苯达莫司汀联合R-CHOP方案对弥漫大B细胞淋巴瘤疗效及安全性的影响

刘亚宁; 李焱; 任利涛; 侯小雪; 王茜

doi:10.16766/j.cnki.issn.1674-4152.003587

苯达莫司汀联合R-CHOP方案对弥漫大B细胞淋巴瘤疗效及安全性的影响

doi: 10.16766/j.cnki.issn.1674-4152.003587

刘亚宁¹,
李焱^1, ,,
任利涛²,
侯小雪³,
王茜⁴

1.
邯郸市第一医院血液内科，河北邯郸 056002
2.
邯郸市第一医院医务科
3.
邯郸市第一医院重症医学科
4.
河北医科大学第二医院血液内科，河北石家庄 050004

基金项目:

河北省2023年度医学科学研究项目 20231188

详细信息

通讯作者:
李焱，E-mail：handanliyan68@sohu.com

中图分类号: R733.4 R730.53
计量
- 文章访问数: 19
- HTML全文浏览量: 13
- PDF下载量: 3
- 被引次数: 0
出版历程
- 收稿日期: 2023-12-14
- 网络出版日期: 2024-09-05

Effects of bendamustine combined with R-CHOP on the efficacy and safety of diffuse large B-cell lymphoma

1.
Department of Hematology, Handan First Hospital, Handan, Hebei 056002, China

摘要

摘要: 目的探究苯达莫司汀(BEN)联合利妥昔单抗+CHOP(R-CHOP)方案对弥漫大B细胞淋巴瘤(DLBCL)疗效、血清因子及不良反应的影响。方法选取2018年1月—2020年6月期间邯郸市第一医院收治的140例DLBCL患者，根据随机数字表法分为2组，分别采用R-CHOP方案(对照组, 70例)和BEN联合R-CHOP方案治疗(观察组, 70例)，比较2组疗效及安全性。结果观察组客观缓解率(ORR)高于对照组[85.71%(60/70) vs. 71.43%(50/70)，χ²=4.242，P < 0.05)；治疗后观察组糖类抗原125(CA125)、乳酸脱氢酶(LDH)、血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)、核转录因-κB p50(NF-κB p50)均低于对照组[(18.34±2.75)U/L vs. (22.54±3.11)U/L，(227.16±35.12)U/L vs. (282.71±37.46)U/L，(75.08±10.76)ng/L vs. (81.29±12.41)ng/L，(17.29±1.81)ng/L vs. (19.16±2.07)ng/L，(976.58±104.08)μg/L vs. (1 137.19±197.65)μg/L，P < 0.05]。2组治疗期间各不良反应发生率差异均无统计学意义(P>0.05)。观察组累计生存率及累计无进展生存率高于对照组(log-rank χ²=4.243、3.959，P=0.039、0.047)。结论 BEN联合R-CHOP方案能提高DLBCL患者的近远期疗效，改善血清指标，安全有效。
- 弥漫大B细胞淋巴瘤 /
- 苯达莫司汀 /
- R-CHOP方案 /
- 疗效 /
- 不良反应
Abstract: Objective To investigate the effects of bendamustine (BEN) combined with rituximab+cyclophosphamide, doxorubicin, vincristine, methylprednisolone (R-CHOP) regimen on the efficacy, serum factors, and adverse reactions in patients with diffuse large B-cell lymphoma (DLBCL). Methods A total of 140 DLBCL patients at Handan First Hospital from January 2018 to June 2020 were selected. Using a random number table, they were divided into 2 groups: the control group receiving R-CHOP and the observation group receiving BEN combined with R-CHOP. Their efficacy and safety of the two groups were then compared. Results The objective response rate (ORR) of the observation group was higher than that of the control group [85.71% (60/70) vs. 71.43% (50/70), χ²=4.242, P < 0.05]. Post-treatment, levels of carbohydrate antigen 125 (CA125), lactate dehydrogenase (LDH), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and nuclear transcription face-κB p50 (NF-κB p50) in the observation group were lower than those in the control group [(18.34±2.75) U/L vs. (22.54±3.11) U/L, (227.16±35.12) U/L vs. (282.71±37.46) U/L, (75.08±10.76) ng/L vs. (81.29±12.41) ng/L, (17.29±1.81) ng/L vs. (19.16±2.07) ng/L, (976.58±104.08) μg/L vs. (1 137.19±197.65) μg/L, P < 0.05]. There was no significant difference in the incidence of adverse reactions between the two groups during treatment (P>0.05). Furthermore, the cumulative survival rate and progression-free survival rate in the observation group were higher than those in the control group (log-rank χ²=4.243, 3.959, P=0.039, 0.047, respectively). Conclusion Combining BEN with R-CHOP improves the short-term and long-term efficacy of DLBCL patients, enhances serum indexes, and ensures safety and effectiveness.
- Diffuse large B-cell lymphoma /
- Bendamustine /
- R-CHOP protocol /
- Curative effect /
- Adverse reaction

