Two phase 3 clinical trials characterized the risk for venous thrombosis (VTE) in patients with newly diagnosed multiple myeloma (NDMM), while receiving different treatments. The trials were recently analyzed together in a study published in the journal Blood.
The study authors explained that patients who have NDMM show an increased risk for VTE, and this risk is further enhanced with treatment using immunomodulatory agents. In their analysis, they examined VTE risks for patients in the Myeloma IX trial (ISRCTN684564111) and Myeloma XI trial (ISRCTN49407852), both of which were randomized, controlled trials based in the United Kingdom.
In the Myeloma IX study (1936 participants), transplant-eligible patients with NDMM received pretransplant treatment with either cyclophosphamide, thalidomide, and dexamethasone (CTD) or cyclophosphamide, vincristine, doxorubicin, and dexamethasone (CVAD). Transplant-ineligible patients with NDMM were given induction therapy with either melphalan plus prednisolone (MP) or attenuated CTD. The median study follow-up was 71 months.
In Myeloma XI (4358 participants), patients with NDMM who were eligible for transplant received either cyclophosphamide, lenalidomide, and dexamethasone (CRD) or CTD. Transplant-ineligible patients received either attenuated CRD or attenuated CTD. The median study follow-up was 60 months.
For transplant-eligible patients in the Myeloma IX trial, patients receiving CVAD had a greater risk for VTE (22.5%) than patients treated with CTD (16.1%; adjusted hazard ratio [aHR], 1.46; 95% CI, 1.11-1.93). Transplant-ineligible patients in the Myeloma IX trial showed VTE risks of 16.0% with attenuated CTD and 4.1% with MP (aHR, 4.25; 95% CI, 2.50-7.20).
Differences in VTE risk were not apparent between groups in the Myeloma XI trial. Transplant-eligible patients in this trial had VTE risks of 12.2% with CRD and 13.2% with CTD (aHR, 0.92; 95% CI, 0.72-1.18). Transplant-ineligible patients showed VTE risks of 10.4% with attenuated CRD and 10.7% with attenuated CTD (aHR, 0.97; 95% CI, 0.73-1.29) in this trial.
Arterial thrombosis risk was also considered in Myeloma XI. In transplant-eligible patients, arterial thrombosis risks were 1.2% for patients receiving CRD and 1.5% with CTD (aHR, 0.80; 95% CI, 0.37-1.70). Transplant-ineligible patients showed slight differences by treatment group in risk of arterial thrombosis, with rates of 3.1% for attenuated CRD and 1.6% for attenuated CTD (aHR, 1.91; 95% CI, 1.02-3.57).
The investigators reported that progression-free and overall survival rates were similar regardless of thrombosis risk. The exception was lower overall survival for patients who had arterial thrombosis events in the Myeloma XI study (aHR, 1.53; 95% CI, 1.12-2.08).
The authors noted that thromboprophylaxis was given at a much higher rate with the Myeloma XI trial (80.5%) than on the Myeloma IX trial (22.3%), but that overall the risk of VTE was still unacceptably elevated.
“Therefore, new approaches are needed, particularly in the initial 6 months of treatment,” the researchers concluded.
Disclosures: Several study authors have declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Bradbury C, Craig Z, Cook G, et al. Thrombosis in patients with myeloma treated in the Myeloma IX and Myeloma XI phase III randomized controlled trials [published online May 21, 2020]. Blood. doi: 10.1182/blood.2020005125