尼洛替尼一线治疗慢性髓系白血病的进展

doi:10.3760/cma.j.issn.1673-422X.2020.01.011

摘要/Abstract

摘要：

慢性髓系白血病(CML)是一类骨髓增殖性肿瘤,其发病机制与BCR/ABL融合基因相关。酪氨酸激酶抑制剂(TKI)可显著改善CML患者的生存及预后。尼洛替尼一线治疗CML患者疗效显著、治疗反应快、缓解程度深并且安全性高。在获得持续深层分子反应后,实现停止尼洛替尼用药并达到无治疗缓解是CML治疗的新目标。此外,由于疾病耐药及突变的产生,尼洛替尼治疗失败后如何开始新的治疗值得进一步研究。

关键词: 白血病, 髓样, 慢性期, 酪氨酸激酶抑制剂, 尼洛替尼

Abstract:

Chronic myeloid leukemia (CML) is a myeloproliferative tumor whose pathogenesis is related to the BCR/ABL fusion gene. Tyrosine kinase inhibitors (TKIs) can significantly improve the survival and prognosis of CML patients. Nilotinib is effective in first-line treatment of CML patients with rapid response, deep remission and high safety. After achieving a sustained deep molecular response, it is a new therapeutic goal for CML to stop the use of nilotinib and achieve treatment-free remission. In addition, due to disease resistance and mutations, how to start new treatments after nilotinib treatment failure is worth further research.

Key words: Leukemia, myeloid, chronic-phase, Tyrosine kinase inhibitor, Nilotinib

洪梨, 王玉, 张琦, 吕成芳. 尼洛替尼一线治疗慢性髓系白血病的进展[J]. 国际肿瘤学杂志, 2020, 47(1): 56-59.

Hong Li, Wang Yu, Zhang Qi, Lyu Chengfang. Nilotinib in first-line treatment of chronic myeloid leukemia[J]. Journal of International Oncology, 2020, 47(1): 56-59.

