达雷妥尤单抗在多发性骨髓瘤中的应用

贺玉钦; 陈文明

doi:10.13201/j.issn.1004-2806.2023.07.002

达雷妥尤单抗在多发性骨髓瘤中的应用

贺玉钦¹,
陈文明^1, ,

- 首都医科大学附属北京朝阳医院(北京，100020)
基金项目:
“重大新药创制”科技重大专项(No: 2018ZX09733003)

详细信息

作者简介:
陈文明，主任医师，教授，博士研究生导师。首都医科大学附属北京朝阳医院血液科主任，北京市多发性骨髓瘤医疗研究中心主任以及首都医科大学血液病学系主任；北京市医管局登峰人才团队及多发性骨髓瘤重点专业带头人；国际骨髓瘤工作组(IMWG)委员、亚洲骨髓瘤网(AMN)常委；中国医药教育协会常务理事、血液学专业委员会主任委员；北京大众健康科普促进会副会长；中华医学会血液分会浆细胞学组副组长。先后获国家科技重大专项2项、国家自然科学基金、北京市自然科学基金等10余项资助，发表学术论文300余篇

通讯作者: 陈文明，E-mail：13910107759@163.com

中图分类号: R733.3

收稿日期: 2023-05-22

刊出日期: 2023-07-01

Application of daratumumab in multiple myeloma

HE Yuqin¹,
CHEN Wenming^1, ,

- Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China

More Information

Corresponding author: CHEN Wenming, E-mail: 13910107759@163.com

Received Date: 22 May 2023

Publish Date: 01 July 2023

摘要

摘要: 达雷妥尤单抗是一种新型人源化抗CD38单克隆抗体，可靶向治疗多发性骨髓瘤(multiple myeloma，MM)瘤细胞表面的CD38，直接杀伤肿瘤细胞和通过调节免疫微环境双重作用机制发挥抗骨髓瘤作用。多项大型临床证实含达雷妥尤单抗联合方案不仅可用于新诊断MM患者的诱导、巩固治疗，也可作为复发/难治性MM患者的治疗选择，并在维持治疗阶段显示出良好的疗效与耐受性。真实世界研究进一步验证含达雷妥尤单抗的方案在MM患者中的疗效。文章基于已有的循证医学证据，重点介绍达雷妥尤单抗在MM中的临床应用。
- 达雷妥尤单抗 /
- 多发性骨髓瘤 /
- 新诊断 /
- 复发或难治 /
- 维持治疗
Abstract: Daratumumab, which is a new human monoclonal antibody used to treat multiple myeloma(MM) that targets CD38, has direct antitumor and immunomodulatory activity. Recent research has found that daratumumab-based regimens are widely used in the treatment of MM. The results of several large clinical trials have confirmed the clinical benefits of daratumumab in combination with other drugs. It can be used not only for induction and consolidation therapy in newly diagnosed MM but also as a treatment option for relapsed/refractory MM, and showing potential efficacy and tolerability in long-term maintenance therapy. The data of real-world research further support the improved survival of daratumumab-based regimens in MM. This article reviews the application of daratumumab in MM based on evidence-based research.
- daratumumab /
- multiple myeloma /
- newly diagnosed /
- relapsed or refractory /
- maintenance therapy

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表 1 含达雷妥尤单抗方案治疗NDMM患者的关键临床试验

