Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, USA.
Expert Rev Anticancer Ther. 2021 May;21(5):481-488. doi: 10.1080/14737140.2021.1882857. Epub 2021 Feb 8.
: The treatment landscape of chronic lymphocytic leukemia (CLL) has changed dramatically with the introduction of novel targeted therapies. Phosphoinotiside-3 kinase (PI3K) is a B-cell receptor-associated kinase that is essential for growth, survival and migration of neoplastic B cells and is implicated in disease progression and drug resistance.: PI3K inhibitors idelalisib and duvelisib are approved in therapy of relapsed/refractory (R/R) CLL. In this drug profile review, we focus on duvelisib, an oral inhibitor of PI3Kδ and PI3Kγ isoforms, in treatment of patients with R/R CLL.: Duvelisib, a selective dual PI3Kδ/γ inhibitor, achieves meaningful efficacy in CLL, including in patients with high-risk features. Duvelisib therapy may be particularly appropriate for patients who are suboptimal candidates for Bruton tyrosine kinase inhibitors (BTK), such as those with cardiac conditions, poorly controlled hypertension, or requiring full-dose anticoagulation. Tumor lysis monitoring is not necessary with duvelisib, rendering advantage over the BCL2 inhibitor venetoclax. Patients who progress on both BTK inhibitors and venetoclax may be particularly good candidates for duvelisib therapy. With close monitoring and management of adverse events, duvelisib will continue to have a role in therapy of R/R CLL.
: 慢性淋巴细胞白血病(CLL)的治疗格局随着新型靶向治疗的引入发生了巨大变化。磷酸肌醇 3 激酶(PI3K)是一种 B 细胞受体相关激酶,对肿瘤 B 细胞的生长、存活和迁移至关重要,并与疾病进展和耐药性有关。PI3K 抑制剂idelalisib 和 duvelisib 已被批准用于治疗复发/难治性(R/R)CLL。在本次药物专题报告中,我们重点关注 duvelisib,一种口服 PI3Kδ 和 PI3Kγ 同工型抑制剂,用于治疗 R/R CLL 患者。: Duvelisib 是一种选择性双重 PI3Kδ/γ 抑制剂,在 CLL 中具有显著疗效,包括在具有高危特征的患者中。Duvelisib 治疗可能特别适合那些不适合 Bruton 酪氨酸激酶抑制剂(BTK)的患者,例如有心脏疾病、血压控制不佳或需要全剂量抗凝的患者。Duvelisib 不需要进行肿瘤溶解监测,与 BCL2 抑制剂 venetoclax 相比具有优势。在 BTK 抑制剂和 venetoclax 均进展的患者中,duvelisib 可能是特别好的治疗选择。通过密切监测和管理不良反应,duvelisib 将继续在 R/R CLL 的治疗中发挥作用。