外周T细胞淋巴瘤的靶向治疗进展_West China Medical Journal

Authors：

 李娜 ,  邹立群

四川大学华西医院肿瘤中心（成都 610041）;

Corresponding author：

邹立群, Email: zliqun@hotmail.com

Keywords：

外周T细胞淋巴瘤; 化学疗法; 造血干细胞移植; 靶向治疗

DOI：

10.7507/1002-0179.201600534

Video：

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Abstract Full text Figures/Tables Video References Cited by

外周T细胞淋巴瘤（PTCL）是一组起源于胸腺的成熟T细胞的淋巴增殖性疾病。与B细胞淋巴瘤相比，PTCL侵袭性更强、预后更差，治疗上缺乏统一的标准治疗方案。传统化学治疗方案CHOP（环磷酰胺+长春新碱+多柔比星+泼尼松）及CHOP类似方案对PTCL疗效欠佳。造血干细胞移植在PTCL中的应用有限。因此PTCL的治疗正成为淋巴瘤治疗中最具前沿性和挑战性的研究领域。随着临床研究的不断进展，靶向药物在PTCL的治疗上显示出一定的前景。该文就其靶向治疗进行了综述。

Citation： 李娜, 邹立群. 外周T细胞淋巴瘤的靶向治疗进展. West China Medical Journal, 2016, 31(11): 1943-1948. doi: 10.7507/1002-0179.201600534 Copy

