R-EPOCH在初治MYC/Bcl-2双表达弥漫大B细胞淋巴瘤患者的疗效分析
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摘要
目的:评估R-EPOCH在初治MYC/Bcl-2双表达弥漫大B细胞淋巴瘤患者的有效性及安全性。方法:回顾性分析22例接受R-EPOCH方案初治MYC/Bcl-2双表达弥漫大B细胞淋巴瘤患者,排除其中双重或三重打击淋巴瘤,分析患者疗效、安全性及预后情况。结果:22例患者中17例(77.3%)获得完全缓解,总体有效率达86.4%(19/22)。采用R-EPOCH方案治疗1年总生存率(OS)和无进展生存率(PFS)分别为90.4%和74.7%。单因素分析表明,IPI评分低危的MYC/Bcl-2双表达患者的PFS优于IPI评分高危患者(P=0.080,HR 5.013,95%CI 0.82～30.55)。女性患者的OS显著差于男性(P=0.036)。不良反应分析结果显示,患者3～4级白细胞降低发生率为90.9%(20/22),3～4级血小板减少症发生率为72.7%(16/22),余不良反应均较轻微,所有患者经对症治疗后,均顺利完成治疗。结论:R-EPOCH治疗MYC/Bcl-2双重表达淋巴瘤患者安全、有效,虽然存在血液毒性等不良反应,但多数患者可以耐受。综合考虑R-EPOCH是目前治疗双表达淋巴瘤较为理想的治疗方案,但仍需要进行前瞻性的随机比较。
Objective:To evaluate the efficacy and safety of R-EPOCH in the treatment of the newly diagnosed diffuse large B-cell lymphoma with dual-expression of MYC/Bcl-2.Method:A retrospective analysis of 22 diffuse large B-cell lymphoma patients with dual expression who received R-EPOCH was performed,and all patients with dual or triple-hit lymphoma were excluded.The efficacy,adverse events and prognosis were analyzed.Result:Of the 22 patients,17 cases(77.3%) achieved complete remission and the overall effective rate was 86.4%(19/22).The 1-year overall survival(OS) rate and progression-free survival(PFS) rate of patients treated with R-EPOCH were 90.4% and 74.7%,respectively.Univariate analysis showed that PFS with low-risk IPI patients was superior to high-risk patients(P=0.080,HR 5.013,95%CI 0.82-30.55).The OS of female patients was significantly lower than that of male patients(P=0.036).The adverse events analysis showed that the incidence of grade 3-4 leukopenia in 22 patients was 90.9%(20/22),and that of grade 3-4 thrombocytopenia was 72.7%(16/22).The residual adverse events were mild.All patients were successfully treated after symptomatic treatment.Conclusion:R-EPOCH is an effective and safe treatment for patients with MYC/Bcl-2 double express lymphoma.Although there are adverse events such as hematological toxicity,most patients are tolerable.Considering that R-EPOCH is currently an ideal treatment for the treatment of double-express lymphoma,a prospective random comparison is still needed.
Objective:To evaluate the efficacy and safety of R-EPOCH in the treatment of the newly diagnosed diffuse large B-cell lymphoma with dual-expression of MYC/Bcl-2.Method:A retrospective analysis of 22 diffuse large B-cell lymphoma patients with dual expression who received R-EPOCH was performed,and all patients with dual or triple-hit lymphoma were excluded.The efficacy,adverse events and prognosis were analyzed.Result:Of the 22 patients,17 cases(77.3%) achieved complete remission and the overall effective rate was 86.4%(19/22).The 1-year overall survival(OS) rate and progression-free survival(PFS) rate of patients treated with R-EPOCH were 90.4% and 74.7%,respectively.Univariate analysis showed that PFS with low-risk IPI patients was superior to high-risk patients(P=0.080,HR 5.013,95%CI 0.82-30.55).The OS of female patients was significantly lower than that of male patients(P=0.036).The adverse events analysis showed that the incidence of grade 3-4 leukopenia in 22 patients was 90.9%(20/22),and that of grade 3-4 thrombocytopenia was 72.7%(16/22).The residual adverse events were mild.All patients were successfully treated after symptomatic treatment.Conclusion:R-EPOCH is an effective and safe treatment for patients with MYC/Bcl-2 double express lymphoma.Although there are adverse events such as hematological toxicity,most patients are tolerable.Considering that R-EPOCH is currently an ideal treatment for the treatment of double-express lymphoma,a prospective random comparison is still needed.
引文
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[7] Hans CP,Weisenburger DD,Greiner TC,et al.Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray[J].Blood,2004,103:275-282.
[8] Cheson BD,Pfistner B,Juweid ME,et al.Revised response criteria for malignant lymphoma[J].J Clin Oncol,2007,25:579-586.
[9] Trotti A,Colevas AD,Setser A,et al.CTCAE v3.0:development of a comprehensive grading system for the adverse effects of cancer treatment[J].Semin Radiat Oncol,2003,13:176-181.
[10] Dunleavy K,Fanale MA,Abramson JS,et al.Dose-adjusted EPOCH-R (etoposide,prednisone,vincristine,cyclophosphamide,doxorubicin,and rituximab) in untreated aggressive diffuse large B-cell lymphoma with MYC rearrangement:a prospective,multicentre,single-arm phase 2 study[J].Lancet Haematol,2018,5:e609-e617.
[11] Swerdlow SH,Campo E,Pileri SA,et al.The 2016 revision of the World Health Organization classification of lymphoid neoplasms[J].Blood,2016,127:2375-2390.
[12] Johnson NA,Slack GW,Savage KJ,et al.Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide,doxorubicin,vincristine,and prednisone[J].J Clin Oncol,2012,30:3452-3459.
