Department of Hematology.
Department of Pathology.
Medicine (Baltimore). 2021 Mar 12;100(10):e24824. doi: 10.1097/MD.0000000000024824.
There is currently no optimal treatment modality for refractory or relapsed Extranodal NK/T-cell lymphoma, nasal type (ENKTL). In recent years, programmed cell death protein 1 (PD-1)/programmed cell - ligand 1 pathway blockade and histone deacetylase inhibitors have emerged as promising strategies for refractory or relapsed ENKTL. Accumulating evidence has shown that therapeutic effects of anti-PD-1 antibody could be enhanced by histone deacetylase inhibitors.
A 52-year-old male patient was diagnosed with stage I ENKTL by biopsy on February 2010.
positron emission tomography-computed tomography (PET-CT) and biopsy were used to diagnose relapsed ENKTL in 2014.
The patient was treated with radiotherapy and six cycles of etoposide, prednisone, vincristine (Oncovin), cyclophosphamide and doxorubicin hydrochloride and achieved complete remission (CR) by PET-CT in August 2010. In November 2014, the patient was diagnosed with relapsed stage IV ENKTL and was treated with six cycles of alternative chemotherapy with the regimen of steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide and pegaspargase plus Gemcitabine, Oxaliplatin along with radiotherapy. The patient achieved remission and was placed on thalidomide maintenance treatment. Upon suspicion of relapse suggested by PET-CT, Autologous stem cell transplant was performed after BCNU, etoposide, Ara-C, and melphalan preconditioning on February 2016. Following relapse again in December 2016, the lesions of left femur were treated with radiotherapy and he received anti-PD-1 antibody. He was treated with 4 cycles of pegaspargase plus Gemcitabine, Oxaliplatin on August 2017. The patient's condition improved. He received maintenance and consolidation therapy including lenalidomide, radiotherapy of the right nasal cavity and paranasal sinuses and antigen-specific reactive T cell infusions. PET-CT imaging showed there was high metabolic activity signal in the distal end of right femoral on August 2018 and the treatment regimen was adjusted to radiotherapy of the distal end of right femoral and systemic treatment of PD-1 antibody Sintilimab and chidamide 30 mg. After 5 months post-treatment, biopsy of nasopharynx showed no lymphoma cells. The patient continued the treatment of Sintilimab and chidamide 20 mg.
PET-CT imaging showed his lesions obtained remission after 8 months post-treatment.
Thus, combination of sintilimab and chidamide can be used to treat relapsed ENKTL following treatment failure from chemo-, radio-, and immuno-therapy. A clinical trial has been launched.
目前,对于复发/难治性结外 NK/T 细胞淋巴瘤,鼻型(ENKTL)尚无最佳的治疗方法。近年来,程序性死亡蛋白 1(PD-1)/程序性死亡配体 1 通路阻断和组蛋白去乙酰化酶抑制剂已成为治疗复发/难治性 ENKTL 的有前途的策略。越来越多的证据表明,抗 PD-1 抗体的治疗效果可以通过组蛋白去乙酰化酶抑制剂增强。
一名 52 岁男性患者于 2010 年 2 月通过活检被诊断为 I 期 ENKTL。
2014 年通过正电子发射断层扫描-计算机断层扫描(PET-CT)和活检诊断为复发 ENKTL。
该患者接受了放疗和 6 个周期的依托泊苷、泼尼松、长春新碱(Oncovin)、环磷酰胺和多柔比星治疗,并于 2010 年 8 月通过 PET-CT 达到完全缓解(CR)。2014 年 11 月,该患者被诊断为复发的 IV 期 ENKTL,并接受了 6 个周期的替代化疗,方案为类固醇(地塞米松)、甲氨蝶呤、异环磷酰胺、左旋门冬酰胺酶和依托泊苷,以及培门冬酶加吉西他滨、奥沙利铂联合放疗。该患者达到缓解,并接受沙利度胺维持治疗。在 PET-CT 提示疑似复发后,于 2016 年 2 月在 BCNU、依托泊苷、阿糖胞苷和马法兰预处理后进行了自体干细胞移植。2016 年 12 月再次复发后,对左侧股骨的病变进行了放疗,并且他接受了抗 PD-1 抗体治疗。2017 年 8 月,他接受了 4 个周期的培门冬酶加吉西他滨、奥沙利铂治疗。患者病情改善。他接受了维持和巩固治疗,包括来那度胺、右鼻腔和鼻旁窦的放疗以及抗原特异性反应性 T 细胞输注。2018 年 8 月 PET-CT 成像显示右侧股骨远端有高代谢活性信号,治疗方案调整为右侧股骨远端放疗和 PD-1 抗体信迪利单抗和西达本胺 30mg 的全身治疗。治疗后 5 个月,鼻咽活检显示无淋巴瘤细胞。患者继续接受信迪利单抗和西达本胺 20mg 的治疗。
PET-CT 成像显示,患者在治疗后 8 个月时病变获得缓解。
因此,在化疗、放疗和免疫治疗失败后,西达本胺联合信迪利单抗可用于治疗复发/难治性 ENKTL。目前已开展一项临床试验。