1.	Yi SH, An G, Qi JY, et al. The significance of bone marrow involvement in aggressive lymphomas:a retrospective comparison of clinical outcomes between peripheral T cell lymphoma and diffuse large B cell lymphoma in China[J].Acta Haematol, 2010, 124(4):239-244.
2.	Abouyabis AN, Shenoy PJ, Lechowicz MJ, et al. Incidence and outcomes of the peripheral T-cell lymphoma subtypes in the United States[J].Leuk Lymphoma, 2008, 49(11):2099-2107.
3.	Escalón MP, Liu NS, Yang Y, et al. Prognostic factors and treatment of patients with T-cell non-Hodgkin lymphoma:the M. D. Anderson Cancer Center experience[J].Cancer, 2005, 103(10):2091-2098.
4.	Jagadeesh D, Smith MR. Novel targeted therapies in peripheral T cell lymphoma[J].Discov Med, 2013, 15(85):367-378.
5.	安刚, 齐军元, 邱录贵. 外周T细胞淋巴瘤的治疗进展[J].中华血液学杂志, 2008, 29(10):718-720.
6.	Gisselbrecht C, Gaulard P, Lepage E, et al. Prognostic significance of T-cell phenotype in aggressive non-Hodgkin's lymphomas. Groupe d'Etudes des Lymphomes de l'Adulte (GELA)[J].Blood, 1998, 92(1):76-82.
7.	Jagadeesh D, Smith MR. Novel targeted therapies in peripheral T cell lymphoma[J].Discov Med, 2013, 15(85):367-378.
8.	Gallamini A, Stelitano C, Calvi R, et al. Peripheral T-cell lymphoma unspecified (PTCL-U):a new prognostic model from a retrospective multicentric clinical study[J].Blood, 2014, 103(7):2474-2479.
9.	Vose J, Armitage J, Weisenburger D, et al. International peripheral T-cell and natural killer/T-cell lymphoma study:pathology findings and clinical outcomes[J].J Clin Oncol, 2008, 26(25):4124-4130.
10.	Lee J, Suh C, Park YH, et al. Extranodal natural killer T-cell lymphoma, nasal-type:a prognostic model from a retrospective multicenter study[J].J Clin Oncol, 2006, 24(4):612-618.
11.	Kim SJ, Yoon DH, Jaccard A, et al. A prognostic index for natural killer cell lymphoma after non-anthracycline-based treatment:a multicenter, retrospective analysis[J].Lancet Oncol, 2016, 17(3):389-400.
12.	Piccaluga PP, Agostinelli C, Righi SA, et al. Expression of CD52 in peripheral T-cell lymphoma[J].Haematologica, 2007, 92(4):566-567.
13.	Rodig SJ, Abramson JS, Pinkus GS, et al. Heterogeneous CD52 expression among hematologic neoplasms:implications for the use of alemtuzumab (CAMPATH-1H)[J].Clin Cancer Res, 2006, 12(23):7174-7179.
14.	Binder C, Ziepert M, Pfreundschuh M, et al. CHO(E)P-14 followed by alemtuzumab consolidation in untreated peripheral T cell lymphomas:final analysis of a prospective phase Ⅱ trial[J].Ann Hematol, 2013, 92(11):1521-1528.
15.	Weidmann E, Hess G, Chow KU, et al. A phase Ⅱ study of alemtuzumab, fludarabine, cyclophosphamide, and doxorubicin (Campath-FCD) in peripheral T-cell lymphomas[J].Leuk Lymphoma, 2010, 51(3):447-455.
16.	Enblad G, Hagberg H, Erlanson M, et al. A pilot study of alemtuzumab (anti-CD52 monoclonal antibody) therapy for patients with relapsed or chemotherapy-refractory peripheral T-cell lymphomas[J].Blood, 2004, 103(8):2920-2924.
17.	Kim JG, Sohn SK, Chae YS, et al. Alemtuzumab plus CHOP as front-line chemotherapy for patients with peripheral T-cell lymphomas:a phase Ⅱ study[J].Cancer Chemother Pharmacol, 2007, 60(1):129-134.
18.	Forero-Torres A, Leonard JP, Younes A, et al. A phase Ⅱ study of SGN-30(anti-CD30 mAb) in hodgkin lymphoma or systemic anaplastic large cell lymphoma[J].Br J Haematol, 2009, 146(2):171-179.
19.	Francisco JA, Cerveny CG, Meyer DL, et al. cAC10-vcMMAE, an anti-CD30-monomethyl auristatin E conjugate with potent and selective antitumor activity[J].Blood, 2003, 102(4):1458-1465.
20.	Foss FM, Sjak-Shie N, Goy A, et al. A multicenter phase Ⅱ trial to determine the safety and efficacy of combination therapy with denileukindiftitox and cyclophosphamide, doxorubicin, vincristine and prednisone in untreated peripheral T-cell lymphoma:the CONCEPT study[J].Leuk Lymphoma, 2013, 54(7):1373-1379.
21.	Fanale MA, Horwitz SM, Forero-Torres A, et al. Brentuximab vedotin in the front-Line treatment of patients with CD30+ peripheral T-cell lymphomas:results of a phase Ⅰ study[J].J Clin Oncol, 2014(32):3137-3143.
