Department of Pharmacy, Mie University Hospital, Mie, Japan.
Department of Obstetrics and Gynecology, Mie University School of Medicine, Mie, Japan.
Medicine (Baltimore). 2023 Jul 28;102(30):e34123. doi: 10.1097/MD.0000000000034123.
Anemia is the most common dose-limiting toxicity of olaparib. However, few studies have analyzed the clinical features of olaparib-induced anemia. This study investigated the clinical features of olaparib-induced anemia. Additionally, the role of folate or vitamin B12 in olaparib-induced anemia was examined. This retrospective case-control study included patients who received olaparib at Mie University Hospital between January 2018 and December 2020. Data were collected between initiation of olaparib and discontinuation of olaparib or till December 2021. We investigated the development of grade ≥ 3 anemia during olaparib administration for at least 1 year. We examined patients with grade ≥ 3 anemia considering the mean corpuscular volume (MCV), its association with gastrointestinal events and cumulative dose of carboplatin. For the sub-study analysis, data on patients treated with olaparib for ovarian or endometrial cancer were collected to evaluate the Common Terminology Criteria for Adverse Events (CTCAE) or monthly changes in folate or vitamin B12 levels from baseline to 3 months after olaparib initiation. These data were collected between initiation of olaparib and discontinuation of olaparib or till November 2022. Patients with no data on folic acid or vitamin B12 levels were excluded from the sub-study. In the main study, 40 patients were included. Eighteen patients (45%) developed grade ≥ 3 anemia, and all patients discontinued treatment (94%) or reduced olaparib dose (67%) after developing anemia. Among the patients with grade ≥ 3 anemia, 9 (50%) exhibited macrocytic anemia and 15 (83%) had previously received carboplatin. The incidence of grade ≥ 2 dysgeusia was significantly higher in patients with grade ≥ 3 anemia (P = .034). Moreover, the cumulative dose of previously administered carboplatin was higher in patients who had 3 episodes of anemia (P = .102). In sub-study, 12 had data on folic acid and vitamin B12 levels. Sub-study analysis showed that none fulfilled the criteria for deficiency of folate or vitamin B12, while 3 developed grade 3 anemia. This study revealed that olaparib-induced anemia frequently occurs as macrocytic and normocytic erythroblastic anemia without folate or vitamin B12 deficiencies. A high cumulative dose of previously administered carboplatin and dysgeusia may be associated with olaparib-induced anemia.
贫血是奥拉帕利治疗中最常见的剂量限制毒性。然而，很少有研究分析奥拉帕利诱导的贫血的临床特征。本研究探讨了奥拉帕利诱导的贫血的临床特征。此外，还研究了叶酸或维生素 B12 在奥拉帕利诱导的贫血中的作用。这项回顾性病例对照研究纳入了 2018 年 1 月至 2020 年 12 月在日本三重大学医院接受奥拉帕利治疗的患者。数据收集于奥拉帕利开始治疗至停药或 2021 年 12 月期间。我们调查了至少 1 年期间接受奥拉帕利治疗期间发生 3 级以上贫血的情况。我们检查了贫血患者的平均红细胞体积（MCV），及其与胃肠道事件的关系和卡铂累积剂量。对于子研究分析，收集了接受奥拉帕利治疗卵巢癌或子宫内膜癌患者的数据，以评估不良事件通用术语标准（CTCAE）或从奥拉帕利开始至 3 个月后叶酸或维生素 B12 水平的每月变化。这些数据收集于奥拉帕利开始治疗至停药或 2022 年 11 月期间。排除了没有叶酸或维生素 B12 水平数据的患者。在主要研究中，纳入了 40 名患者。18 名患者（45%）出现 3 级以上贫血，所有患者在出现贫血后停止治疗（94%）或减少奥拉帕利剂量（67%）。在出现 3 级以上贫血的患者中，9 名（50%）患者表现为巨细胞性贫血，15 名（83%）患者曾接受卡铂治疗。发生 3 级以上贫血的患者中，味觉障碍发生率显著更高（P=0.034）。此外，既往接受的卡铂累积剂量在发生 3 次贫血的患者中更高（P=0.102）。在子研究中，有 12 名患者的数据涉及叶酸和维生素 B12 水平。子研究分析表明，没有患者符合叶酸或维生素 B12 缺乏的标准，然而有 3 名患者出现 3 级贫血。本研究表明，奥拉帕利诱导的贫血常表现为巨幼细胞性和正细胞性红细胞性贫血，而无叶酸或维生素 B12 缺乏。既往接受的卡铂累积剂量较高和味觉障碍可能与奥拉帕利诱导的贫血相关。
