言，根据满足临床反应标准（分别为 > 0、≥ 0.6 和 ≥ 0.8）的 Plt 评估分数，定义了中等和高级类别的治疗反应。包括 63 名 CIT 患者；中位年龄为 62 岁，41.3% 为女性，中位 (IQR) romiplostim 治疗持续时间为 14 (4-38) 周。对 romiplostim 达到中等反应的患者的中位 (IQR) TPO 低于未达到中等反应的患者，234 (135–1085) pg/mL vs 665 (244–1970) pg/mL ( p  = .034) 并且在患者中更低与那些没有达到更好的反应，212 (91–690) pg/mL 对 559 (173–1851) pg/mL ( p = .023）。发现 TPO 水平与基线 Plt 和 TPO 水平与响应分数之间呈负相关。在 TPO 水平和最低有效 romiplostim 剂量之间发现正相关。在接受者操作特征 (ROC) 分析中，最佳判别 TPO 水平阈值（由约登指数定义）为 ≤ 457 pg/mL 为中等反应，≤ 260 pg/mL 为卓越反应。总之，TPO 水平预测 CIT 中对 romiplostim 的反应，较低水平预测改善的概率和反应深度。