Risk factors of postoperative venous thromboembolism in patients with multiple myeloma

doi:10.3969/j.issn.1004-583X.2023.04.009

Abstract

Abstract:

Objective To analyze risk factors of postoperative venous thromboembolism (VTE) in multiple myeloma (MM) patients. Methods One hundred and fifty seven MM patients initially treated in the Department of Hematology, the First Hospital of Shanxi Medical University from January 2012 to January 2022 were enrolled. Patients were assigned to the non-VTE group (n=124) and VTE group (n=33) based on the existence of VTE. Clinical data of the two groups were compared, and risk factors for VTE in MM patients after treatment were analyzed. Results The results of univariate analysis showed that the age, recent surgical history, recent fracture history, D-dimer>0.55 mg/L, use of immunomodulatory drugs, and IMPEDE score ≥8 points were related to the occurrence of VTE in MM patients after treatment (P<0.05). Binary multivariate logistic analysis showed that the age, recent surgical history, D-dimer >0.55 mg/L, and use of immunomodulatory drugs were the risk factors for the occurrence of VTE in MM patients.Conclusion The assessment of the risk of VTE in MM patients after treatment should be comprehensively combined with the patient's age, medical history, laboratory indicators and treatment plan. In view of the fact that the relevant score for MM patients in foreign countries may not be fully applicable to the Chinese population, further research is needed to develop the risk score for VTE in Chinese MM patients and verify it.

Key words: multiple myeloma, venous thromboembolism, risk factors, immunomodulating agents

CLC Number:

R733.3

Leng Wantong, Tao Jie. Risk factors of postoperative venous thromboembolism in patients with multiple myeloma[J]. Clinical Focus, 2023, 38(4): 340-345.

