Thrombosis in patients with myeloma treated in the Myeloma IX and Myeloma XI phase 3 randomized controlled trials

被引:64
作者
Bradbury, Charlotte A. [1 ]
Craig, Zoe [2 ]
Cook, Gordon [2 ,3 ]
Pawlyn, Charlotte [4 ,5 ]
Cairns, David A. [2 ]
Hockaday, Anna [2 ]
Paterson, Andrea [2 ]
Jenner, Matthew W. [6 ]
Jones, John R. [7 ]
Drayson, Mark T. [8 ]
Owen, Roger G. [9 ]
Kaiser, Martin F. [4 ,5 ]
Gregory, Walter M. [2 ]
Davies, Faith E. [10 ]
Child, J. Anthony [2 ]
Morgan, Gareth J. [10 ]
Jackson, Graham H. [11 ]
机构
[1] Univ Bristol, Sch Translat Hlth Sci, Bristol, Avon, England
[2] Univ Leeds, Leeds Inst Clin Trials Res, Clin Trials Res Unit, Leeds, W Yorkshire, England
[3] Leeds Canc Ctr, Leeds, W Yorkshire, England
[4] Inst Canc Res, London, England
[5] Royal Marsden Hosp Natl Hlth Serv NHS Fdn Trust, London, England
[6] Univ Hosp Southampton NHS Fdn Trust, Southampton, Hants, England
[7] Kings Coll Hosp NHS Fdn Trust, London, England
[8] Univ Birmingham, Sch Immun & Infect, Clin Immunol, Birmingham, W Midlands, England
[9] St James Univ Hosp, Haematol Malignancy Diagnost Serv, Leeds, W Yorkshire, England
[10] New York Univ Langone Hlth, Perlmutter Canc Ctr, New York, NY USA
[11] Univ Newcastle, Freeman Hosp, Newcastle Upon Tyne, Tyne & Wear, England
基金
英国医学研究理事会;
关键词
DIAGNOSED MULTIPLE-MYELOMA; VENOUS THROMBOEMBOLISM; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY; CELL TRANSPLANTATION; THALIDOMIDE; LENALIDOMIDE; THERAPY; DEXAMETHASONE; THROMBOPROPHYLAXIS;
D O I
10.1182/blood.2020005125
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Newly diagnosed multiple myeloma (NDMM) patients treated with immunomodulatory drugs are at high risk of venous thromboembolism (VTE), but data are lacking from large prospective cohorts. We present thrombosis outcome data from Myeloma IX (n = 1936) and Myeloma XI (n = 4358) phase 3 randomized controlled trials for NDMM that treated transplant-eligible and transplant-ineligible patients before and after publication of thrombosis prevention guidelines. In Myeloma IX, transplant-eligible patients randomly assigned to cyclophosphamide, vincristine, doxorubicin, and dexamethasone (CVAD) induction had higher risk of VTE compared with patients treated with cyclophosphamide, thalidomide, and dexamethasone (CTD) (22.5% [n = 121 of 538] vs 16.1% [n = 89 of 554]; adjusted hazard ratio [aH12],1.46; 95% confidence interval [95% CI], 1.11-1.93). For transplant-ineligible patients, those randomly assigned to attenuated CTD (CTDa) induction had a higher risk of VTE compared with those treated with melphalan and prednisolone (MP) (16.0% [n = 68 of 425] vs 4.1% En = 17 of 419]; aHR, 4.25; 95% CI, 2.50-7.20). In Myeloma XI, there was no difference in risk of VTE (12.2% [n = 124 of 1014] vs 13.2% [n = 133 of 1008]; aHR, 0.92; 95% CI, 0.72-1.18) or arterial thrombosis (1.2% [n = 12 of 1014] vs 1.5% [n = 15 of 1008]; aHR, 0.80; 95% CI, 0.37-1.70) between transplant-eligible pathways for patients treated with cyclophosphamide, lenalidomide, and dexamethasone (CRD) or CTD. For transplant-ineligible patients, there was no difference in VTEs between attenuated CRD (CRDa) and CTDa (10.4% [n = 95 of 916] vs 10.7% [n = 97 of 910]; aHR, 0.97; 95% CI, 0.73-1.29). However, arterial risk was higher with CRDa than with CTDa (3.1% [n = 28 of 916] vs 1.6% [n = 15 of 910]; aHR, 1.91; 95% CI, 1.02-3.57). Thrombotic events occurred almost entirely within 6 months of treatment initiation. Thrombosis was not associated with inferior progression-free survival (PFS) or overall survival (OS), apart from inferior OS for patients with arterial events (aHR, 1.53; 95% CI, 1.12-2.08) in Myeloma XI. The Myeloma XI trial protocol incorporated International Myeloma Working Group (IMWG) thrombosis prevention recommendations and compared with Myeloma IX, more patients received thromboprophylaxis (80.5% vs 22.3%) with lower rates of VTE for identical regimens (CTD, 13.2% vs 16.1%; CTDa, 10.7% vs 16.0%). However, thrombosis remained frequent in spite of IMWG-guided thromboprophylaxis, suggesting that new approaches are needed.
引用
收藏
页码:1091 / 1104
页数:14
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