Freyer Craig W, Hughes Mitchell E, Carulli Alison, Bagg Adam, Hexner Elizabeth
Department of Pharmacy Services, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
Department of Medicine, Division of Hematology/Oncology, Perelman School of Medicine and the Hospital of the University of Pennsylvania, University of Pennsylvania, Philadelphia, PA, USA.
Expert Rev Anticancer Ther. 2023 Apr;23(4):351-359. doi: 10.1080/14737140.2023.2192930. Epub 2023 Mar 29.
Myeloid/lymphoid neoplasms with fibroblast growth factor receptor-1 () rearrangements (MLN) are rare entities with aggressive features and poor prognosis. Presentation is heterogeneous, ranging from myeloproliferative neoplasms (with or without eosinophilia) to T-cell lymphoma and acute leukemia. Historical treatments have been guided by the presenting phenotype with induction chemotherapy frequently used. Pemigatinib is a FGFR1-3 tyrosine kinase inhibitor that has demonstrated high complete hematologic and cytogenetic response rates in MLN.
We discuss the pathogenesis, presentation, and historical treatments for MLN, in addition to clinical data using pemigatinib and other targeted therapies. Discussion of the mechanism of action and adverse events is also included.
Pemigatinib represents a significant advance in the management of MLN. High rates of complete hematologic and cytogenetic response have been observed. While direct comparative data are unavailable, outcomes appear favorable compared to conventional approaches. Long-term efficacy and tolerability are not yet known, and allogeneic hematopoietic stem cell transplant (alloHSCT) continues to be the treatment with the highest chance of long-term disease free survival in responding patients. Combinations of pemigatinib and chemotherapy, particularly for more aggressive phenotypes, warrant future investigation as does the use of pemigatinib maintenance following alloHSCT.
伴有成纤维细胞生长因子受体1（FGFR1）重排的髓系/淋系肿瘤（MLN）是罕见的疾病，具有侵袭性特征且预后较差。临床表现具有异质性，范围从骨髓增殖性肿瘤（伴或不伴嗜酸性粒细胞增多）到T细胞淋巴瘤和急性白血病。既往治疗一直以呈现的表型为指导，经常使用诱导化疗。培米替尼是一种FGFR1-3酪氨酸激酶抑制剂，已在MLN中显示出较高的完全血液学和细胞遗传学缓解率。
我们除了讨论使用培米替尼和其他靶向疗法的临床数据外，还讨论了MLN的发病机制、临床表现和既往治疗方法。还包括对作用机制和不良事件的讨论。
培米替尼在MLN的治疗方面取得了重大进展。已观察到较高的完全血液学和细胞遗传学缓解率。虽然尚无直接的对比数据，但与传统方法相比，结果似乎更有利。长期疗效和耐受性尚不清楚，异基因造血干细胞移植（alloHSCT）仍然是反应性患者实现长期无病生存机会最高的治疗方法。培米替尼与化疗的联合应用，特别是对于更具侵袭性的表型，值得未来研究，alloHSCT后使用培米替尼维持治疗也值得研究。