HTML全文

图 1 2组DLBCL患者生存曲线

Figure 1. Survival curves of DLBCL patients in two groups

下载: 全尺寸图片幻灯片

图 2 2组DLBCL患者无进展生存曲线

Figure 2. Progression-free survival curves of DLBCL patients in two groups

下载: 全尺寸图片幻灯片

表 1 2组DLBCL患者一般资料比较

Table 1. Comparison of general data between two groups of DLBCL patients

组别	例数	性别[例(%)]		年龄 (x±s, 岁)	分期[例(%)]			国际预后指数[例(%)]
组别	例数	男性	女性	年龄 (x±s, 岁)	Ⅰ期	Ⅱ期	Ⅲ期	低危~低中危	高中危~高危
观察组	70	37(52.86)	33(47.14)	49.71±4.12	21(30.00)	30(42.86)	19(27.14)	41(58.57)	29(41.13)
对照组	70	41(58.57)	29(41.43)	48.94±4.31	18(25.71)	27(38.57)	25(35.71)	38(54.29)	32(45.71)
统计量		0.463^a		1.082^b	1.207^a			0.261^a
P值		0.496		0.281	0.547			0.609
注：^a为χ²值，^b为t值。

下载: 导出CSV

表 2 2组DLBCL患者临床疗效比较[例(%)]

Table 2. Comparison of clinical efficacy between two groups of DLBCL patients[case (%)]

组别	例数	CR	PR	SD	PD	ORR
对照组	70	37(52.86)	13(18.57)	11(15.71)	9(12.86)	50(71.43)
观察组	70	40(57.14)	20(28.57)	7(10.00)	3(4.29)	60(85.71)
注：2组ORR比较，χ²=4.242，P=0.039。

下载: 导出CSV

表 3 2组DLBCL患者血清指标比较(x±s)

Table 3. Comparison of serum indexes between two groups of DLBCL patients (x±s)

组别	例数	CA125(U/L)		LDH(U/L)		VEGH(ng/L)		bFGF(ng/L)		NF-κB p50(μg/L)
组别	例数	治疗前	治疗后	治疗前	治疗后	治疗前	治疗后	治疗前	治疗后	治疗前	治疗后
对照组	70	38.55±5.91	22.54±3.11^b	352.46±69.54	282.71±37.46^b	147.33±15.95	81.29±12.41^b	26.95±2.56	19.16±2.07^b	1 590.26±229.41	1 137.19±197.65^b
观察组	70	39.13±6.24	18.34±2.75^b	349.71±65.26	227.16±35.12^b	145.96±17.54	75.08±10.76^b	27.33±2.43	17.29±1.81^b	1 603.51±267.57	976.58±104.08^b
统计量		0.555^a	7.864^c	0.241^a	8.693^c	0.487^a	3.064^c	0.877^a	5.139^c	0.314^a	6.271^c
P值		0.580	< 0.001	0.810	< 0.001	0.627	< 0.001	0.382	< 0.001	0.754	< 0.001
注：^a为t值，^c为F值；与治疗前比较，^bP < 0.05。

下载: 导出CSV

表 4 2组DLBCL患者Ⅲ级及以上药物不良反应发生率比较[例(%)]

Table 4. Comparison of Grade Ⅲ and above adverse drug reactions between two groups of DLBCL patients[case (%)]

组别	例数	恶心呕吐	白细胞减少	血小板减少	腹泻	肾功能异常
对照组	70	7(10.00)	5(7.14)	5(7.14)	3(4.29)	1(1.43)
观察组	70	10(14.29)	6(8.57)	4(5.71)	4(5.71)	3(4.29)
χ²值		0.603	0.099	< 0.001	< 0.001	0.257
P值		0.438	0.753	0.999	0.999	0.612

下载: 导出CSV

参考文献(21)