研究人群	NDMM关键研究	给药方案	患者数/例	最长随访时间/月	缓解情况				PFS/月	OS/月
研究人群	NDMM关键研究	给药方案	患者数/例	最长随访时间/月	ORR/%	≥CR率/%	≥VGPR率/%	MRD^-(灵敏度阈值10^-5)/%	PFS/月	OS/月
不适合移植的NDMM	MAIA^{[4, 7]}	D-Rd vs Rd	368 vs 369	64.5	92.9 vs 81.6	51 vs 30	81 vs 57	32.1 vs 11.1	61.9 vs 34.4	NR vs 65.5
	ALCYONE^[5]	D-VMP vs VMP	350 vs 356	78.8	90.9 vs73.9	46 vs 25	73 vs 50	28.3 vs 7.0	37.3 vs 19.7	82.7 vs 53.6
适合移植的NDMM	GRIFFIN^{[12, 14-15]}	D-VRd vs VRd	104 vs 103	49.6	99 vs 92	83 vs 60	96 vs 77	64 vs 30	4年PFS率：87.2% vs 70.0%	4年OS率：92.7% vs 92.2%
	CASSIOPEIA^[8]	D-VTd vs VTd	442 vs 444	35.4	>99 vs 99	73 vs 61	-	44 vs 30	NR vs 46.7	NR vs NR
含达雷妥尤单抗方案用法用量：①D-Rd方案[D：16 mg/kg iv，C1-C2 qw，C3-C6 q2w，C7-PD q4w；R：25 mg po d1-21，每天1次直到PD；d：40 mg po或iv，d1、8、15、22直到PD；每28 d 1个周期]；②D-VMP方案[D：16 mg/kg iv，C1 qw，C2-9 q3w，C10-PD q4w；V：1.3 mg/m²皮下注射，C1 biw，C2-9 qw；M：9 mg/m²每周期d1-4 po；P：60 mg/m²每周期d1-4 po；C1-9：每6周1个周期，C10开始：每4周1个周期]；③D-VRd方案[D-VRd诱导治疗4周期+巩固治疗2个周期，每21 d 1个周期(D：16 mg/kg iv，C1-4 qw，C5-6 q3w；V：1.3 mg/m²po，d1、4、8、11；R：25 mg po，d1-14，C1-6；d：20 mg po，d1、2、8、9、15、16、C1-6)；C7-C32 D-R维持治疗，每28 d 1个周期(D：16 mg/kg iv q8w或q4w；R：10 mg po，d1-21，C7-9；15 mg po，d1-21，C10及以上)]；④D-VTd方案[D-VTd诱导治疗4个周期+巩固治疗2个周期，每28 d 1个周期(D：16 mg/kg iv，C1-2 qw，C3-4，5-6 q2w；V：1.3 mg/m²SC，d1、4、8、11，C1-6；T：100 mg/day po，C1-6；d：20~40 mg iv/po，C1-4，20 mg iv/po，C5-6)；后续D单药维持治疗，16 mg/kg iv q8w至PD(最多使用2年)]。iv：静脉输注；po：口服；C：周期；qw：每周1次；q2w：每2周1次；q4w：每4周1次；biw：每周2次；NR，未达到；PD：疾病进展。

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表 2 含达雷妥尤单抗方案治疗RRMM患者的关键临床试验

研究人群	RRMM关键研究	给药方案	患者数/例	随访时间/月	缓解情况				中位PFS/月	中位OS/月
研究人群	RRMM关键研究	给药方案	患者数/例	随访时间/月	ORR/%	≥CR/%	≥VGPR/%	MRD^-(灵敏度阈值10^-5)/%	中位PFS/月	中位OS/月
RRMM	POLLUX^[20]	D-Rd vs Rd	286 vs 283	79.7	93 vs 76	58 vs 24	81 vs 49	33 vs 7	45.0 vs 17.5	67.6 vs 51.8
FRMM	POLLUX^[20]	D-Rd vs Rd	149 vs 146	79.7	93 vs 80	59 vs 29	80 vs 56	32 vs 10	53.5 vs 19.6	77.8 vs 57.7
RRMM	CASTOR^[21]	D-Vd vs Vd	251 vs 247	72.6	85 vs 63	30 vs 10	63 vs 29	15 vs 2	16.7 vs 7.1	49.6 vs 38.5
FRMM	CASTOR^[21]	D-Vd vs Vd	122 vs 113	72.6	92 vs 74	43 vs 15	77 vs 42	21 vs 3	27.0 vs 7.9	NR vs 47.0
RRMM	CANDOR^[22]	D-Kd vs Kd	312 vs 154	27.0	84 vs 73	33 vs 13	69 vs 47	18 vs 4	28.6 vs 15.2	-
RRMM	APOLLO^[23]	D-Pd vs Pd	151 vs 153	39.6	69 vs 47	27 vs 6	51 vs 21	-	12.1 vs 7.0	34.4 vs 23.7
含达雷妥尤单抗方案用法用量：①D-Rd[D：16 mg/kg iv C1-2 qw，C3-6 q2w，C7-PD q4w；R：25 mg po，d1-21，至PD；d：40 mg po，qw至PD]；②D-Vd[C1-8 DVd治疗每21 d 1个周期.D：C1-3 qw，C4-8 q3w；V：1.3 mg/m²sc C1-8 d1、4、8、11；d：20 mg po/iv，C1-8 d1、2、4、5、8、9、11、12；C9后仅D治疗，q4w，每28 d 1个周期]；③D-Kd[D：16 mg/kg iv C1-2 qw，C3-6 q2w，C7-PD q4w；K：56 mg/m² iv，d1、2、8、9、15、16；d：40 mg po/iv(≥75岁患者20 mg)，qw，每28 d 1个周期]；④D-Pd(达雷妥尤单抗+泊马度胺+地塞米松；D：16 mg/kg iv或1800 mg sc，C1-2 qw，C3-6 q2w，C7-PD q4w；P：4 mg/d po，d1-21；d：40 mg po，d1、8、15、22，每28 d 1个周期)。