Add to citation manager EndNote|Ris|BibTeX

URL: https://huicui.hebmu.edu.cn/EN/10.3969/j.issn.1004-583X.2023.04.009

https://huicui.hebmu.edu.cn/EN/Y2023/V38/I4/340

Figures/Tables 9

References 29

[1]	Cowan AJ, Allen C, Barac A, et al. Global burden of multiple myeloma: A systematic analysis for the global burden of disease study[J]. JAMA Oncol, 2018, 4(9):1221-1227. doi: 10.1001/jamaoncol.2018.2128 URL
[2]	Yao Y, Xu Q. Progress in the study of cancer-associated venous thromboembolism[J]. Vascular, 2021, 29(3):408-414. doi: 10.1177/1708538120957443 URL
[3]	Calafiore V, Giamporcaro S, Conticello C, et al. A real-life survey of venous thromboembolic events occurring in myeloma patients treated in third line with second-generation novel agents[J]. J Clin Med, 2020, 9(9):2876. doi: 10.3390/jcm9092876 URL
[4]	Facon T, Dimopoulos MA, Dispenzieri A, et al. Final analysis of survival outcomes in the phase 3 FIRST trial of up-front treatment for multiple myeloma[J]. Blood, 2018, 131(3):301-310. doi: 10.1182/blood-2017-07-795047 pmid: 29150421
[5]	Wang H, Xu X, Pu C, et al. Clinical characteristics and prognosis of cancer patients with venous thromboembolism[J]. J Cancer Res Ther, 2019, 15(2):344-349. doi: 10.4103/jcrt.JCRT_121_18 pmid: 30964109
[6]	De Stefano V, Larocca A, Carpenedo M, et al. Thrombosis in multiple myeloma: Risk stratification, antithrombotic prophylaxis, and management of acute events. A consensus-based position paper from an ad hoc expert panel[J]. Haematologica, 2022, 107(11):2536-2547. doi: 10.3324/haematol.2022.280893 pmid: 35861017
[7]	Baker HA, Brown AR, Mahnken JD, et al. Application of risk factors for venous thromboembolism in patients with multiple myeloma starting chemotherapy, a real-world evaluation[J]. Cancer Med, 2019, 8(1):455-462. doi: 10.1002/cam4.2019.8.issue-1 URL
[8]	Bradbury CA, Craig Z, Cook G, et al. Thrombosis in patients with myeloma treated in the myeloma IX and myeloma XI phase 3 randomized controlled trials[J]. Blood, 2020, 136(9):1091-1104. doi: 10.1182/blood.2020005125 pmid: 32438407
[9]	Sanfilippo KM, Luo S, Wang TF, et al. Predicting venous thromboembolism in multiple myeloma: Development and validation of the IMPEDE VTE score[J]. Am J Hematol, 2019, 94(11):1176-1184. doi: 10.1002/ajh.25603 pmid: 31379000
[10]	Covut F, Ahmed R, Chawla S, et al. Validation of the IMPEDE VTE score for prediction of venous thromboembolism in multiple myeloma: A retrospective cohort study[J]. Br J Haematol, 2021, 193(6):1213-1219. doi: 10.1111/bjh.v193.6 URL
[11]	Khorana AA, Kuderer NM, Culakova E, et al. Development and validation of a predictive model for chemotherapy-associated thrombosis[J]. Blood, 2008, 111(10):4902-4907. doi: 10.1182/blood-2007-10-116327 pmid: 18216292
[12]	Farge D, Frere C, Connors JM, et al. 2022 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19[J]. Lancet Oncol, 2022, 23(7):e334-e347. doi: 10.1016/S1470-2045(22)00160-7 URL
[13]	Sanfilippo KM, Carson KR, Wang TF, et al. Evaluation of the Khorana score for prediction of venous thromboembolism in patients with multiple myeloma[J]. Res Pract Thromb Haemost, 2022, 6(1):e12634. doi: 10.1002/rth2.12634 URL
[14]	Sborov DW, Baljevic M, Reeves B, et al. Daratumumab plus lenalidomide, bortezomib and dexamethasone in newly diagnosed multiple myeloma: Analysis of vascular thrombotic events in the GRIFFIN study[J]. Br J Haematol, 2022, 199(3):355-365. doi: 10.1111/bjh.v199.3 URL
[15]	Charalampous C, Goel U, Kapoor P, et al. Thrombosis in multiple myeloma: Risk estimation by induction regimen and association with overall survival[J]. Am J Hematol, 2023, 98(3):413-420. doi: 10.1002/ajh.26806 pmid: 36588396
[16]	Schoen MW, Carson KR, Luo S, et al. Venous thromboembolism in multiple myeloma is associated with increased mortality[J]. Res Pract Thromb Haemost, 2020, 4(7):1203-1210. doi: 10.1002/rth2.12411 pmid: 33134785
[17]	Callander NS, Baljevic M, Adekola K, et al. NCCN Guidelines Insights: Multiple myeloma, version 3.2022[J]. J Natl Compr Canc Netw, 2022, 20(1):8-19. doi: 10.6004/jnccn.2022.0002 URL
[18]	Sanfilippo KM, Carson KR, Wang TF, et al. Evaluation of the Khorana score for prediction of venous thromboembolism in patients with multiple myeloma[J]. Res Pract Thromb Haemost, 2022, 6(1):e12634. doi: 10.1002/rth2.12634 URL
[19]	Brown JD, Adams VR. Incidence and risk factors of thromboembolism with multiple myeloma in the presence of death as a competing risk: An empirical comparison of statistical methodologies[J]. Healthcare (Basel), 2016, 4(1):16.
[20]	Li W, Garcia D, Cornell RF, et al. Cardiovascular and thrombotic complications of novel multiple myeloma therapies: a review[J]. JAMA Oncol, 2017, 3(7):980-988. doi: 10.1001/jamaoncol.2016.3350 pmid: 27632640
[21]	Hou J, Jin J, Xu Y, et al. Randomized, double-blind, placebo-controlled phase III study of ixazomib plus lenalidomide-dexamethasone in patients with relapsed/refractory multiple myeloma: China continuation study[J]. J Hematol Oncol, 2017, 10(1):137. doi: 10.1186/s13045-017-0501-4 URL
[22]	Kumar SK, Jacobus SJ, Cohen AD, et al. Carfifilzomib or bortezomib in combination with lenalidomide and dexamethasone for patients with newly diagnosed multiple myeloma without Intention for Immediate autologous stem-cell transplantation (endurance): A multicentre, open-Label, phase 3, randomised, controlled trial[J]. Lancet Oncol, 2020, 21(10):1317-1330. doi: 10.1016/S1470-2045(20)30452-6 URL
[23]	Piedra K, Peterson T, Tan C, et al. Comparison of venous thromboembolism incidence in newly diagnosed multiple myeloma patients receiving bortezomib, lenalidomide, dexamethasone (RVD) or carfifilzomib, lenalidomide, dexamethasone (KRD) with aspirin or rivaroxaban thromboprophylaxis[J]. Br J Haematol, 2022, 196(1):105-109. doi: 10.1111/bjh.v196.1 URL
[24]	Isoda A, Sato N, Miyazawa Y, et al. Silent venous thromboembolism in multiple myeloma patients treated with lenalidomide[J]. Int J Hematol, 2015, 102(3):271-277. doi: 10.1007/s12185-015-1838-5 pmid: 26177588
[25]	Fotiou D, Sergentanis TN, Papageorgiou L, et al. Longer procoagulant phospholipid-dependent clotting time, lower endogenous thrombin potential and higher tissue factor pathway inhibitor concentrations are associated with increased VTE occurrence in patients with newly diagnosed multiple myeloma: Results of the prospective ROADMAP-MM-CAT study[J]. Blood Cancer J, 2018, 8(11):102. doi: 10.1038/s41408-018-0135-y pmid: 30405097
[26]	Bravo-Perez C, Fernández-Caballero M, Soler-Espejo E, et al. Heparin versus aspirin thromboprophylaxis adds independent value to IMPEDE-VTE score for venous thrombosis prediction in multiple myeloma[J]. J Thromb Thrombolysis, 2021, 52(3):848-853. doi: 10.1007/s11239-021-02407-5
[27]	Kahale LA, Matar CF, Tsolakian I, et al. Antithrombotic therapy for ambulatory patients with multiple myeloma receiving immunomodulatory agents[J]. Cochrane Database Syst Rev, 2021, 9:CD014739.
[28]	Cornell RF, Goldhaber SZ, Engelhardt BG, et al. Primary prevention of venous thromboembolism with apixaban for multiple myeloma patients receiving immunomodulatory agents[J]. Br J Haematol, 2020, 190(4):555-561. doi: 10.1111/bjh.v190.4 URL
[29]	Storrar NPF, Mathur A, Johnson PRE, et al. Safety and efficacy of apixaban for routine thromboprophylaxis in myeloma patients treated with thalidomide- and lenalidomide-containing regimens[J]. Br J Haematol, 2019, 185(1):142-144. doi: 10.1111/bjh.2019.185.issue-1 URL

