Venous thromboembolism (VTE) is a common cause of morbidity and mortality among patients with multiple myeloma (MM). The International Myeloma Working Group (IMWG) developed guidelines recommending primary thromboprophylaxis, in those identified at high‐risk of VTE by the presence of risk factors. The National Comprehensive Cancer Network (NCCN) has adopted these guidelines; however, they lack validation. We sought to develop and validate a risk prediction score for VTE in MM and to evaluate the performance of the current IMWG/NCCN guidelines. Using 4446 patients within the Veterans Administration Central Cancer Registry, we used time‐to‐event analyses to develop a risk score for VTE in patients with newly diagnosed MM starting chemotherapy. We externally validated the score using the Surveillance, Epidemiology, End Results (SEER)‐Medicare database (N = 4256). After identifying independent predictors of VTE, we combined the variables to develop the IMPEDE VTE score (Immunomodulatory agent; Body Mass Index ≥25 kg/m2; Pelvic, hip or femur fracture; Erythropoietin stimulating agent; Dexamethasone/Doxorubicin; Asian Ethnicity/Race; VTE history; Tunneled line/central venous catheter; Existing thromboprophylaxis). The score showed satisfactory discrimination in the derivation cohort, c‐statistic = 0.66. Risk of VTE significantly increased as score increased (hazard ratio 1.20, P = <.0001). Within the external validation cohort, IMPEDE VTE had a c‐statistic of 0.64. For comparison, when evaluating the performance of the IMWG/NCCN guidelines, the c‐statistic was 0.55. In summary, the IMPEDE VTE score outperformed the current IMWG/NCCN guidelines and could be considered as the new standard risk stratification for VTE in MM.

Background: Although venous thromboembolism (VTE) is a significant complication for patients with multiple myeloma (MM) receiving immunomodulatory drugs (IMiDs), no validated clinical model predicts VTE in this population. This study aimed to derive and validate a new risk assessment model (RAM) for IMiD-associated VTE. Methods: Patients with newly diagnosed MM receiving IMiDs were selected from the SEER-Medicare database (n=2,397) to derive a RAM and then data from the Veterans Health Administration database (n=1,251) were used to externally validate the model. A multivariable cause-specific Cox regression model was used for model development. Results: The final RAM, named the “SAVED” score, included 5 clinical variables: prior surgery, Asian race, VTE history, age ≥80 years, and dexamethasone dose. The model stratified approximately 30% of patients in both the derivation and the validation cohorts as high-risk. Hazard ratios (HRs) were 1.85 (P<.01) and 1.98 (P<.01) for high- versus low-risk groups in the derivation and validation cohorts, respectively. In contrast, the method of stratification recommended in the current NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease had HRs of 1.21 (P=.17) and 1.41 (P=.07) for the corresponding risk groups in the 2 datasets. Conclusions: The SAVED score outperformed the current NCCN Guidelines in risk-stratification of patients with MM receiving IMiD therapy. This clinical model can help inform providers and patients of VTE risk before IMiD initiation and provides a simplified clinical backbone for further prognostic biomarker development in this population.

A B S T R A C T PurposeObesity increases the risk of death from many malignancies, including non-Hodgkin's lymphoma (NHL). In diffuse large B-cell lymphoma (DLBCL), the most common form of NHL, the association between body mass index (BMI) at diagnosis and survival is unclear. Patients and MethodsWe evaluated the association between BMI at diagnosis and overall survival in a retrospective cohort of 2,534 United States veterans diagnosed with DLBCL between October 1, 1998 and December 31, 2008. Cox modeling was used to control for patient-and disease-related prognostic variables. ResultsMean age at diagnosis was 68 years (range, 20 to 100 years); 64% of patients were overweight (BMI, 25 to Ͻ 30) or obese (BMI, Ն 30). Obese patients were significantly younger, had significantly fewer B symptoms, and trended toward lower-stage disease, compared with other BMI groups. Cox analysis showed reduced mortality in overweight and obese patients (overweight: hazard ratio [HR], 0.73; 95% CI, 0.65 to 0.83; obese: HR, 0.68; 95% CI, 0.58 to 0.80), compared with normal-weight patients (BMI, 18.5 to Ͻ 25). Treatment during the rituximab era reduced the risk of death without affecting the association between BMI and survival. Diseaserelated weight loss occurred in 29% of patients with weight data 1 year before diagnosis. Cox analysis based on BMI 1 year before diagnosis continued to demonstrate reduced risk of death in overweight and obese patients. ConclusionBeing overweight or obese at the time of DLBCL diagnosis is associated with improved overall survival. Understanding the mechanisms responsible for this association will require further study.