22.	Pro B, Advani R, Brice P, et al. Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma:results of a phase Ⅱ study[J].J Clin Oncol, 2012, 30(18):2190-2196.
23.	D'Amore F, Radford J, Relander T, et al. Phase Ⅱ trial of zanolimumab (HuMax-CD4) in relapsed or refractory noncutaneous peripheral T cell lymphoma[J].Br J Haematol, 2010, 150(5):565-573.
24.	Advani RH, Hong FX, Ganjoo KN, et al. Cardiac toxicity associated with the Anti-VEGF monoclonal antibody bevacizumab (avastin) in combination with CROP (A-CHOP) chemotherapy for peripheral T cell lymphoma (PTCL):the ECOG 2404 trial[J].Blood, 2009, 114(22):1671.
25.	Ishida T, Ogura M, Hatake K, et al. Multicenter phase Ⅱ study of mogamulizumab (KW-0761), a defucosylated anti-CCR4 antibody, in patients with relapsed peripheral and cutaneous T-cell lymphoma[J].Blood, 2012, 120(21):795.
26.	Utsunomiya A, Tobinai K, Yamamoto K, et al. Promising results of an anti-CCR4 antibody, KW-0761, for relapsed Adult T-Cell Leukemia-Lymphoma (ATL)[J].Retrovirology, 2011, 8(1):1.
27.	O'connor OA, Pro B, Pinter-Brown LA, et al. Pralatrexate in patients with relapsed or refractory peripheral T-cell lymphoma:results from the pivotal PROPEL study[J].J Clin Oncol, 2011, 29(9):1182-1189.
28.	Furumai R, Matsuyama A, Kobashi N, et al. FK228(depsipeptide) as a natural prodrug that inhibits class Ⅰ histone deacetylases[J].Cancer Res, 2002, 62(17):4916-4921.
29.	Piekarz R, Wright J, Frye R, et al. Final results of a phase 2 NCI multicenter Study of romidepsin in patients with relapsed peripheral T-cell lymphoma (PTCL)[J].Blood, 2009, 114(22):661-662.
30.	Duvic M, Kim YH, Kuzel TM, et al. The systemic effects of vorinostat in patients (Pts) with cutaneous T-cell lymphoma (CTCL):post-hoc analyses in Pts with high blood tumor burden[J].ASH Annual Meeting Abstr, 2009, 111(Abstr):1709.
31.	Budde LE, Zhang MM, Shustov AR, et al. A phaseⅠstudy of pulse high-dose vorinostat (V) plus rituximab (R), ifosphamide, carboplatin, and etoposide (ICE) in patients with relapsed lymphoma[J].Br J Haematol, 2013, 161(2):183-191.
32.	Foss F, Advain R, Duvic M, et al. A phase Ⅱ trial of belinostat (PXD101) in patients with relapsedor refractory peripheral or cutaneous T-cell lymphoma[J].Br J Haematol, 2015, 168(6):811-819.
33.	Shi Y, Dong M, Hong X, et al. Results from a multicenter, open-label, pivotal phase Ⅱ study of chidamide in relapsed or refractory peripheral T-cell lymphoma[J].Ann Oncol, 2015, 26(8):1766-1771.
34.	Kim SJ, Yoon DH, Kang HJ, et al. Bortezomib in combination with CHOP as first-line treatment for patients with stage Ⅲ/Ⅳ peripheral T-cell lymphomas:a multicentre, single-arm, phase 2 trial[J].Eur J Cancer, 2012, 48(17):3223-3231.
35.	Delmer A, Fitoussi O, Gaulard P, et al. A phase Ⅱ study of bortezomib in combination with intensified CHOP-like regimen (ACVBP) in patients with previously untreated T-cell lymphoma:results of the GELA LNH05-1T trial[J].J Clin Oncol, 2009, 27(15S):8554.
36.	Friedberg JW, Mahadevan D, Cebula EA, et al. Phase Ⅱ study of alisertib, a selective Aurora a kinase inhibitor, in relapsed and refractory aggressive B-and T-Cell Non-Hodgkin lymphomas[J].J Clin Oncol, 2014, 32(1):44-50.
37.	Hopfinger G, Nösslinger T, Lang A, et al. Lenalidomide in combination with vorinostat and dexamethasone for the treatment of relapsed/refractory peripheral T cell lymphoma (PTCL):report of a phase Ⅰ/Ⅱ trial[J].Ann Hematol, 2014, 93(3):459-462.
38.	Morschhauser F, Fitoussi O, Haioun CA, et al. A phase 2, multicentre, single-arm, open-label study to evaluate the safety and efficacy of single-agent lenalidomide (Revlimid^®) in subjects with relapsed or refractory peripheral T-cell non-Hodgkin lymphoma:The EXPECT trial[J].Eur J Cancer, 2013, 49(13):2869-2876.
39.	Kim SJ, Kang HJ, Kim JS, et al. PhaseⅠstudy of mTOR inhibitor everolimus plus CHOP in patients with advanced, aggressive T-cell lymphomas[J].Blood, 2011, 118(21):713-714.
40.	Foss FM, Zinzani PL, Vose JM, et al. Peripheral T-cell lymphoma[J].Blood, 2011, 117(25):6756-6767.

