DA-EPOCH方案联合或不联合利妥昔单抗治疗年轻人初治中危至高危弥漫大B细胞淋巴瘤临床研究

Clinical study of DA-EPOCH regimen combined with or without rituximab in treatment of young newly diagnosed patients with middle and high-risk diffuse large B-cell lymphoma

目的 观察DA-EPOCH方案联合或不联合利妥昔单抗治疗年轻人初治中危至高危弥漫大B细胞淋巴瘤(DLBCL)的临床疗效及预后.方法 回顾性分析贵州省肿瘤医院2014年11月至2018年12月107例年轻、中至高危、予DA-EPOCH方案联合或不联合利妥昔单抗初治的DLBCL患者临床资料,根据是否使用利妥昔单抗分为R-DA-EPOCH组(65例)和DA-EPOCH组(42例);根据化疗后是否进行受累野放疗(IFRT)对99例具有放疗指征者分组,其中行IFRT组59例,未行IFRT组40例,对组间进行疗效分析.结果 全组总有效率(ORR)86.0%(92/107),1、2年总生存(OS)率分别为90.6%和75.3%,1、2年无进展生存(PFS)率为79.1%和56.5%. R-DA-EPOCH组ORR[87.7%(57/65)比83.3% (35/42)],1、2年OS率(94.8%比84.9%、80.4%比68.2%)及1、2年PFS率(90.5%比77.0%、61.0%比50.8%)均高于DA-EPOCH组,但差异均无统计学意义(均P>0.05).行IFRT组与未行IFRT组ORR分别为98.2% (56/57)和80.0%(32/40)(χ2=7.225,P=0.007),2年OS率分别为86.0%和63.3% (P<0.05);放疗所致的不良反应主要为Ⅰ~Ⅱ级局部皮肤黏膜反应[42.4%(25/59)].多因素分析结果显示,治疗后清蛋白值是影响患者OS的独立预后因素(95% CI 2.709~21.433, P<0.01);而影响患者PFS率的独立预后因素为性别(95% CI 0.020~0.318, P<0.01)、治疗后清蛋白水平(95% CI 2.097~12.219, P<0.01)、治疗后β2微球蛋白水平(95% CI 0.080~0.602, P<0.01)和治疗后淋巴细胞绝对值/单核细胞绝对值(95% CI 0.113~0.720, P<0.01).结论 年轻、初治、中危至高危DLBCL具有高度异质性,利妥昔单抗联合DA-EPOCH方案化疗可提高患者疗效,化疗后予IFRT可提高患者的近期疗效及OS率,不良反应可耐受.

Objective To observe the clinical efficacy and prognosis of DA-EPOCH regimen combined with or without rituximab [(R)-DA-EPOCH regimen] in treatment of young newly diagnosed patients with middle and high-risk diffuse large B-cell lymphoma (DLBCL). Methods The clinical data of 107 young newly diagnosed middle to high-risk DLBCL patients treated with (R)-DA-EPOCH regimen at Guizhou Cancer Hospital between November 2014 and December 2018 were retrospectively analyzed. The efficacies were analyzed by grouping according to rituximab (65 cases in R-DA-EPOCH group and 42 cases in DA-EPOCH group), and according to involved-filed radiotherapy (IFRT) after chemotherapy (99 cases with chemotherapy indications including 59 cases with IFRT and 40 cases without IFRT). Results The objective response rate (ORR) was 86.0% (92/107). The 1-, 2-year overall survival (OS) rate was 90.6% and 75.3%. The 1-, 2-year progression-free survival (PFS) rate was 79.1% and 56.5%. The ORR, 1-year OS rate, 2-year OS rate, 1-year PFS rate and 2-year PFS rate in R-DA-EPOCH group were higher than those in DA-EPOCH group [87.7% (57/65) vs. 83.3% (35/42), 94.8% vs. 84.9% , 80.4% vs. 68.2% , 90.5% vs. 77.0% , 61.0% vs. 50.8% , respectively), but there were no statistical differences (all P > 0.05). The ORR of IFRT group and non-IFRT group was 98.2% (56/57) and 80.0% (32/40) (χ 2 = 7.225, P= 0.007). The 2-year OS rate was 86.0% and 63.3% (P<0.05). Main adverse reactions caused by radiotherapy were local skin mucosa reactions of gradeⅠ-Ⅱ [42.4% (25/59)]. Multivariate analysis showed that albumin value after treatment was an independent prognosis factor affecting OS rate (95% CI 2.709-21.433, P<0.01). Gender (95% CI 0.020-0.318, P<0.01), albumin level (95% CI 2.097-12.219, P< 0.01), Beta 2 microglobulin level (95% CI 0.080-0.602, P< 0.01) and absolute lymphocyte count/absolute monocyte count (95% CI 0.113-0.720, P< 0.01) after treatment were independent prognosis factors affecting PFS rate. Conclusions The young newly diagnosed patients with middle and high-risk DLBCL are highly heterogeneous. Rituximab combined with DA-EPOCH regimen can improve the efficacy of patients. IFRT after chemotherapy may increase the short-term efficacy and OS, and the adverse reactions are tolerant.