PARP抑制剂治疗卵巢癌后的髓系肿瘤

Myeloid neoplasms post PARP inhibitors for ovarian cancer.

作者信息

Caruso Giuseppe, Gigli Federica, Parma Gabriella, Lapresa Mariateresa, Derio Silvia, Palaia Innocenza, Colombo Nicoletta

机构信息

Department of Maternal and Child Health and Urological Sciences, University of Rome La Sapienza, Rome, Italy

Gynecologic Oncology Division, European Institute of Oncology, Milan, Italy.

出版信息

Int J Gynecol Cancer. 2023 Apr 3;33(4):598-606. doi: 10.1136/ijgc-2022-004190.

Abstract

The incidence of myeloid neoplasms following treatment with poly (ADP-ribose) polymerase inhibitors (PARPi) in patients with ovarian cancer has been gradually increasing over the last few years. The cumulative exposure to PARPi and the improved overall survival of patients with ovarian cancer may represent key underlying explanations behind such trend. Fortunately, the earlier introduction of PARPi in the frontline setting reduces the risk of developing secondary myeloid neoplasms. The etiopathogenesis is still unclear but is likely to be multifactorial. The first 2 years of PARPi exposure seem to be the critical window for the onset of myeloid neoplasms post PARPi, with persistent cytopenia recognized as an early warning sign. Despite intensive treatment strategies, the outcome remains poor. There is an unmet clinical need to learn how to minimize risk, make an early diagnosis, and manage myeloid neoplasms post PARPi. First, decision making regarding the optimal maintenance treatment should avoid a 'PARPi-for-all' strategy. PARPi should be used cautiously in cases of high baseline risk for myeloid neoplasms and/or patients who are less likely to have a benefit. Active surveillance, accurate differential diagnosis, and prompt hematological referral are key management pillars. This review discusses what is known on this emerging issue as well as unresolved questions.

摘要

在过去几年中,卵巢癌患者接受聚(ADP - 核糖)聚合酶抑制剂(PARPi)治疗后发生髓系肿瘤的发生率逐渐上升。PARPi的累积暴露以及卵巢癌患者总体生存率的提高可能是这种趋势背后的关键潜在原因。幸运的是,在一线治疗中更早引入PARPi可降低发生继发性髓系肿瘤的风险。其发病机制仍不清楚,但可能是多因素的。PARPi暴露的头两年似乎是PARPi治疗后髓系肿瘤发病的关键窗口期,持续性血细胞减少被认为是一个早期预警信号。尽管采取了强化治疗策略,但其预后仍然很差。如何将风险降至最低、进行早期诊断以及管理PARPi治疗后的髓系肿瘤,这一临床需求尚未得到满足。首先,关于最佳维持治疗的决策应避免采用“一刀切的PARPi治疗”策略。对于髓系肿瘤基线风险高和/或获益可能性较小的患者,应谨慎使用PARPi。主动监测、准确的鉴别诊断和及时的血液科转诊是关键的管理支柱。本综述讨论了关于这一新兴问题的已知情况以及未解决的问题。

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