寡克隆条带和(或)Ig同型转换对多发性骨髓瘤的疗效和预后评价的意义

曹莉; 王莹; 曹江; 齐昆明; 程海; 朱锋; 孙海英; 闫志凌; 桑威; 李德鹏; 李振宇; 徐开林

doi:10.13201/j.issn.1004-2806.2022.09.007

寡克隆条带和(或)Ig同型转换对多发性骨髓瘤的疗效和预后评价的意义

- 1.
  徐州医科大学血液病研究所(江苏徐州，221000)
- 2.
  徐州医科大学附属医院血液科

详细信息

通讯作者: 徐开林，E-mail：lihmd@163.com

中图分类号: R733.3

收稿日期: 2022-05-13

刊出日期: 2022-09-01

The effect and prognostic evaluation of oligoclonal protein bands and/or immune-globulinisotype switch to multiple myeloma

- 1.
  Institute of Hematology, Xuzhou Medical University, Xuzhou, 221000, China
- 2.
  Department of Hematology, Affiliated Hospital of Xuzhou Medical University

More Information

Corresponding author: XU Kailin, E-mail: lihmd@163.com

Received Date: 13 May 2022

Publish Date: 01 September 2022

摘要

摘要: 目的研究多发性骨髓瘤(MM)治疗后出现寡克隆条带和(或)Ig同型转换对疗效和预后评价的意义。方法回顾性分析2018年8月—2021年7月接受化疗、自体造血干细胞移植(ASCT)、嵌合抗原受体T细胞(CAR-T)治疗的连续入组的72例MM患者的临床资料，应用免疫固定电泳检测M蛋白。结果 8例(11.1%)患者发生异常蛋白条带(APB)，APB持续中位时间为2.5(1.1，6.3)个月，诊断MM至出现APB的中位时间为12.5(9.5，34.8)个月，发生APB前的末次治疗至出现APB的中位时间为2.2(0.7，5.7)个月。APB的发生与性别、年龄、ECOG评分、肌酐、血钙、乳酸脱氢酶、血红蛋白、血小板计数、骨髓浆细胞比例、染色体核型等基线特点无关，与β2-微球蛋白和总蛋白水平相关(P< 0.05)。APB组≥非常好的部分缓解率明显高于非APB组(100.0% vs 42.2%)，差异有统计学意义(P=0.002)。APB组患者的中位生存期为25(95%CI18~27)个月，非APB组患者的中位生存期为23(95%CI18~27)个月，2组比较差异无统计学意义。接受化疗和ASCT治疗的患者中，APB组较非APB组的生存时间长，但差异无统计学意义；接受CAR-T细胞治疗的患者中，非APB组的中位生存时间为23(95%CI20~28)个月，明显低于APB组的54(95%CI39~54)个月，差异有统计学意义(P=0.028)。结论在不同方案治疗后出现APB的患者具有更好的疗效；CAR-T细胞治疗后发生APB的患者预后更好。
- 多发性骨髓瘤 /
- 异常蛋白条带 /
- 蛋白酶体抑制剂 /
- 自体造血干细胞移植 /
- 嵌合抗原受体T细胞治疗
Abstract: Objective To investigate the effect and prognostic evaluation of oligoclonal protein bands and/or immune-globulin(Ig) isotype switch among multiple myeloma(MM) patients.Methods A total of 72 MM patients who received chemotherapy, autologous hematopoietic stem cell transplantation(ASCT), and chimeric antigen receptor T-cell(CAR-T) therapy from August 2018 to July 2021 were retrospectively analyzed. Monoclonal protein was detected by immunofixation electrophoresis.Results Abnormal protein band(APB) occurred in 8(11.1%) MM patients. The median duration of APB was 2.5(1.1, 6.3) months. The median time from diagnosis and the last treatment of MM to the onset of APB was 12.5(9.5, 34.8) and 2.2(0.7, 5.7) months, respectively. The occurrence of APB was not related to baseline characteristics such as sex, age, ECOG score, creatinine, serum calcium, lactate dehydrogenase, hemoglobin, platelet count, bone marrow plasma cell ratio, chromosome karyotype, but was related to the level of β2-microglobulin and total protein(P< 0.05). The very good partial response rate in the APB group was significantly higher than that in the non-APB group(100.0% vs 42.2%,P=0.002). The median overall survival in the APB group was 25(95%CI18-27) months, and in the non-APB group was 23(95%CI18-27) months, there was no significant difference between the two groups. The median overall survival of patients with APB in the chemotherapy group and the ASCT group seemed longer than that of patients without APB, but there was no significant difference. Among patients who received CAR-T cell therapy, the median overall survival in patients without APB was 23(95%CI20-28) months, which was significantly lower than that of 54(95%CI39-54) months in patients with APB(P=0.028).Conclusion Patients who had APB have a better response to chemotherapy, ASCT, or CAR-T cell therapy. The occurrence of APB suggests a better prognosis in MM patients who received CAR-T cell therapy.
- multiple myeloma /
- abnormal protein bands /
- proteasome inhibitor /
- autologous hematopoietic stem cell transplantation /
- chimeric antigen receptor T-cell therapy

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图 1 APB组和非APB组间生存时间的log-rank检验图

