Venous Thromboembolism Is Associated with Increased Mortality in Patients with Multiple Myeloma
Authors: Sanfilippo Kristen M. , Luo Suhong , Gage Brian F , O'Brian Katiuscia , Carson Kenneth R. 
Published: October 2019

Abstract
Introduction: Previous studies have demonstrated conflicting results regarding the effect of venous thromboembolism (VTE) on survival in patients with multiple myeloma (MM). Recently, a population-based study demonstrated inferior overall survival in patients with MM and VTE (Kristinsson 2012). Given the nature of the data, the prior study was unable to verify venous thrombotic event or adjust for known confounding prognostic risk factors. In an attempt to verify the impact of VTE on survival in MM, we studied outcomes in a nationwide population of United States Veterans with MM.
Methods: Patients with newly diagnosed MM treated within the Veterans Health Administration (VHA) system between September 1, 1999 and September 30, 2009 were identified within the VHA Central Cancer Registry. To avoid including patients with precursor states (i.e. monoclonal gammopathy of undetermined significance or smoldering myeloma), patients who did not receive treatment within 6 months of diagnosis were excluded. The cohort was followed using administrative data through April 22, 2013. Data on age, sex, race, body mass index (BMI), co-morbidities, treatment including transplant status, hemoglobin (HGB), albumin, and renal function were obtained. VTE was identified using an algorithm consisting of a combination of VTE international classification of diseases (ICD)-9 codes and VTE treatment data. Cox proportional hazards regression modeling was used to assess the association between VTE and overall survival while controlling for known prognostic factors.
Results: The final analytic cohort consisted of 2785 patients of which 190 developed VTE after MM diagnosis (6.8%). After controlling for age, race, BMI, medical comorbidities, baseline lab characteristics, year of diagnosis, and upfront treatment with a novel agent (thalidomide, bortezomib, or lenalidomide), patients with MM and VTE had a 46% increased risk of death at 2 years compared to those without (table 1). This risk persisted at 5-year analysis; however, was no longer statistically significant (HR 1.16; 95% CI, 0.95-1.40).
Conclusion: After controlling for known MM prognostic factors, VTE was significantly associated with increased mortality in the 2-years following MM diagnosis. Whether the observed increase in mortality is a direct result of VTE could not be determined in this study. Further study of MM patients with a high-risk for VTE, including studies of thromboprophylaxis, could clarify the significance of this association. Table 1:Increased Risk of Death from VTE in 2,785 US Veterans with MMHR for death within 2 years of MM diagnosis (95% CI)HR for death within 5 years of MM diagnosis (95% CI)VTE1.46 (1.13-1.89)1.15 (0.95-1.40)BMI < 18.5 25 <= BMI < 30 BMI >= 301.45 (1.09-1.93) 0.87 (0.76-0.99) 0.76 (0.65-0.89)1.50 (1.18-1.92) 0.87 (0.79-0.97) 0.78 (0.69-0.88)Age (year)1.01 (1.00-1.02)1.02 (1.01-1.02)Race (AA vs. non)0.87 (0.76-0.99)0.88 (0.79-0.97)HGB mg/dL1.30 (1.15-1.47)1.26 (1.14-1.39)HGB Unknown mg/dL (n=152)0.98 (0.73-1.30)0.88 (0.71-1.10)CrCl < 30 ml/min1.47 (1.28-1.68)1.42 (1.27-1.59)CrCl Unknown ml/min (n=184)1.15 (0.89-1.49)1.11 (0.90-1.10)Albumin <=3 g/dL1.42 (1.25-1.61)1.26 (1.14-1.40)Albumin Unknown g/dL (n=366)0.76 (0.62-0.94)0.85 (0.73-1.00)Year of Diagnosis0.99 (0.96-1.01)0.97 (0.95-0.99)Charlson Comorbidity Index1.08 (1.06-1.11)1.07 (1.05-1.10)Transplant0.22 (0.15-0.31)0.46 (0.38-0.55)Upfront Treatment with Novel Therapy0.47 (0.42-0.53)0.63 (0.57-0.70)

Disclosures
Carson: Spectrum: Consultancy; Celgene: Consultancy, Speakers Bureau.