Yale University School of Medicine, New Haven, United States.
Hematology and Stem Cell Transplantation, Yale University School of Medicine, New Haven, United States.
Expert Rev Anticancer Ther. 2021 Sep;21(9):1017-1028. doi: 10.1080/14737140.2021.1882859. Epub 2021 Jul 27.
The most common types of CTCL are mycosis fungoides (MF) and Sézary syndrome (SS). In both MF and SS, complete responses to treatment are uncommon. Recent developments and understanding of the biology of MF/SS have led to novel agents which may offer prolonged responses with less toxicity compared to conventional chemotherapy approaches.
In this review, we discuss the efficacy and safety of new nonchemotherapy treatment options including antibody agents, small molecule inhibitors, fusion proteins, and CAR T-cell therapy. We also reflect on older immunomodulatory treatments including retinoids and histone deacetylase inhibitors.
Patients with MF/SS who require systemic therapy often progress through multiple agents sequentially, thus the need for additional novel agents in the treatment armamentarium. Antibody-based therapies such as alemtuzumab are highly effective in the blood compartment of disease, while brentuximab vedotin has shown higher activity in skin and lymph nodes. Checkpoint inhibitors may play a role in treating MF/SS but may induce hyperprogression, and engineered T cells and bispecific antibodies recruiting immune effectors are being developed and may show promise in the future.
蕈样真菌病(MF)和赛泽里综合征(SS)是最常见的 CTCL 类型。在 MF 和 SS 中,治疗的完全缓解并不常见。MF/SS 生物学的最新发展和认识导致了新型药物的出现,与传统化疗方法相比,这些药物可能具有更长的缓解期和更少的毒性。
在这篇综述中,我们讨论了新型非化疗治疗选择的疗效和安全性,包括抗体药物、小分子抑制剂、融合蛋白和 CAR T 细胞疗法。我们还回顾了包括类视黄醇和组蛋白去乙酰化酶抑制剂在内的较老的免疫调节治疗。
经常需要系统治疗的 MF/SS 患者通常会按顺序使用多种药物,因此治疗手段中需要额外的新型药物。基于抗体的疗法,如阿仑单抗,在疾病的血液成分中具有高度疗效,而 Brentuximab vedotin 在皮肤和淋巴结中显示出更高的活性。检查点抑制剂可能在治疗 MF/SS 中发挥作用,但可能会诱导过度进展,正在开发工程 T 细胞和双特异性抗体招募免疫效应物,它们在未来可能具有前景。