The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) have activity in one of the pathways influenced by nitrogen-containing bisphosphonates, which are associated with improved survival in multiple myeloma (MM). To understand the benefit of statins in MM, we evaluated the association between statin use and mortality in a large cohort of patients with MM. Patients and MethodsFrom the Veterans Administration Central Cancer Registry, we identified patients diagnosed with MM between 1999 and 2013. We defined statin use as the presence of any prescription for a statin within 3 months before or any time after MM diagnosis. Cox proportional hazards regression assessed the association of statin use with mortality, while controlling for known MM prognostic factors. ResultsWe identified a cohort of 4,957 patients, of whom 2,294 received statin therapy. Statin use was associated with a 21% decrease in all-cause mortality (adjusted hazard ratio, 0.79; 95% CI, 0.73 to 0.86; P , .001) as well as a 24% decrease in MM-specific mortality (adjusted hazard ratio, 0.76; 95% CI, 0.67 to 0.86; P , .001). This association remained significant across all sensitivity analyses. In addition to reductions in mortality, statin use was associated with a 31% decreased risk of developing a skeletal-related event. ConclusionIn this cohort study of US veterans with MM, statin therapy was associated with a reduced risk of both all-cause and MM-specific mortality. Our findings suggest a potential role for statin therapy in patients with MM. The putative benefit of statin therapy in MM should be corroborated in prospective studies.

Introduction Patients with non-Hodgkin lymphoma (NHL) have an increased risk of venous thromboembolism (VTE). Current risk-prediction models classify NHL as a single entity. We aimed to quantify the difference in VTE risk in follicular lymphoma (FL) versus diffuse large B cell lymphoma (DLBCL). Methods Using a prospective cohort study, we identified 2,730 patients (2,037 DLBCL; 693 FL) within the Veteran’s Administration Central Cancer Registry. A competing risk model assessed the association between VTE risk and histology in the first year after NHL diagnosis. We assessed the effect of additional risk factors for VTE in NHL. Results In univariate analysis, DLBCL was associated with increased risk of VTE compared to FL in the first year after diagnosis; this association was no longer significant in adjusted analysis (adjusted hazard ratio (aHR) 1.52; 95% CI 0.97–2.40). Major risk factors for VTE included history of VTE before NHL diagnosis (aHR 4.73, p=<0.0001) and time period during chemotherapy administration (aHR 7.60, p=<0.0001). Additional risk factors included: stage III/IV disease (p=0.02), BMI ≥ 30 (p=0.02), B-symptoms (p=0.02), and doxorubicin (p=0.04). The cumulative incidence of VTE was highest in the period following diagnosis and decreased over time for both histologies. Conclusion DLBCL is associated with increased risk of VTE compared to FL. This risk is markedly attenuated when adjusting for additional risk factors. The strongest predictors for development of VTE included: time period during chemotherapy administration (especially doxorubicin) and history of VTE. This knowledge can assist clinicians in identifying NHL patients at high risk for VTE.

Background Multiple myeloma (MM) is one of the most common hematologic malignancies in the United States and is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS). Methods A retrospective cohort of patients in the U.S. Veterans Health Administration database diagnosed with MGUS between 1, October, 1999 and 31, December, 2009 and diabetes mellitus prior to their MGUS diagnosis was identified and followed through 6, August, 2013. Patient-level clinical data were reviewed to verify diagnoses and to abstract data on size of baseline M-protein and type of MGUS, i.e., immunoglobulin (Ig) subtype or light-chain, when available. Metformin users were defined as patients that were prescribed metformin for at least 4 years, with no single break between consecutive prescriptions ≥6 months. Kaplan-Meier curves and Cox models were used to analyze the association between metformin use and the progression of MGUS to MM. Findings The analytic cohort consisted of 2,003 MGUS patients with a median follow-up time of 69 months. Within the analytic cohort, 463 metformin users (23·1%) were identified. Among the metformin users, 13 patients progressed to MM, while 74 patients progressed to MM among the non-metformin users. Metformin use was associated with a reduced risk of transformation to MM (Hazard ratio, HR: 0·47; 95% confidence interval, CI: 0·25–0·87). Interpretation For diabetics diagnosed with MGUS, metformin use for 4 years or longer was associated with a reduced risk of transformation of MGUS to MM. Prospective studies are required to determine whether this association is causal and whether these results can be extrapolated to non-diabetics.

Obesity and black race are risk factors for transformation of MGUS to MM. Future clinical trials should examine whether weight loss is a way to prevent the progression to MM in MGUS patients.

Learning Objectives Describe the association between baseline BMI, weight loss, and survival in MM. Explain the importance of BMI and baseline weight loss as part of the standard history obtained in patients with MM.