Div of Hematology Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
Hematology Division, Brigham and Womens Hospital, Boston, USA.
Haematologica. 2021 Apr 1;106(4):1148-1157. doi: 10.3324/haematol.2020.251900.
Chemotherapy-induced thrombocytopenia (CIT) frequently complicates cancer treatment causing chemotherapy delays, dose reductions, and discontinuation. There is no FDA-approved agent available to manage CIT. This study retrospectively evaluated patients with CIT treated on institutional romiplostim treatment pathways at 4 U.S. centers. The primary outcome was achievement of a romiplostim response [median on-romiplostim platelet count (Plt) ≥75x109/L and ≥30x109/L above baseline]. Secondary outcomes included time to Plt≥100x109/L and rates of the following: Plt<100x109/L, Plt<75x109/L, Plt<50x109/L, thrombocytosis, chemotherapy dose reduction/treatment delay, platelet transfusion, bleeding, and thromboembolism. Multivariable regression was used to identify predictors of romiplostim non-response and compare weekly dosing with intracycle/intermittent dosing. 173 patients (153 solid tumor, 20 lymphoma or myeloma) were treated, with 170 (98%) receiving a median of 4 (range, 1-36) additional chemotherapy cycles on romiplostim. Romiplostim was effective in solid tumor patients: 71% of patients achieved a romiplostim response, 79% avoided chemotherapy dose reductions/treatment delays and 89% avoided platelet transfusions. Median per-patient Plt on romiplostim was significantly higher than baseline (116x109/L vs. 60x109/L, P<0.001). Bone marrow tumor invasion, prior pelvic irradiation, and prior temozolomide predicted romiplostim non-response. Bleeding rates were lower than historical CIT cohorts and thrombosis rates were not elevated. Weekly dosing was superior to intracycle dosing with higher response rates and less chemotherapy dose reductions/treatment delays (IRR 3.00, 95% CI 1.30-6.91, P=0.010) or bleeding (IRR 4.84, 95% CI 1.18-19.89, P=0.029). Blunted response (10% response rate) was seen in non-myeloid hematologic malignancy patients with bone marrow involvement. In conclusion, romiplostim was safe and effective for CIT in most solid tumor patients.
化疗诱导的血小板减少症（CIT）常使癌症治疗复杂化，导致化疗延迟、剂量减少和停药。目前还没有获得 FDA 批准的药物来治疗 CIT。本研究回顾性评估了在美国 4 个中心接受机构 romiplostim 治疗方案治疗的 CIT 患者。主要结局是 romiplostim 应答的实现[中位数 romiplostim 治疗后血小板计数（Plt）≥75x109/L，比基线水平升高≥30x109/L]。次要结局包括达到 Plt≥100x109/L 的时间以及以下情况的发生率：Plt<100x109/L、Plt<75x109/L、Plt<50x109/L、血小板增多症、化疗剂量减少/治疗延迟、血小板输注、出血和血栓栓塞。多变量回归用于确定 romiplostim 无应答的预测因素，并比较每周剂量与周期内/间歇剂量。173 名患者（153 名实体瘤患者，20 名淋巴瘤或骨髓瘤患者）接受了治疗，其中 170 名（98%）患者在 romiplostim 治疗期间接受了中位数为 4（范围，1-36）个额外的化疗周期。在实体瘤患者中，romiplostim 有效：71%的患者达到 romiplostim 应答，79%避免了化疗剂量减少/治疗延迟，89%避免了血小板输注。romiplostim 治疗后每名患者的 Plt 中位数显著高于基线水平（116x109/L 比 60x109/L，P<0.001）。骨髓肿瘤浸润、盆腔放疗史和替莫唑胺治疗史预测 romiplostim 无应答。出血率低于 CIT 历史队列，血栓形成率未升高。与周期内剂量相比，每周剂量具有更高的反应率和更少的化疗剂量减少/治疗延迟（IRR 3.00，95%CI 1.30-6.91，P=0.010）或出血（IRR 4.84，95%CI 1.18-19.89，P=0.029）。骨髓受累的非髓性血液恶性肿瘤患者出现反应迟钝（10%的反应率）。总之，romiplostim 对大多数实体瘤患者的 CIT 是安全有效的。
