High Incidence of Arterial Thrombosis in Young Patients Treated for Multiple Myeloma:Results of a Prospective Cohort Study.

Abstract 149

It is well known that patients with multiple myeloma (MM) are at high risk for venous thromboembolism (VTE). Thrombotic complications are most frequently seen in patients treated with thalidomide based regimens. Several other risk factors for VTE have been identified including abnormalities in coagulation factors, such as high factor VIII levels, APC resistance and hypofibrinolysis. Recently a few cases of MM patients and arterial thromboembolism (ATE) have been reported. Therefore we prospectively studied the risk of ATE in 195 consecutive patients aged <66 years with previously untreated MM. All patients were treated according to the HOVON 50 study protocol, a prospective randomized phase III study on the effects of 3 courses of doxorubicin and dexamethasone with thalidomide (TAD) or vincristine (VAD) followed by high dose melphalan and thalidomide or interferon-alpha2 maintenance or the HOVON 65 study protocol, a prospective randomised phase III study on the effects of 3 courses doxorubicin and dexamethasone with vincristine (VAD) or bortezomib (PAD), followed by high dose melphalan and bortezomib or thalidomide maintenance. All patients treated with TAD courses received prophylaxis for VTE with low molecular-weight heparin. During a follow-up of 522.4 patient-years 11 patients (5.6%) developed ATE. Most events occurred within one year after start of treatment (64%). Median age at onset of ATE was 59 years (range 43–65). For myocardial infarction we demonstrated an annual incidence of 0.77% in men and 0.19% in women compared to an equal age group, 55–59 years, described by Parikh et al in the Framingham Heart Study population who reported annual incidences of 0.22% in men and 0.04% in women, respectively. For cerebral ischemic events we demonstrated an annual incidence of 0.77% in men and 0.19% in women compared to 0.29% in men and 0.22% in women in the general Dutch population, aged 55–59, as described by Gijsen and Poos. Of thrombophilic factors a statistically significant higher factor VIII:C (FVIII:C) was observed in symptomatic patients, 2.93 IU/ml (1.16–6.45) versus 2.15 (0.74–6.48) (p=0.03). FVIII:C correlated significantly with age (p=0.02) and ISS stage (p=0.001). Adjustment for age and ISS stage, revealed a RR for ATE of 11.67 (95% CI: 2.23–61.18) for hypertension, a RR of 15.17 (1.78–129.54) for smoking and a RR of 1.85 (0.99–3.47) for each IU/ml increase in FVIII level, respectively. In conclusion, MM patients are at high risk for arterial thrombotic events during and following induction chemotherapy. High factor VIII levels, which may reflect disease activity, contribute to the risk of ATE especially in patients with known risk factors for cardiovascular disease.