In the transplant-eligible cohort of the Myeloma IX study, VTE occurred in 22.5% of those treated with CVAD compared with 16.1% of patients receiving CTD (adjusted hazard ratio [aHR], 1.46; 95% CI, 1.11-1.93). In addition, in the transplant-ineligible cohort of this study, the frequencies of VTE were 16% and 4.1% for those receiving CTD vs MP (aHR, 4.25; 95% CI, 2.50-7.20).
“The high rate of thrombosis for CVAD therapy for NDMM patients may in part be related to the high-dose dexamethasone and anthracycline chemotherapy (both drugs are known to contribute to VTE risk) but perhaps more importantly, the high rate may be related to the requirement for a long-term (3-6 months) central line for administration unlike the alternative oral only regimens,” the study authors commented.
In the Myeloma XI study, risks of VTE for those receiving either thalidomide-based therapy or lenalidomide-based therapy did not differ significantly in either the transplant-eligible or transplant-ineligible cohorts. Specifically, in the transplant-eligible cohort, 12.2% and 13.2% of those treated with CRD or CTD experienced VTE (aHR, 0.92; 95% CI, 0.72-1.1) whereas in the transplant-ineligible cohort, the risks of VTE were 10.4% and 10.7% in those treated with CRD and CTDa, respectively (aHR, 0.97; 95% CI, 0.73-1.29).
However, despite use of guideline-based VTE prophylaxis in the majority of patients enrolled in the Myeloma XI trial, VTE risk remained high.
Furthermore, while thalidomide maintenance therapy did not increase VTE risk in the Myeloma IX study (1.5% [thalidomide] vs 1.7% [observation]), it was increased in those receiving lenalidomide maintenance (4.1%) compared with observation alone in the Myeloma XI study (0.6%; P <.0001).
Regarding this finding, the study authors suggested that the longer median duration of maintenance therapy in the Myeloma XI compared with the Myeloma IX trial may have contributed to this finding.
In summarizing these results, the study authors concluded that “overall, these ﬁndings suggest that patients with NDMM remain at an unacceptably high risk of VTE in spite of implementation of IMWG-guided thromboprophylaxis. Therefore, new approaches are needed, particularly in the initial 6 months of treatment.”
- Bradbury CA, Craig Z, Cook G, et al. Thrombosis in patients with myeloma treated in the Myeloma IX and Myeloma XI phase 3 randomized controlled trials. Blood. 2020;136:1091-1104. doi:10.1182/blood.2020005125
- Palumbo A, Rajkumar S, Dimopoulos M, et al. International Myeloma Working Group. Prevention of thalidomide- and lenalidomide associated thrombosis in myeloma.Leukemia. 2008;22:414-423. doi:10.1038/sj.leu.2405062