[13] Horn H,Ziepert M,Becher C,et al.MYC status in concert with Bcl-2 and BCL6 expression predicts outcome in diffuse large B-cell lymphoma[J].Blood,2013,121:2253-2263.
[14] Friedberg JW.How I treat double-hit lymphoma[J].Blood,2017,130:590-596.
[15] Aggarwal HR,Alakeel F,Finianos AN,et al.Outcome of patients with double-expressor lymphomas (DELs) treated with R-CHOP or R-(DA)EPOCH[J].Blood.2016,128:5396.
[16] Dodero A,Guidetti A,Tucci A,et al.Dose-adjusted EPOCH plus rituximab improves the clinical outcome of young patients affected by double expressor diffuse large B-cell lymphoma[J].Leukemia,2019,33:1047-1051.
[17] Leslie LA,Kothadia S,Protomastro E,et al.Treatment of high risk DLBCL with DA-R-(DA)EPOCH in those unable to tolerate intensive chemotherapy:well-tolerated and effective,but inadequate in double/triple hit or expressing DLBCL[J].Blood,2017,130(Suppl 1):4163.
[18] Zhang XY,Liang JH,Wang L,et al.DA-EPOCH-R improves the outcome over that of R-CHOP regimen for DLBCL patients below 60 years,GCB phenotype,and those with high-risk IPI,but not for double expressor lymphoma[J].J Cancer Res Clin Oncol,2019,145:117-127.
[19] Bhagirathbhai D,Prakash V,Yenni A.Clinical outcomes and cost analysis of dose-adjusted R-EPOCH vs R-CHOP in treatment of diffuse large B-cell lymphoma with high risk features[J].Blood,2018,132(Suppl 1):4790.
[2] Swerdlow SH,Campo E,Pileri SA,et al.The 2016 revision of the World Health Organization (WHO) classification of lymphoid neoplasms[J].Blood,2016,127:2375-2390.
[3] Clark Schneider KM,Banks PM,Collie AM,et al.Dual expression of MYC and BCL2 proteins predicts worse outcomes in diffuse large B-cell lymphoma[J].Leuk Lymphoma,2016,57:1640-1648.
[4] Wilson WH,Sin-Ho J,Pierluigi P,et al.A Cancer and Leukemia Group B multi-center study of DA-EPOCH-rituximab in untreated diffuse large B-cell lymphoma with analysis of outcome by molecular subtype[J].Haematologica,2012,97:758-765.
[5] Oki Y,Noorani M,Lin P,et al.Double hit lymphoma:the MD Anderson Cancer Center clinical experience[J].Br J Haematol,2014,166:891-901.
[6] Gutierrez M,Chabner BA,Pearson D,et al.Role of a doxorubicin-containing regimen in relapsed and resistant lymphomas:an 8-year follow-up study of EPOCH[J].J Clin Oncol,2000,18:3633-3642.
[7] Hans CP,Weisenburger DD,Greiner TC,et al.Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray[J].Blood,2004,103:275-282.
[8] Cheson BD,Pfistner B,Juweid ME,et al.Revised response criteria for malignant lymphoma[J].J Clin Oncol,2007,25:579-586.
[9] Trotti A,Colevas AD,Setser A,et al.CTCAE v3.0:development of a comprehensive grading system for the adverse effects of cancer treatment[J].Semin Radiat Oncol,2003,13:176-181.
[10] Dunleavy K,Fanale MA,Abramson JS,et al.Dose-adjusted EPOCH-R (etoposide,prednisone,vincristine,cyclophosphamide,doxorubicin,and rituximab) in untreated aggressive diffuse large B-cell lymphoma with MYC rearrangement:a prospective,multicentre,single-arm phase 2 study[J].Lancet Haematol,2018,5:e609-e617.
[11] Swerdlow SH,Campo E,Pileri SA,et al.The 2016 revision of the World Health Organization classification of lymphoid neoplasms[J].Blood,2016,127:2375-2390.
[12] Johnson NA,Slack GW,Savage KJ,et al.Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide,doxorubicin,vincristine,and prednisone[J].J Clin Oncol,2012,30:3452-3459.
[13] Horn H,Ziepert M,Becher C,et al.MYC status in concert with Bcl-2 and BCL6 expression predicts outcome in diffuse large B-cell lymphoma[J].Blood,2013,121:2253-2263.
[14] Friedberg JW.How I treat double-hit lymphoma[J].Blood,2017,130:590-596.
[15] Aggarwal HR,Alakeel F,Finianos AN,et al.Outcome of patients with double-expressor lymphomas (DELs) treated with R-CHOP or R-(DA)EPOCH[J].Blood.2016,128:5396.
[16] Dodero A,Guidetti A,Tucci A,et al.Dose-adjusted EPOCH plus rituximab improves the clinical outcome of young patients affected by double expressor diffuse large B-cell lymphoma[J].Leukemia,2019,33:1047-1051.
[17] Leslie LA,Kothadia S,Protomastro E,et al.Treatment of high risk DLBCL with DA-R-(DA)EPOCH in those unable to tolerate intensive chemotherapy:well-tolerated and effective,but inadequate in double/triple hit or expressing DLBCL[J].Blood,2017,130(Suppl 1):4163.
[18] Zhang XY,Liang JH,Wang L,et al.DA-EPOCH-R improves the outcome over that of R-CHOP regimen for DLBCL patients below 60 years,GCB phenotype,and those with high-risk IPI,but not for double expressor lymphoma[J].J Cancer Res Clin Oncol,2019,145:117-127.
[19] Bhagirathbhai D,Prakash V,Yenni A.Clinical outcomes and cost analysis of dose-adjusted R-EPOCH vs R-CHOP in treatment of diffuse large B-cell lymphoma with high risk features[J].Blood,2018,132(Suppl 1):4790.