1. Yi SH, An G, Qi JY, et al. The significance of bone marrow involvement in aggressive lymphomas:a retrospective comparison of clinical outcomes between peripheral T cell lymphoma and diffuse large B cell lymphoma in China[J].Acta Haematol, 2010, 124(4):239-244.
2. Abouyabis AN, Shenoy PJ, Lechowicz MJ, et al. Incidence and outcomes of the peripheral T-cell lymphoma subtypes in the United States[J].Leuk Lymphoma, 2008, 49(11):2099-2107.
3. Escalón MP, Liu NS, Yang Y, et al. Prognostic factors and treatment of patients with T-cell non-Hodgkin lymphoma:the M. D. Anderson Cancer Center experience[J].Cancer, 2005, 103(10):2091-2098.
4. Jagadeesh D, Smith MR. Novel targeted therapies in peripheral T cell lymphoma[J].Discov Med, 2013, 15(85):367-378.
5. 安刚, 齐军元, 邱录贵. 外周T细胞淋巴瘤的治疗进展[J].中华血液学杂志, 2008, 29(10):718-720.
6. Gisselbrecht C, Gaulard P, Lepage E, et al. Prognostic significance of T-cell phenotype in aggressive non-Hodgkin's lymphomas. Groupe d'Etudes des Lymphomes de l'Adulte (GELA)[J].Blood, 1998, 92(1):76-82.
7. Jagadeesh D, Smith MR. Novel targeted therapies in peripheral T cell lymphoma[J].Discov Med, 2013, 15(85):367-378.
8. Gallamini A, Stelitano C, Calvi R, et al. Peripheral T-cell lymphoma unspecified (PTCL-U):a new prognostic model from a retrospective multicentric clinical study[J].Blood, 2014, 103(7):2474-2479.
9. Vose J, Armitage J, Weisenburger D, et al. International peripheral T-cell and natural killer/T-cell lymphoma study:pathology findings and clinical outcomes[J].J Clin Oncol, 2008, 26(25):4124-4130.
10. Lee J, Suh C, Park YH, et al. Extranodal natural killer T-cell lymphoma, nasal-type:a prognostic model from a retrospective multicenter study[J].J Clin Oncol, 2006, 24(4):612-618.
11. Kim SJ, Yoon DH, Jaccard A, et al. A prognostic index for natural killer cell lymphoma after non-anthracycline-based treatment:a multicenter, retrospective analysis[J].Lancet Oncol, 2016, 17(3):389-400.
12. Piccaluga PP, Agostinelli C, Righi SA, et al. Expression of CD52 in peripheral T-cell lymphoma[J].Haematologica, 2007, 92(4):566-567.
13. Rodig SJ, Abramson JS, Pinkus GS, et al. Heterogeneous CD52 expression among hematologic neoplasms:implications for the use of alemtuzumab (CAMPATH-1H)[J].Clin Cancer Res, 2006, 12(23):7174-7179.
14. Binder C, Ziepert M, Pfreundschuh M, et al. CHO(E)P-14 followed by alemtuzumab consolidation in untreated peripheral T cell lymphomas:final analysis of a prospective phase Ⅱ trial[J].Ann Hematol, 2013, 92(11):1521-1528.
15. Weidmann E, Hess G, Chow KU, et al. A phase Ⅱ study of alemtuzumab, fludarabine, cyclophosphamide, and doxorubicin (Campath-FCD) in peripheral T-cell lymphomas[J].Leuk Lymphoma, 2010, 51(3):447-455.
16. Enblad G, Hagberg H, Erlanson M, et al. A pilot study of alemtuzumab (anti-CD52 monoclonal antibody) therapy for patients with relapsed or chemotherapy-refractory peripheral T-cell lymphomas[J].Blood, 2004, 103(8):2920-2924.
17. Kim JG, Sohn SK, Chae YS, et al. Alemtuzumab plus CHOP as front-line chemotherapy for patients with peripheral T-cell lymphomas:a phase Ⅱ study[J].Cancer Chemother Pharmacol, 2007, 60(1):129-134.
18. Forero-Torres A, Leonard JP, Younes A, et al. A phase Ⅱ study of SGN-30(anti-CD30 mAb) in hodgkin lymphoma or systemic anaplastic large cell lymphoma[J].Br J Haematol, 2009, 146(2):171-179.
19. Francisco JA, Cerveny CG, Meyer DL, et al. cAC10-vcMMAE, an anti-CD30-monomethyl auristatin E conjugate with potent and selective antitumor activity[J].Blood, 2003, 102(4):1458-1465.
20. Foss FM, Sjak-Shie N, Goy A, et al. A multicenter phase Ⅱ trial to determine the safety and efficacy of combination therapy with denileukindiftitox and cyclophosphamide, doxorubicin, vincristine and prednisone in untreated peripheral T-cell lymphoma:the CONCEPT study[J].Leuk Lymphoma, 2013, 54(7):1373-1379.
21. Fanale MA, Horwitz SM, Forero-Torres A, et al. Brentuximab vedotin in the front-Line treatment of patients with CD30+ peripheral T-cell lymphomas:results of a phase Ⅰ study[J].J Clin Oncol, 2014(32):3137-3143.
