External Validation of the Impede VTE Risk Score in Newly Diagnosed Multiple Myeloma (MM) Patients
Authors: Covut Fahrettin , Ahmed Ramsha , Samaras Christy J. , Anwer Faiz , Mejia Garcia Alex V. , Angelini Dana E , Faiman Beth M. , Reed Janice , Karam Mary Ann , Schlueter Kristen , Mathur Saveta , Hamilton Kimberly , Rosko Nathaniel , Valent Jason , Khouri Jack 
Published: November 2019

Background: Venous thromboembolism (VTE) is a prevalent cause of morbidity in MM patients. The IMPEDE VTE score was recently proposed by Sanfilippo KM et al. in 2018 ASH annual meeting to predict VTE in MM. Herein, we report on the external validation of this score.
Methods: We reviewed consecutive newly diagnosed MM patients who were treated at the Cleveland Clinic between 2010 and 2012. All treatment variables were collected as time-varying variables. Poor cytogenetic features were defined as monosomy 13 or 17, t(4;14), or t(4;16). We calculated the total IMPEDE VTE score for each patient as previously defined; immunomodulatory drug (IMiD) use (+3), BMI >25 kg/m2 (+1), pathologic pelvis/femur fracture (+2), erythropoiesis-stimulating agent use (+1), low/high dexamethasone use (+2/+4), doxorubicin use (+2), Asian race (-3), history of VTE (+3), central venous catheter use (+2), prophylactic aspirin or enoxaparin (-2), therapeutic anticoagulation (-5). Patients with IMPEDE VTE score of <3, 3 to 6, and >6 were defined as low-, intermediate-, and high-risk groups, respectively. Cumulative incidence of symptomatic VTE after initiation of systemic treatment was calculated with death as competing risk and compared with the Gray's test. Overall survival (OS) was estimated by the Kaplan-Meier method and compared with the log-rank test. Multivariable Cox analysis was used to identify independent predictors of OS.
Results: We identified 210 MM patients, 102 (49%) were female, 31 (15%) were black, and median age at diagnosis was 63 years (range: 30 - 91). Fifteen (7%) patients had VTE prior to MM diagnosis and 30 (14%) patients had pathologic pelvic or femur fracture at or after MM diagnosis. Poor cytogenetic features were seen in 65 (31%) patients. ECOG performance status at diagnosis was ≥2 for 33 (16%) patients. Sixty-seven (32%), 65 (31%), and 57 (27%) patients had ISS stage I, II, and III disease, respectively. MM subtypes were IgG, IgA, and light-chain disease for 109 (52%), 46 (22%), and 52 (25%) patients, respectively. IMiDs and low-dose dexamethasone were given to 145 (69%) and 205 (98%) patients, respectively. Seventy-seven (37%) patients underwent autologous hematopoietic cell transplant. Patient and treatment characteristics were compared between patients with and without VTE after MM diagnosis in Table 1.
Twenty-two (10%) patients had symptomatic VTE within 6 months after initiation of systemic treatment for MM. When IMPEDE VTE score was calculated based on the risk factors during this time period, 37 (18%), 157 (75%), and 16 (8%) patients were in low-, intermediate- and high-risk groups, respectively. Six-months cumulative incidence of VTE in low-, intermediate- and high-risk groups were 2.7% (95% CI: 0 - 7.9), 10.8% (95% CI: 6.0 - 15.7), and 25% (95% CI: 3.8 - 46.2), respectively (p=0.011) (Figure 1A). Whereas, 39 (19%) patients were diagnosed with symptomatic VTE during median follow-up of 86 months. When the highest IMPEDE VTE score for each patient was calculated based on the risk factors at any time after initiation of treatment, 16 (8%), 151 (72%), and 43 (20%) patients were in low-, intermediate-, and high-risk groups, respectively. Seven-year cumulative incidence of VTE in low-, intermediate- and high-risk groups were 9.0% (95% CI: 0 - 25.7), 16.3% (95% CI: 10.3 - 22.3), and 29.3 (95% CI: 15.2 - 43.3), respectively (p=0.014) (Figure 1B).
Seven-year OS of patients with and without VTE within 6 months after initiation of treatment was 50% (95% CI: 32% - 79%) and 46% (95% CI: 39% - 55%), respectively (p=0.4). On multivariable analysis, VTE vs no VTE within 6 months after initiation of treatment did not predict OS (HR 1.10, 95% CI: 0.46 - 2.66, p=0.8), whereas each 1-year increase in age (HR 0.99, 95% CI: 0.96 - 1.02, p=0.61), each 1 increase in ECOG performance status (HR 1.77, 95% CI: 1.24 - 2.53, p=0.002) and ISS stage (HR 1.50, 95% CI: 1.06 - 1.14, p=0.024), poor vs non-poor cytogenetics features (HR 4.38, 95% CI: 2.25 - 8.57, p<0.0001), high vs normal LDH (HR 1.94, 95% CI: 1.05 - 3.60, p=0.035), IMiD use vs non-use at first induction (HR 0.52, 95% CI: 0.29 - 0.43, p=0.026), and transplant vs no transplant (HR 0.40, 95% CI: 0.20 - 0.79, p=0.008) were statistically significant predictors of OS (Table 2).
Conclusion: In this cohort of MM patients, we showed that IMPEDE VTE score was able to stratify patients into distinct risk groups and can be a helpful tool to provide personalized strategies for thromboprophylaxis.

Disclosures
Anwer: In-Cyte: Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Valent:Takeda pharmaceuticals: Speakers Bureau; Amgen corporation: Speakers Bureau; Celgene corporation: Speakers Bureau.