危险因素	评分(分)
恶性肿瘤性质
极高危(原发胃、胃食管交界处、胰腺肿瘤)	2
高危(原发肺、妇科、膀胱、睾丸肿瘤、淋巴瘤)	1
其他部位	0
化疗前白细胞计数>11×10⁹/L	1
化疗前血红蛋白<100 g/L或使用EPO	1
化疗前血小板计数>350×10⁹/L	1
BMI≥25 kg/m²	1

危险因素	评分(分)
恶性肿瘤性质
极高危(原发胃、胃食管交界处、胰腺肿瘤)	2
高危(原发肺、妇科、膀胱、睾丸肿瘤、淋巴瘤)	1
其他部位	0
化疗前白细胞计数>11×10⁹/L	1
化疗前血红蛋白<100 g/L或使用EPO	1
化疗前血小板计数>350×10⁹/L	1
BMI≥25 kg/m²	1

危险因素	评分
使用IMiDs	4
BMI≥35 kg/m²	1
近期骨折(骨盆,髋部或股骨)	4
使用EPO	1
使用多柔比星	3
使用地塞米松
高剂量(>160 mg/月)	4
低剂量(≤160 mg/月)	2
亚洲人/太平洋岛民	-3
既往VTE病史	5
留置中心静脉置管	2
使用治疗剂量的低分子肝素或华法林	-4
使用预防剂量的低分子肝素或阿司匹林	-3

危险因素	评分
使用IMiDs	4
BMI≥35 kg/m²	1
近期骨折(骨盆,髋部或股骨)	4
使用EPO	1
使用多柔比星	3
使用地塞米松
高剂量(>160 mg/月)	4
低剂量(≤160 mg/月)	2
亚洲人/太平洋岛民	-3
既往VTE病史	5
留置中心静脉置管	2
使用治疗剂量的低分子肝素或华法林	-4
使用预防剂量的低分子肝素或阿司匹林	-3

组别	例数	年龄 (岁)		性别[例(%)]				吸烟史 [例(%)]		饮酒史 [例(%)]		VTE病史 [例(%)]		慢性基础疾病史[例(%)]		BMI≥25 kg/m² [例(%)]		近期手术史 [例(%)]		近期骨折史 [例(%)]
组别	例数	年龄 (岁)		男		女		吸烟史 [例(%)]		饮酒史 [例(%)]		VTE病史 [例(%)]		慢性基础疾病史[例(%)]		BMI≥25 kg/m² [例(%)]		近期手术史 [例(%)]		近期骨折史 [例(%)]
非VTE组	124		63.59±9.80		76(61.3)		48(38.7)		34(27.4)		20(16.1)		7(5.6)		50(40.3)		32(25.8)		3(2.4)		4(3.2)
VTE组	33		67.55±10.60		17(51.5)		16(48.5)		7(21.2)		5(15.1)		4(12.1)		18(54.5)		7(21.2)		5(15.1)		8(24.2)
统计值			t=2.019		χ²=1.031				χ²=0.520		χ²=0.019		χ²=0.831		χ²=2.147		χ²=0.295		χ²=6.303		χ²=13.467
P值			0.045		0.310				0.471		0.892		0.362		0.143		0.587		0.012		0.000