Haematology Department, Royal North Shore Hospital, Sydney.
National Centre for Infection in Cancer.
Curr Opin Infect Dis. 2019 Dec;32(6):538-545. doi: 10.1097/QCO.0000000000000611.
With the introduction of new targeted therapies for hematological malignancies comes the challenges of both assessing the risk of developing an IFD while being treated with these agents, as well as managing the drug--drug interactions between azole antifungals and the agents.
New targeted therapies for hematological malignancy include chimeric antigen receptor T cells (CAR T cells), Bi-specific T-cell Engager (BiTE) blinatumomab, and the antibody-drug conjugate (ADC) of calicheamicin inotuzumab ozogamicin for acute lymphoblasic leukemia (ALL) and lymphoma; the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib and phosphatidylinositol 3-kinase (PI3Kδ) inhibitor idelalisib for lymphoma and graft-versus-host disease (GVHD); FMS-like tyrosine kinase 3 (FLT3) inhibitors, such as midostaurin, sorafenib and gilteritinib for acute myeloid leukemia (AML); and the BCL-2 inhibitor venetoclax for a range of hematological malignancies including lymphoma and leukemia. This review summarizes recommendations for IFD prophylaxis using these therapies and evidence for managing concomitant azole administration.
Whilst some evidence exists to guide IFD prophylaxis using new targeted therapies for hematological malignancies, there is an overall lack of descriptive, robust studies specifically describing IFD risk and management. With the emergence of novel agents, clinical judgment must be used to assess the risk of developing an IFD. Care must also be taken when administering azoles with drug--drug interactions, often requiring dose adjustment of the cancer therapies.
综述目的：随着针对血液系统恶性肿瘤的新型靶向治疗药物的出现，既要评估这些药物治疗时发生 IFD 的风险，又要管理唑类抗真菌药与药物之间的药物相互作用，这给临床带来了新的挑战。
最近发现：针对血液系统恶性肿瘤的新型靶向治疗药物包括嵌合抗原受体 T 细胞（CAR-T 细胞）、双特异性 T 细胞衔接器（BiTE）blinatumomab、以及 calicheamicin 的抗体药物偶联物（ADC）inotuzumab ozogamicin，用于治疗急性淋巴细胞白血病（ALL）和淋巴瘤；布鲁顿酪氨酸激酶（BTK）抑制剂伊布替尼和磷脂酰肌醇 3-激酶（PI3Kδ）抑制剂idelalisib，用于治疗淋巴瘤和移植物抗宿主病（GVHD）；FMS 样酪氨酸激酶 3（FLT3）抑制剂，如 midostaurin、sorafenib 和 gilteritinib，用于治疗急性髓细胞白血病（AML）；BCL-2 抑制剂 venetoclax 用于治疗包括淋巴瘤和白血病在内的一系列血液系统恶性肿瘤。本文综述了这些治疗药物的 IFD 预防建议，以及同时使用唑类药物的管理证据。
总结：虽然有一些证据可以指导针对血液系统恶性肿瘤的新型靶向治疗药物进行 IFD 预防，但总体上缺乏描述性的、针对 IFD 风险和管理的强有力研究。随着新型药物的出现，必须运用临床判断来评估发生 IFD 的风险。在管理具有药物相互作用的唑类药物时，还必须小心谨慎，通常需要调整癌症治疗药物的剂量。
