Abstract
BackgroundThere is a well-established link between myeloma and venous thromboembolism (VTE). The optimal VTE prophylaxis strategy is unknown.
Aims
To assess apixaban as thromboprophylaxis in newly diagnosed multiple myeloma (NDMM) patients. This feasibility study aims to determine which biomarkers of thrombosis warrant further investigation in a larger clinical trial. Patient perspectives were sought on trial design and knowledge of thrombotic risk.
Methods
The TiMM trial randomised patients to either aspirin 75mg once daily (OD) if standard VTE risk, or enoxaparin 40mg OD if high risk vs. apixaban 2.5mg twice daily. The primary end point was bleeding or an objectively diagnosed VTE. Biomarkers were compared with control samples at baseline and regular intervals following initiation of chemotherapy. Two one-hour focus groups were performed at King’s College and Guy’s Hospital, London. They were recorded, transcribed and themes explored using NVivo 11.
Results
Ten patients were recruited to the TiMM feasibility clinical trial; two high-risk receiving apixaban, eight standard risk; four randomised to aspirin, four to apixaban. There were no major bleeding events. Two cannula-associated thrombosis occurred.
Fibrinogen was elevated in NDMM patients at all time points compared with controls. There are increased FVIII, VWF:Ag and Act which increases over the first four visits, following which, they normalise by week 18. Neutrophil extracellular traps (NETs) is elevated at all visits and continues to increase for the duration of the trial. NETs is higher at baseline in those who experienced cannula-associated thrombosis. These biomarkers require further investigation in a larger clinical trial.
Patients were not aware of the thrombotic risk associated with cancer. There is a lack of written and verbal information available. Patients were happy to be co-recruited to more than one trial simultaneously.
Conclusions
No safety concerns were raised about apixaban in this setting. FVIII and VWF:Ag and Act may indicate that the risk of VTE is elevated, potentially increases during the first 9 weeks of chemotherapy, and reduces by week 18. This could be useful in identifying when to discontinue thromboprophylaxis and which patients may be at highest risk of VTE. NETs warrant further investigation in a larger clinical trial. Patients with cancer require more information about the thrombotic risk.
Keywords: multiple myeloma, DOACs, apixaban, venous thromboembolism, thromboprophylaxis, aspirin, enoxaparin, clinical trial
| Date of Award | 1 Mar 2021 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Roopen Arya (Supervisor) & Jignesh Patel (Supervisor) |