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表 1 APB患者M蛋白类型

序号	年龄/岁	性别	原始类型	治疗方式	APB	确诊到出现APB的时间/月	出现APB时的疗效
1	74	男	IgA λ	化疗	IgG κ	6	VGPR
2	68	男	IgA	化疗	IgA κ	9	VGPR
3	78	女	κ	化疗	IgG κ	11	VGPR
4	61	男	κ	ASCT	IgG λ	12	CR
5	62	女	λ	ASCT	IgG λ	34	CR
6	55	男	IgD λ	CAR-T	λ	35	CR
7	47	男	IgD λ	CAR-T	IgG	36	CR
8	60	男	IgA κ	CAR-T	IgG λ	13	CR

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表 2 发生APB和未发生APB患者间临床特征比较

临床特征	发生APB	未发生APB	χ²/U	P
例数	8	64
性别/例(%)				0.455
男	6(75.0)	36(56.3)
女	2(25.0)	28(43.7)
年龄/岁	61(55，74)	60(56，66)	284.0	0.616
ECOG评分/分	1(1，2)	1(1，2)	242.5	0.789
β2-MG/(μg·L^-1)	2 302.0(2 105.0，4 579.0)	5 192.0(3 083.8，7 772.5)	142.5	0.042
总蛋白/(g·L^-1)	74.5(58.4，90.2)	92.0(73.6，105.9)	113.5	0.013
白蛋白/(g·L^-1)	41.2(38.4，41.9)	36.1(31.5，40.1)	342.0	0.066
肌酐/(μmol·L^-1)	70.0(48.0，147.0)	69.0(54.0，114.3)	282.0	0.641
血钙/(mmol·L^-1)	2.2(2.1，2.5)	2.2(2.0，2.4)	262.5	0.411
LDH/(mmol·L^-1)	260.0(156.0，392.0)	176.5(149.3，251.8)	314.5	0.186
血红蛋白/(g·L^-1)	82.0(66.0，101.0)	88.5(72.0，110.3)	211.5	0.425
血小板计数/(×10⁹·L^-1)	148.0(73.0，193.0)	157.0(107.0，205.0)	214.0	0.452
骨髓浆细胞比例/%	28.0(32.0，47.0)	33.5(16.1，57.1)	248.0	0.999
细胞遗传/例(%)			0.277	0.599
染色体正常	7(87.5)	51(79.7)
染色体异常	1(12.5)	13(20.3)
ISS分期/例(%)			9.654	0.008
Ⅰ期	4(50.0)	7(10.9)
Ⅱ期	3(37.5)	22(34.4)
Ⅲ期	1(12.5)	35(54.7)
类型/例(%)			12.353	0.015
IgA	3(37.5)	10(15.6)
IgD	2(25.0)	4(6.3)
IgG	0	39(60.9)
λ/κ	3(37.5)	9(14.1)
未分泌	0	2(3.1)
治疗方案/例(%)			0.113	0.945
化疗	3(37.5)	27(42.2)
ASCT	2(25.0)	13(20.3)
CAR-T	3(37.5)	24(37.5)

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表 3 APB发生影响因素的logistic回归模型

ISS分期	β	SE	OR	95% CI	P
Ⅰ期	1(reference)
Ⅱ期	-1.047	1.223	0.35	0.03~3.85	0.392
Ⅲ期	-3.135	1.392	0.04	0.01~0.67	0.024

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表 4 CAR-T细胞治疗后发生APB和未发生APB患者间临床特征比较

临床特征	未发生APB	发生APB	χ²/U	P
例数	24	3
性别/例(%)				0.545
男	17(70.8)	3(100.0)
女	7(29.2)	0
年龄/岁	59(56，64)	55(47，55)	18.5	0.187
β2-MG/(μg·L^-1)	3 789.0(3 017.0，6 753.0)	2 105.0(1 987.0，2 105.0)	4.5	0.008
总蛋白/(g·L^-1)	93.8(69.0，104.9)	74.5(58.4，74.5)	23.5	0.351
白蛋白/(g·L^-1)	36.7(33.0，39.5)	41.2(41.0，41.2)	59.5	0.041
肌酐/(μmol·L^-1)	66.0(54.0，87.0)	48.0(47.0，48.0)	27.5	0.532
血钙/(mmol·L^-1)	2.2(2.0，2.3)	2.2(2.1，2.2)	38.0	0.914
LDH/(mmol·L^-1)	173.0(144.0，241.0)	260.0(144.0，260.0)	48.5	0.351
血红蛋白/(g·L^-1)	70.0(75.0，106.0)	73.0(69.0，73.0)	19.0	0.215
血小板计数/(×10⁹·L^-1)	164.0(108.0，209.0)	73.0(69.0，73.0)	20.5	0.245
骨髓浆细胞比例/%	35.0(19.0，49.0)	32.0(15.0，32.0)	33.0	0.856
ISS分期/例(%)			17.6	< 0.001
Ⅰ期	0	2(66.7)
Ⅱ期	12(50.0)	1(33.3)
Ⅲ期	12(50.0)	0
类型/例(%)			6.7	0.150
IgA	4(16.7)	1(33.3)
IgD	3(12.5)	2(66.7)
IgG	12(50.0)	0
λ/κ	3(12.5)	0
未分泌	2(8.3)	0

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