[1]	HE M Y, KRIDEL R. Treatment resistance in diffuse large B-cell lymphoma[J]. Leukemia, 2021, 35(8): 2151-2165. doi: 10.1038/s41375-021-01285-3
[2]	WRIGHT G W, HUANG D W, PHELAN J D, et al. A probabilistic classification tool for genetic subtypes of diffuse large B cell lymphoma with therapeutic implications[J]. Cancer Cell, 2020, 37(4): 551-568. e14. doi: 10.1016/j.ccell.2020.03.015
[3]	POLETTO S, NOVO M, PARUZZO L, et al. Treatment strategies for patients with diffuse large B-cell lymphoma[J]. Cancer Treat Rev, 2022, 110: 102443. DOI: 10.1016/j.ctrv.2022.102443.
[4]	郭佳丽, 潘晨华, 李依, 等. 弥漫大B细胞淋巴瘤预后相关基因与患者预后及肿瘤浸润性免疫细胞比例的相关性[J]. 山东医药, 2023, 63(3): 33-36. doi: 10.3969/j.issn.1002-266X.2023.03.007 GUO J L, PAN C H, LI Y, et al. Correlation of independent prognosis-related genes in diffuse large B-cell lymphoma with patients'prognosis and proportion of tumour-infiltrating immune cells[J]. Shandong Medical Journal, 2023, 63(3): 33-36. doi: 10.3969/j.issn.1002-266X.2023.03.007
[5]	WANG L, LI L R, YOUNG K H. New agents and regimens for diffuse large B cell lymphoma[J]. J Hematol Oncol, 2020, 13(1): 175. DOI: 10.1186/s13045-020-01011-z.
[6]	石磊, 陆敏秋, 高珊, 等. 苯达莫司汀联合化疗方案治疗复发/难治性多发性骨髓瘤的临床观察[J]. 中国医师杂志, 2021, 23(12): 1822-1827. doi: 10.3760/cma.j.cn431274-20210702-00719 SHI L, LU M Q, GAO S, et al. Clinical reasearch of bendamustine combination regimen in the treatment of relapsed/refractory multiple myeloma[J]. Journal of Chinese Physician, 2021, 23(12): 1822-1827. doi: 10.3760/cma.j.cn431274-20210702-00719
[7]	蓝晓凤, 贤晓敏, 刘玄勇, 等. 苯达莫司汀治疗边缘区淋巴瘤的单中心回顾性研究[J]. 中南药学, 2022, 20(7): 1510-1514. https://www.cnki.com.cn/Article/CJFDTOTAL-ZNYX202207006.htm LAN X F, XIAN X M, LIU X Y, et al. Efficacy and safety of bendamustine for patients with marginal zone lymphoma: a single center retrospective study[J]. Central South Pharmacy, 2022, 20(7): 1510-1514. https://www.cnki.com.cn/Article/CJFDTOTAL-ZNYX202207006.htm
[8]	GHILARDI G, CHONG E A, SVOBODA J, et al. Bendamustine is safe and effective for lymphodepletion before tisagenlecleucel in patients with refractory or relapsed large B-cell lymphomas[J]. Ann Oncol, 2022, 33(9): 916-928. doi: 10.1016/j.annonc.2022.05.521
[9]	中华医学会血液学分会, 中国抗癌协会淋巴瘤专业委员会. 中国弥漫大B细胞淋巴瘤诊断与治疗指南(2013年版)[J]. 中华血液学杂志, 2013, 34(9): 816-819. Hematology Branch of Chinese Medical Association, Lymphoma Professional Committee of Chinese Anticancer Association. Chinese guidelines for diagnosis and treatment of difuse large B cell lymphoma (2013)[J]. Chinese Journal of Hematology, 2013, 34(9): 816-819.
[10]	MISCHEL A M, ROSIELLE D A. Eastern Cooperative Oncology Group performance status #434[J]. J Palliat Med, 2022, 25(3): 508-510. doi: 10.1089/jpm.2021.0599
[11]	ARAS M, ERDIL T Y, DANE F, et al. Comparison of WHO, RECIST 1.1, EORTC, and PERCIST criteria in the evaluation of treatment response in malignant solid tumors[J]. Nucl Med Commun, 2016, 37(1): 9-15. doi: 10.1097/MNM.0000000000000401
