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

Autor:	Bradbury CA; School of Translational Health Sciences, University of Bristol, Bristol, United Kingdom., Craig Z; Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, United Kingdom., Cook G; Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, United Kingdom.; Leeds Cancer Centre, Leeds, United Kingdom., Pawlyn C; The Institute of Cancer Research, London, United Kingdom.; The Royal Marsden Hospital National Health Service (NHS) Foundation Trust, London, United Kingdom., Cairns DA; Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, United Kingdom., Hockaday A; Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, United Kingdom., Paterson A; Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, United Kingdom., Jenner MW; University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom., Jones JR; Kings College Hospital NHS Foundation Trust, London, United Kingdom., Drayson MT; Clinical Immunology, School of Immunity and Infection, University of Birmingham, Birmingham, United Kingdom., Owen RG; Haematological Malignancy Diagnostic Service, St James's University Hospital, Leeds, United Kingdom., Kaiser MF; The Institute of Cancer Research, London, United Kingdom.; The Royal Marsden Hospital National Health Service (NHS) Foundation Trust, London, United Kingdom., Gregory WM; Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, United Kingdom., Davies FE; Perlmutter Cancer Center, New York University Langone Health, New York, NY; and., Child JA; Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, United Kingdom., Morgan GJ; Perlmutter Cancer Center, New York University Langone Health, New York, NY; and., Jackson GH; Freeman Hospital, University of Newcastle, Newcastle Upon Tyne, United Kingdom.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2020 Aug 27; Vol. 136 (9), pp. 1091-1104.
DOI:	10.1182/blood.2020005125
Abstrakt:	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 [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 = 68 of 425] vs 4.1% [n = 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. (© 2020 by The American Society of Hematology.)
Databáze:	MEDLINE
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