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upfront 疗法联合 CHOP 和依托泊苷在巴西结外 T 细胞淋巴瘤患者中的应用:与 CHOP 方案相比,毒性增加且无生存获益——来自中等收入国家真实世界研究的结果。

Up-front Therapy With CHOP Plus Etoposide in Brazilian nodal PTCL Patients: Increased Toxicity and No Survival Benefit Compared to CHOP Regimen-Results of a Real-Life Study From a Middle-Income Country.

机构信息

Department of Hematology, Hemotherapy & Cell Therapy, Faculty of Medicine, University of São Paulo (FMUSP), São Paulo, SP, Brazil; Laboratory of Medical Investigation in Pathogenesis and Directed Therapy in Onco-Immuno-Hematology (LIM-31), University of São Paulo (USP), São Paulo, SP, Brazil.

Department of Hematology, Hemotherapy & Cell Therapy, Faculty of Medicine, University of São Paulo (FMUSP), São Paulo, SP, Brazil.

出版信息

Clin Lymphoma Myeloma Leuk. 2022 Nov;22(11):812-824. doi: 10.1016/j.clml.2022.06.012. Epub 2022 Jun 29.

Abstract

BACKGROUND

Nodal peripheral T-cell lymphoma (nPTCL) constitute a heterogeneous group of neoplasms with aggressive behavior and poor-survival. They are more prevalent in Latin America and Asia, although data from Brazil are scarce. Its primary therapy is still controversial and ineffective. Therefore, we aim to describe clinical-epidemiological characteristics, outcomes, predictors factors for survival and compare the results of patients treated with CHOP and CHOEP regimens.

METHODS

Retrospective, observational and single-center study involving 124 nPTCL patients from Brazil treated from 2000 to 2019.

RESULTS

With a median follow-up of 23.7 months, the estimated 2-year overall survival (OS) and progression-free survival (PFS) were 59.2% and 37.3%, respectively. The median age was 48.5 years and 57.3% (71/124) were male, 81.5% (101/124) had B-symptoms, 88.7% (110/124) had advanced disease (stage III/IV) and 58.1% (72/124) presented International Prognostic Index (IPI) score ≥3, reflecting a real-life cohort. ORR to first-line therapy was 58.9%, 37.9% (N = 47) received CHOP-21 and 35.5% (N = 44) were treated with CHOEP-21; 30.1% (37/124) underwent to consolidation with involved field radiotherapy (IF-RT) and 32.3% (40/124) were consolidated with autologous hematopoietic stem cell transplantation (ASCT). The overall response rate (ORR) was similar for CHOP-21 (76.6%) and CHOEP-21 (65.9%), P = .259. Refractory disease was less frequent in the CHOEP-21 group (4.5% vs. 21.2%, P = .018). However, few patients were able to complete 6-cycles of CHOEP-21 (31.8%) than to CHOP-21 (61.7%), P = .003. Delays ≥2 weeks among the cycles of chemotherapy were more frequent for patients receiving CHOEP-21 (43.1% vs. 10.6%), P = .0004, as well as the toxicities, including G3-4 neutropenia (88% vs. 57%, P = .001), febrile neutropenia (70% vs. 38%, P = .003) and G3-4 thrombocytopenia (63% vs. 27%, P = .0007). The 2-year OS was higher for CHOP (78.7%) than CHOEP group (61.4%), P = .05, as well as 2-year PFS (69.7% vs. 25.0%, P < .0001). In multivariate analysis, high LDH (HR 3.38, P = .007) was associated with decreased OS. CR at first line (HR: 0.09, P < .001) and consolidation with ASCT (HR: 0.08, P = .015) were predictors of increased OS.

CONCLUSION

In the largest cohort of nPTCL from Latin America, patients had poor survival and high rate of chemo-resistance. In our cohort, the addition of etoposide to the CHOP-21 backbone showed no survival benefit and was associated with high-toxicity and frequent treatment interruptions. Normal LDH values, obtaintion of CR and consolidation with ASCT were independent factors associated with better outcomes.

摘要

背景

结外外周 T 细胞淋巴瘤(nPTCL)是一组具有侵袭性行为和不良预后的异质性肿瘤。它们在拉丁美洲和亚洲更为常见,尽管来自巴西的数据很少。其主要治疗方法仍存在争议且效果不佳。因此,我们旨在描述临床流行病学特征、结局、生存预测因素,并比较接受 CHOP 和 CHOEP 方案治疗的患者的结果。

方法

回顾性、观察性和单中心研究,纳入了 2000 年至 2019 年期间在巴西接受治疗的 124 例 nPTCL 患者。

结果

中位随访 23.7 个月,估计 2 年总生存率(OS)和无进展生存率(PFS)分别为 59.2%和 37.3%。中位年龄为 48.5 岁,57.3%(71/124)为男性,81.5%(101/124)有 B 症状,88.7%(110/124)为晚期疾病(III/IV 期),58.1%(72/124)的国际预后指数(IPI)评分≥3,反映了真实世界的队列。一线治疗的客观缓解率(ORR)为 58.9%,37.9%(N=47)接受 CHOP-21 治疗,35.5%(N=44)接受 CHOEP-21 治疗;30.1%(37/124)接受累及野放疗(IF-RT)巩固治疗,32.3%(40/124)接受自体造血干细胞移植(ASCT)巩固治疗。CHOP-21(76.6%)和 CHOEP-21(65.9%)的 ORR 相似,P=0.259。难治性疾病在 CHOEP-21 组较少见(4.5% vs. 21.2%,P=0.018)。然而,接受 CHOEP-21 治疗的患者完成 6 个周期的比例(31.8%)明显低于接受 CHOP-21 治疗的患者(61.7%),P=0.003。化疗周期中≥2 周的延迟在接受 CHOEP-21 治疗的患者中更为常见(43.1% vs. 10.6%,P=0.0004),毒性包括 3-4 级中性粒细胞减少症(88% vs. 57%,P=0.001)、发热性中性粒细胞减少症(70% vs. 38%,P=0.003)和 3-4 级血小板减少症(63% vs. 27%,P=0.0007)。CHOP 组(78.7%)的 2 年 OS 高于 CHOEP 组(61.4%),P=0.05,2 年 PFS(69.7% vs. 25.0%)也更高,P<0.0001。多变量分析显示,高乳酸脱氢酶(HR 3.38,P=0.007)与 OS 降低相关。一线治疗获得完全缓解(HR:0.09,P<0.001)和接受 ASCT 巩固治疗(HR:0.08,P=0.015)是 OS 改善的预测因素。

结论

在拉丁美洲最大的 nPTCL 队列中,患者的生存较差且化疗耐药率较高。在我们的队列中,依托泊苷联合 CHOP-21 方案并未带来生存获益,且与高毒性和频繁治疗中断相关。正常的 LDH 值、获得完全缓解和接受 ASCT 巩固治疗是与更好结局相关的独立因素。

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