[12]	张贵兵, 何正飞, 商文忠, 等. 三乙醇胺对弥漫大B细胞淋巴瘤细胞生物特性的影响[J]. 中华全科医学, 2022, 20(5): 785-788. doi: 10.16766/j.cnki.issn.1674-4152.002454 ZHANG G B, HE Z F, SHANG W Z, et al. Effect of triethanolamine on the biological characteristics of diffuse large B-cell lymphoma cells[J]. Chinese Journal of General Practice, 2022, 20(5): 785-788. doi: 10.16766/j.cnki.issn.1674-4152.002454
[13]	SONG Y, ZHOU H, ZHANG H, et al. Efficacy and safety of the biosimilar IBI301 plus standard CHOP (I-CHOP) in comparison with rituximab plus CHOP (R-CHOP) in patients with previously untreated diffuse large B-Cell lymphoma (DLBCL): a randomized, double-blind, parallel-group, phase 3 trial[J]. Adv Ther, 2021, 38(4): 1889-1903. doi: 10.1007/s12325-020-01603-8
[14]	LALIC H, AURER I, BATINIC D, et al. Bendamustine: a review of pharmacology, clinical use and immunological effects (review)[J]. Oncol Rep, 2022, 47(6): 114. DOI: 10.3892/or.2022.8325.
[15]	崔玉山, 房佰俊. 苯达莫司汀/马法兰预处理方案可提高接受移植的多发性骨髓瘤患者完全缓解率[J]. 中华医学杂志, 2022, 102(36): 2880. CUI Y S, FANG B J. Bendamustine/mafaran preconditioning regimen can improve the complete response rate of multiple myeloma patients receiving transplantation[J]. National Medical Journal of China, 2022, 102(36): 2880.
[16]	GERRITY C, MERCADEL A, ALGHAMDI A, et al. Primary ovarian lymphoma: a case report[J]. Gynecol Oncol Rep, 2023, 47: 101212. DOI: 10.1016/j.gore.2023.101212.
[17]	SHEN N, YU Y, ZHANG R, et al. Expression and prognostic value of PIK3CA, VEGF, IL-8, IL-10, and RIP2 in diffuse large B-cell lymphoma[J]. Int J Clin Pract, 2022: 2637581. DOI: 10.1155/2022/2637581.
[18]	HARTERT K T, WENZL K, KRULL J E, et al. Targeting of inflammatory pathways with R2CHOP in high-risk DLBCL[J]. Leukemia, 2021, 35(2): 522-533. doi: 10.1038/s41375-020-0766-4
[19]	安立才, 刘英慧, 王婧瑶, 等. 含苯达莫司汀预处理方案自体造血干细胞移植治疗淋巴瘤的近期疗效及安全性[J]. 中华血液学杂志, 2022, 43(1): 63-65. https://www.cnki.com.cn/Article/CJFDTOTAL-XYSY202304016.htm AN L C, LIU Y H, WANG J Y, et al. Safety and the short-term efficacy of bendamustine in the conditioning regimen for autologous stem cell transplantation in patients with lymphoma[J]. Chinese Journal of Hematology, 2022, 43(1): 63-65. https://www.cnki.com.cn/Article/CJFDTOTAL-XYSY202304016.htm
[20]	熊行芳, 谢晓丽, 王志强, 等. 青蒿琥酯联合苯达莫司汀对弥漫大B细胞淋巴瘤增殖和凋亡的影响[J]. 中国临床药理学杂志, 2023, 39(5): 669-673. https://www.cnki.com.cn/Article/CJFDTOTAL-GLYZ202305013.htm XIONG X F, XIE X L, WANG Z Q, et al. Effects of artesunate combined with bendamustine on proliferation and apoptosis of diffuse large B cell lymphoma[J]. The Chinese Journal of Clinical Pharmacology, 2023, 39(5): 669-673. https://www.cnki.com.cn/Article/CJFDTOTAL-GLYZ202305013.htm
[21]	杜超, 卓秋琪, 罗舟, 等. 苯达莫司汀的药理机制及药动学研究进展[J]. 河北医药, 2021, 43(12): 1883-1888. doi: 10.3969/j.issn.1002-7386.2021.12.031 DU C, ZHUO Q Q, LUO Z, et al. Research progress on the pharmacological mechanism and pharmacokinetics of bendamustine[J]. Hebei Medical Journal, 2021, 43(12): 1883-1888. doi: 10.3969/j.issn.1002-7386.2021.12.031