Improving VTE Risk Prediction for Patients With Multiple Myeloma

Although patients with multiple myeloma (MM) have an increased risk of developing venous thromboembolism (VTE), no validated model exists that predicts VTE in MM. To help health care providers better assess the risks and the appropriateness of thromboprophylaxis, a team of researchers have developed the IMPEDE VTE risk assessment tool.

According to Kristen M. Sanfilippo, MD, of Washington University School of Medicine and the St. Louis Veterans Affairs Medical Center in Missouri, who presented the paper at the American Society of Hematology meeting last week in San Diego, this is the first effort to build a tool that is both internally and externally validated. The goal was to develop a model that outperformed current National Comprehensive Cancer Network (NCCN) guidelines for VTE that are based on expert opinion and were not specific to patients with multiple myeloma.

“We evaluated the performance of the current NCCN and International Myeloma Working Group guidelines with the VA data and our model outperformed these guidelines. Our recommendations is that our IMPEDE VTE should be considered to replace them,” said Sanfilippo. "I think we can improve our predictability of thrombosis in myeloma by adding novel predictors to the model, but that would have to be assessed in a prospective manner.”

Using the VA Central Cancer Registry, the researchers identified 4,448 patients diagnosed with MM between 1999 and 2014 and retrospectively followed the patients for 180 days after start of MM chemotherapy. Using beta coefficients, the researchers developed a risk score by dividing by a common divisor and rounding to the nearest integer. The risk score for each patient was the sum of all scores for each predictor variable.

The factors associated with VTE were combined to develop the IMPEDE VTE score. The factors were: Immunomodulatory drugs, 3 points; BMI > 25,  1 point; Pathologic fracture pelvis/femur 2 points; Erythropoiesis-stimulating agents, 1 point, Dexamethasone (High-dose 4 points; low-dose 2 points)/Doxorubicin 2 points; Asian Ethnicity, -3 points; history of VTE, 3 points; Tunneled line/ central venous catheter, 2 points). In addition, use of therapeutic anticoagulation (-5 points) with warfarin or low molecular weight heparin (LWMH) and use of prophylactic LMWH or aspirin (-2 points) were associated with a decreased risk of VTE. The risk score then identifies patients’ VTE risk as low (≤ 3), intermediate (4-6), or high (≥ 7).

According to Sanfilippo, the model showed satisfactory discrimination in both the derivation cohort (Harrell’s c-statistic = 0.66) and in the bootstrap validation, c-statistic = 0.66 (95% CI: 0.63 – 0.70). Within the first 6-months of starting chemotherapy, the rate of VTE was 3.5% compared to > 10% for high-risk patients.

The researchers hoped that the risk prediction model for VTE in MM would allow for use of thromboprophylaxis in MM patients at high-risk of VTE while sparing those at low risk. 

Although patients with multiple myeloma (MM) have an increased risk of developing venous thromboembolism (VTE), no validated model exists that predicts VTE in MM. To help health care providers better assess the risks and the appropriateness of thromboprophylaxis, a team of researchers have developed the IMPEDE VTE risk assessment tool.

According to Kristen M. Sanfilippo, MD, of Washington University School of Medicine and the St. Louis Veterans Affairs Medical Center in Missouri, who presented the paper at the American Society of Hematology meeting last week in San Diego, this is the first effort to build a tool that is both internally and externally validated. The goal was to develop a model that outperformed current National Comprehensive Cancer Network (NCCN) guidelines for VTE that are based on expert opinion and were not specific to patients with multiple myeloma.

“We evaluated the performance of the current NCCN and International Myeloma Working Group guidelines with the VA data and our model outperformed these guidelines. Our recommendations is that our IMPEDE VTE should be considered to replace them,” said Sanfilippo. "I think we can improve our predictability of thrombosis in myeloma by adding novel predictors to the model, but that would have to be assessed in a prospective manner.”

Using the VA Central Cancer Registry, the researchers identified 4,448 patients diagnosed with MM between 1999 and 2014 and retrospectively followed the patients for 180 days after start of MM chemotherapy. Using beta coefficients, the researchers developed a risk score by dividing by a common divisor and rounding to the nearest integer. The risk score for each patient was the sum of all scores for each predictor variable.