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参考文献(30)

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研究人群	NDMM关键研究	给药方案	患者数/例	最长随访时间/月	缓解情况				PFS/月	OS/月
研究人群	NDMM关键研究	给药方案	患者数/例	最长随访时间/月	ORR/%	≥CR率/%	≥VGPR率/%	MRD^-(灵敏度阈值10^-5)/%	PFS/月	OS/月
不适合移植的NDMM	MAIA^{[4, 7]}	D-Rd vs Rd	368 vs 369	64.5	92.9 vs 81.6	51 vs 30	81 vs 57	32.1 vs 11.1	61.9 vs 34.4	NR vs 65.5
	ALCYONE^[5]	D-VMP vs VMP	350 vs 356	78.8	90.9 vs73.9	46 vs 25	73 vs 50	28.3 vs 7.0	37.3 vs 19.7	82.7 vs 53.6
适合移植的NDMM	GRIFFIN^{[12, 14-15]}	D-VRd vs VRd	104 vs 103	49.6	99 vs 92	83 vs 60	96 vs 77	64 vs 30	4年PFS率：87.2% vs 70.0%	4年OS率：92.7% vs 92.2%
	CASSIOPEIA^[8]	D-VTd vs VTd	442 vs 444	35.4	>99 vs 99	73 vs 61	-	44 vs 30	NR vs 46.7	NR vs NR
含达雷妥尤单抗方案用法用量：①D-Rd方案[D：16 mg/kg iv，C1-C2 qw，C3-C6 q2w，C7-PD q4w；R：25 mg po d1-21，每天1次直到PD；d：40 mg po或iv，d1、8、15、22直到PD；每28 d 1个周期]；②D-VMP方案[D：16 mg/kg iv，C1 qw，C2-9 q3w，C10-PD q4w；V：1.3 mg/m²皮下注射，C1 biw，C2-9 qw；M：9 mg/m²每周期d1-4 po；P：60 mg/m²每周期d1-4 po；C1-9：每6周1个周期，C10开始：每4周1个周期]；③D-VRd方案[D-VRd诱导治疗4周期+巩固治疗2个周期，每21 d 1个周期(D：16 mg/kg iv，C1-4 qw，C5-6 q3w；V：1.3 mg/m²po，d1、4、8、11；R：25 mg po，d1-14，C1-6；d：20 mg po，d1、2、8、9、15、16、C1-6)；C7-C32 D-R维持治疗，每28 d 1个周期(D：16 mg/kg iv q8w或q4w；R：10 mg po，d1-21，C7-9；15 mg po，d1-21，C10及以上)]；④D-VTd方案[D-VTd诱导治疗4个周期+巩固治疗2个周期，每28 d 1个周期(D：16 mg/kg iv，C1-2 qw，C3-4，5-6 q2w；V：1.3 mg/m²SC，d1、4、8、11，C1-6；T：100 mg/day po，C1-6；d：20~40 mg iv/po，C1-4，20 mg iv/po，C5-6)；后续D单药维持治疗，16 mg/kg iv q8w至PD(最多使用2年)]。iv：静脉输注；po：口服；C：周期；qw：每周1次；q2w：每2周1次；q4w：每4周1次；biw：每周2次；NR，未达到；PD：疾病进展。

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达雷妥尤单抗在多发性骨髓瘤中的应用

通讯作者: 陈文明，E-mail：13910107759@163.com

Application of daratumumab in multiple myeloma

Corresponding author: CHEN Wenming, E-mail: 13910107759@163.com

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达雷妥尤单抗在多发性骨髓瘤中的应用

通讯作者: 陈文明，E-mail：13910107759@163.com

Application of daratumumab in multiple myeloma

Corresponding author: CHEN Wenming, E-mail: 13910107759@163.com

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