22. Pro B, Advani R, Brice P, et al. Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma:results of a phase Ⅱ study[J].J Clin Oncol, 2012, 30(18):2190-2196.
23. D'Amore F, Radford J, Relander T, et al. Phase Ⅱ trial of zanolimumab (HuMax-CD4) in relapsed or refractory noncutaneous peripheral T cell lymphoma[J].Br J Haematol, 2010, 150(5):565-573.
24. Advani RH, Hong FX, Ganjoo KN, et al. Cardiac toxicity associated with the Anti-VEGF monoclonal antibody bevacizumab (avastin) in combination with CROP (A-CHOP) chemotherapy for peripheral T cell lymphoma (PTCL):the ECOG 2404 trial[J].Blood, 2009, 114(22):1671.
25. Ishida T, Ogura M, Hatake K, et al. Multicenter phase Ⅱ study of mogamulizumab (KW-0761), a defucosylated anti-CCR4 antibody, in patients with relapsed peripheral and cutaneous T-cell lymphoma[J].Blood, 2012, 120(21):795.
26. Utsunomiya A, Tobinai K, Yamamoto K, et al. Promising results of an anti-CCR4 antibody, KW-0761, for relapsed Adult T-Cell Leukemia-Lymphoma (ATL)[J].Retrovirology, 2011, 8(1):1.
27. O'connor OA, Pro B, Pinter-Brown LA, et al. Pralatrexate in patients with relapsed or refractory peripheral T-cell lymphoma:results from the pivotal PROPEL study[J].J Clin Oncol, 2011, 29(9):1182-1189.
28. Furumai R, Matsuyama A, Kobashi N, et al. FK228(depsipeptide) as a natural prodrug that inhibits class Ⅰ histone deacetylases[J].Cancer Res, 2002, 62(17):4916-4921.
29. Piekarz R, Wright J, Frye R, et al. Final results of a phase 2 NCI multicenter Study of romidepsin in patients with relapsed peripheral T-cell lymphoma (PTCL)[J].Blood, 2009, 114(22):661-662.
30. Duvic M, Kim YH, Kuzel TM, et al. The systemic effects of vorinostat in patients (Pts) with cutaneous T-cell lymphoma (CTCL):post-hoc analyses in Pts with high blood tumor burden[J].ASH Annual Meeting Abstr, 2009, 111(Abstr):1709.
31. Budde LE, Zhang MM, Shustov AR, et al. A phaseⅠstudy of pulse high-dose vorinostat (V) plus rituximab (R), ifosphamide, carboplatin, and etoposide (ICE) in patients with relapsed lymphoma[J].Br J Haematol, 2013, 161(2):183-191.
32. Foss F, Advain R, Duvic M, et al. A phase Ⅱ trial of belinostat (PXD101) in patients with relapsedor refractory peripheral or cutaneous T-cell lymphoma[J].Br J Haematol, 2015, 168(6):811-819.
33. Shi Y, Dong M, Hong X, et al. Results from a multicenter, open-label, pivotal phase Ⅱ study of chidamide in relapsed or refractory peripheral T-cell lymphoma[J].Ann Oncol, 2015, 26(8):1766-1771.
34. Kim SJ, Yoon DH, Kang HJ, et al. Bortezomib in combination with CHOP as first-line treatment for patients with stage Ⅲ/Ⅳ peripheral T-cell lymphomas:a multicentre, single-arm, phase 2 trial[J].Eur J Cancer, 2012, 48(17):3223-3231.
35. Delmer A, Fitoussi O, Gaulard P, et al. A phase Ⅱ study of bortezomib in combination with intensified CHOP-like regimen (ACVBP) in patients with previously untreated T-cell lymphoma:results of the GELA LNH05-1T trial[J].J Clin Oncol, 2009, 27(15S):8554.
36. Friedberg JW, Mahadevan D, Cebula EA, et al. Phase Ⅱ study of alisertib, a selective Aurora a kinase inhibitor, in relapsed and refractory aggressive B-and T-Cell Non-Hodgkin lymphomas[J].J Clin Oncol, 2014, 32(1):44-50.
37. Hopfinger G, Nösslinger T, Lang A, et al. Lenalidomide in combination with vorinostat and dexamethasone for the treatment of relapsed/refractory peripheral T cell lymphoma (PTCL):report of a phase Ⅰ/Ⅱ trial[J].Ann Hematol, 2014, 93(3):459-462.
38. Morschhauser F, Fitoussi O, Haioun CA, et al. A phase 2, multicentre, single-arm, open-label study to evaluate the safety and efficacy of single-agent lenalidomide (Revlimid^®) in subjects with relapsed or refractory peripheral T-cell non-Hodgkin lymphoma:The EXPECT trial[J].Eur J Cancer, 2013, 49(13):2869-2876.
39. Kim SJ, Kang HJ, Kim JS, et al. PhaseⅠstudy of mTOR inhibitor everolimus plus CHOP in patients with advanced, aggressive T-cell lymphomas[J].Blood, 2011, 118(21):713-714.
40. Foss FM, Zinzani PL, Vose JM, et al. Peripheral T-cell lymphoma[J].Blood, 2011, 117(25):6756-6767.

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外周T细胞淋巴瘤的靶向治疗进展

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