The factors associated with VTE were combined to develop the IMPEDE VTE score. The factors were: Immunomodulatory drugs, 3 points; BMI > 25,  1 point; Pathologic fracture pelvis/femur 2 points; Erythropoiesis-stimulating agents, 1 point, Dexamethasone (High-dose 4 points; low-dose 2 points)/Doxorubicin 2 points; Asian Ethnicity, -3 points; history of VTE, 3 points; Tunneled line/ central venous catheter, 2 points). In addition, use of therapeutic anticoagulation (-5 points) with warfarin or low molecular weight heparin (LWMH) and use of prophylactic LMWH or aspirin (-2 points) were associated with a decreased risk of VTE. The risk score then identifies patients’ VTE risk as low (≤ 3), intermediate (4-6), or high (≥ 7).

According to Sanfilippo, the model showed satisfactory discrimination in both the derivation cohort (Harrell’s c-statistic = 0.66) and in the bootstrap validation, c-statistic = 0.66 (95% CI: 0.63 – 0.70). Within the first 6-months of starting chemotherapy, the rate of VTE was 3.5% compared to > 10% for high-risk patients.

The researchers hoped that the risk prediction model for VTE in MM would allow for use of thromboprophylaxis in MM patients at high-risk of VTE while sparing those at low risk. 

Although patients with multiple myeloma (MM) have an increased risk of developing venous thromboembolism (VTE), no validated model exists that predicts VTE in MM. To help health care providers better assess the risks and the appropriateness of thromboprophylaxis, a team of researchers have developed the IMPEDE VTE risk assessment tool.

According to Kristen M. Sanfilippo, MD, of Washington University School of Medicine and the St. Louis Veterans Affairs Medical Center in Missouri, who presented the paper at the American Society of Hematology meeting last week in San Diego, this is the first effort to build a tool that is both internally and externally validated. The goal was to develop a model that outperformed current National Comprehensive Cancer Network (NCCN) guidelines for VTE that are based on expert opinion and were not specific to patients with multiple myeloma.

“We evaluated the performance of the current NCCN and International Myeloma Working Group guidelines with the VA data and our model outperformed these guidelines. Our recommendations is that our IMPEDE VTE should be considered to replace them,” said Sanfilippo. "I think we can improve our predictability of thrombosis in myeloma by adding novel predictors to the model, but that would have to be assessed in a prospective manner.”

Using the VA Central Cancer Registry, the researchers identified 4,448 patients diagnosed with MM between 1999 and 2014 and retrospectively followed the patients for 180 days after start of MM chemotherapy. Using beta coefficients, the researchers developed a risk score by dividing by a common divisor and rounding to the nearest integer. The risk score for each patient was the sum of all scores for each predictor variable.

The factors associated with VTE were combined to develop the IMPEDE VTE score. The factors were: Immunomodulatory drugs, 3 points; BMI > 25,  1 point; Pathologic fracture pelvis/femur 2 points; Erythropoiesis-stimulating agents, 1 point, Dexamethasone (High-dose 4 points; low-dose 2 points)/Doxorubicin 2 points; Asian Ethnicity, -3 points; history of VTE, 3 points; Tunneled line/ central venous catheter, 2 points). In addition, use of therapeutic anticoagulation (-5 points) with warfarin or low molecular weight heparin (LWMH) and use of prophylactic LMWH or aspirin (-2 points) were associated with a decreased risk of VTE. The risk score then identifies patients’ VTE risk as low (≤ 3), intermediate (4-6), or high (≥ 7).

According to Sanfilippo, the model showed satisfactory discrimination in both the derivation cohort (Harrell’s c-statistic = 0.66) and in the bootstrap validation, c-statistic = 0.66 (95% CI: 0.63 – 0.70). Within the first 6-months of starting chemotherapy, the rate of VTE was 3.5% compared to > 10% for high-risk patients.

The researchers hoped that the risk prediction model for VTE in MM would allow for use of thromboprophylaxis in MM patients at high-risk of VTE while sparing those at low risk.