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© 2020 by The American Society of HematologyNewly 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 5 1936) and Myeloma XI (n 5 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 5 121 of 538] vs 16.1% [n 5 89 of 554]; adjusted hazard ratio [aHR],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 5 68 of 425] vs 4.1% [n 5 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 5 124 of 1014] vs 13.2% [n 5 133 of 1008]; aHR 0.92; 95% CI 0.72-1.18) or arterial thrombosis (1.2% [n 5 12 of 1014] vs 1.5% [n 5 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 5 95 of 916] vs 10.7% [n 5 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 5 28 of 916] vs 1.6% [n 5 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.
Author(s): Bradbury CA, Craig Z, Cook G, Pawlyn C, Cairns DA, Hockaday A, Paterson A, Jenner MW, Jones JR, Drayson MT, Owen RG, Kaiser MF, Gregory WM, Davies FE, Anthony Child J, Morgan GJ, Jackson GH
Publication type: Article
Publication status: Published
Journal: Blood
Year: 2020
Volume: 136
Issue: 9
Pages: 1091-1104
Print publication date: 27/08/2020
Online publication date: 21/05/2020
Acceptance date: 23/04/2020
ISSN (print): 0006-4971
ISSN (electronic): 1528-0020
Publisher: American Society of Hematology
URL: https://doi.org/10.1182/blood.2020005125
DOI: 10.1182/blood.2020005125
PubMed id: 32438407
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