参考文献 28

[1]	Jabbour E, Kantarjian H . Chronic myeloid leukemia: 2018 update on diagnosis, therapy and monitoring[J]. Am J Hematol, 2018,93(3):442-459. DOI: 10.1002/ajh.25011.
[2]	Siegel RL, Miller KD, Jemal A . Cancer Statistics, 2017[J]. CA Cancer J Clin, 2017,67(1):7-30. DOI: 10.3322/caac.21583.
[3]	Kaleem B, Shahab S, Ahmed N , et al. Chronic myeloid leukemia-prognostic value of mutations[J]. Asian Pac J Cancer Prev, 2015,16(17):7415-7423. DOI: 10.7314/apjcp.2015.16.17.7415.
[4]	Rosti G, Palandri F, Castagnetti F , et al. Nilotinib for the frontline treatment of Ph(+) chronic myeloid leukemia[J]. Blood, 2009,114(24):4933-4938. DOI: 10.1182/blood-2009-07-232595.
[5]	Gugliotta G, Castagnetti F, Breccia M , et al. Long-term outcome of a phase 2 trial with nilotinib 400 mg twice daily in first-line treatment of chronic myeloid leukemia[J]. Haematologica, 2015,100(9):1146-1150. DOI: 10.3324/haematol.2015.129221.
[6]	Larson RA, Kim DW, Issaragrisil S , et al. Efficacy and safety of nilotinib (NIH) vs imatinib (IM) in patients (pts) with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP): long-term follow-up (f/u) of ENESTnd[J]. Blood, 2014,124(21):4541-4541. DOI: 10.1182/blood.V124.21.4541.4541.
[7]	Saydam G, Haznedaroglu IC, Kaynar L , et al. Frontline nilotinib treatment in Turkish patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: updated results with 2 years of follow-up[J]. Hematology, 2018,23(10):771-777. DOI: 10.1080/10245332.2018.1498167.
[8]	Huguet F, Cayuela JM, Cambier N , et al. Nilotinib efficacy, safety, adherence and impact on quality of life in newly diagnosed patients with chronic myeloid leukaemia in chronic phase: a prospective observational study in daily clinical practice[J]. Br J Haematol, 2019,187(5):615-626. DOI: 10.1111/bjh.16145.
[9]	Hughes TP, Munhoz E, Aurelio Salvino M , et al. Nilotinib dose-optimization in newly diagnosed chronic myeloid leukaemia in chronic phase: final results from ENESTxtnd[J]. Br J Haematol, 2017,179(2):219-228. DOI: 10.1111/bjh.14829.
[10]	Hochhaus A, Rosti G, Cross NC , et al. Frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the European ENEST1st study[J]. Leukemia, 2016,30(1):57-64. DOI: 10.1038/leu.2015.270.
[11]	Hochhaus A, Saglio G, Hughes TP , et al. Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial[J]. Leukemia, 2016,30(5):1044-1054. DOI: 10.1038/leu.2016.5.
[12]	Kuwasaki S, Koga S, Akashi R , et al. Influence of tyrosine kinase inhibitor, nilotinib, on delayed healing of bare-metal stents in superficial femoral arteries[J]. JACC Cardiovasc Interv, 2019,12(10):e85-e86. DOI: 10.1016/j.jcin.2019.02.025.
[13]	Ota S, Matsukawa T, Yamamoto S , et al. Severe adverse events by tyrosine kinase inhibitors decrease survival rates in patients with newly diagnosed chronic-phase chronic myeloid leukemia[J]. Eur J Haematol, 2018,101(1):95-105. DOI: 10.1111/ejh.13081.
[14]	Sasaki K, Lahoti A, Jabbour E , et al. Clinical safety and efficacy of nilotinib or dasatinib in patients with newly diagnosed chronic-phase chronic myelogenous leukemia and pre-existing liver and/or renal dysfunction[J]. Clin Lymphoma Myeloma Leuk, 2016,16(3):152-162. DOI: 10.1016/j.clml.2015.12.003.
[15]	Nakahara R, Sumimoto T, Ogata M , et al. Successful determination of nilotinib dosage by therapeutic drug monitoring in a patient with chronic myeloid leukemia developing hepatic dysfunction: a case report[J]. Clin Case Rep, 2019, 14, 7(7):1419-1421. DOI: 10.1002/ccr3.2191.
[16]	Radich JP, Deininger M, Abboud CN , et al. Chronic myeloid leukemia, version 1.2019, NCCN clinical practice guidelines in onco-logy[J]. J Natl Compr Canc Netw, 2018,16(9):1108-1135. DOI: 10.6004/jnccn.2018.0071.
[17]	Hochhaus A, Saussele S, Rosti G , et al. Chronic myeloid leukaemia: ESMO clinical practice guidelines for diagnosis, treatment and follow-up[J]. Ann Oncol, 2018, 29(Suppl 4): iv261. DOI: 10.1093/annonc/mdy159.
[18]	Hijiya N, Suttorp M . How I treat chronic myeloid leukemia in children and adolescents[J]. Blood, 2019,133(22):2374-2384. DOI: 10.1182/blood.2018882233.
[19]	Ross DM, Masszi T, Gómez Casares MT , et al. Durable treatment-free remission in patients with chronic myeloid leukemia in chronic phasefollowing frontline nilotinib: 96-week update of the ENESTfreedom study[J]. J Cancer Res Clin Oncol, 2018,144(5):945-954. DOI: 10.1007/s00432-018-2604-x.
[20]	Rea D, Nicolini FE, Tulliez M , et al. Discontinuation of dasatinib or nilotinib in chronic myeloid leukemia: interim analysis of the STOP 2G-TKI study[J]. Blood, 2017,129(7):846-854. DOI: 10.1182/blood-2016-09-742205.
[21]	Tang L, Zhang H, Peng YZ , et al. Comparative efficacy and tolerability of front-line treatments for newly diagnosed chronic-phase chronic myeloid leukemia: an update network meta-analysis[J]. BMC Cancer, 2019,19(1):849. DOI: 10.1186/s12885-019-6039-9.
[22]	Flis S, Chojnacki T . Chronic myelogenous leukemia, a still unsolved problem: pitfalls and new therapeutic possibilities[J]. Drug Des Devel Ther, 2019,13:825-843. DOI: 10.2147/DDDT.S191303.
[23]	Cortes JE, Kim DW, Pinilla-Ibarz J , et al. A phase 2 trial of ponatinib in philadelphia chromosome-positive leukemias[J]. N Engl J Med, 2013,369(19):1783-1796. DOI: 10.1056/NEJMoa1306494.
[24]	Cortes JE, Kim DW, Pinilla-Ibarz J , et al. Ponatinib efficacy and safety in Philadelphia chromosome-positive leukemia: final 5-year results of the phase 2 PACE trial[J]. Blood, 2018,132(4):393-404. DOI: 10.1182/blood-2016-09-739086.
[25]	García-Gutiérrez V, Milojkovic D, Hernandez-Boluda JC , et al. Safety and efficacy of bosutinib in fourth-line therapy of chronic myeloid leukemia patients[J]. Ann Hematol, 2019,98(2):321-330. DOI: 10.1007/s00277-018-3507-2.
[26]	Levy MY, McGarry LJ, Huang H , et al. Benefits and risks of ponatinib versus bosutinib following treatment failure of two prior tyrosine kinase inhibitors in patients with chronic phase chronic myeloid leukemia: a matching-adjusted indirect comparison[J]. Curr Med Res Opin, 2019,35(3):479-487. DOI: 10.1080/03007995.2018.1510225.
[27]	Cerveira N, Ferreira RB, Bizarro S , et al. Ponatinib induces a sustained deep molecular response in a chronic myeloid leukaemia patient with an early relapse with a T315I mutation following allogeneic hematopoietic stemcell transplantation: a case report[J]. BMC Cancer, 2018,18(1):1229. DOI: 10.1186/s12885-018-5100-4.
[28]	García-Gutiérrez V, Hernández-Boluda JC . Tyrosine kinase inhibitors available for chronic myeloid leukemia: efficacy and safety[J]. Front Oncol, 2019,9:603. DOI: 10.3389/fonc.2019.00603.