Efficacy and Safety of Rivaroxaban As Thromboprophylaxis in Newly Diagnosed Multiple Myeloma Patients Receiving Immunomodulatory and Dexamethasone Based Treatment: Comorbidities Risk Adapted Score

The risk for venous thromboembolism (VTE) is high patients with multiple myeloma (MM) receiving thalidomide or lenalidomide with dexamethasone based induction treatment (IMiDs-Dex), especially in the first 6 months. There are multiple scores for risk stratification (IMPEDE and SAVED for example), that give different points for the same variable and can be classified in low or high risk depending which is used, the same patient can receive Aspirin in one score or LMWH in the other. In our country, Mexico, the prevalence of overweight and obesity is 75.2%, hypertension 49.4% and diabetes 16.8% (Salud Publica Mex 2021;63:692-704); factors that contribute to develop VTE. In 2018 we reported the use of Aspirin or Rivaroxaban in low risk patient with DM or obesity: could be intermediate risk (Blood 2018;132:5068); since then we adapted a risk score based in the high prevalence comorbidities of our population.

From January 2018 to December 2022, 117 patients were diagnosed with active MM and 109 patients that received IMiDs-Dex based triplet induction and maintenance with IMiDs were eligibles for study. Patients were assigned into three groups for prophylaxis: a) low risk (treatment only) Aspirin 100 mg daily, b) intermediate risk (treatment and one from overweight or obesity, hypertension and diabetes) randomized 1:1 to Aspirin 100 mg or Rivaroxaban 10 mg daily, c) high risk (treatment and 2 or 3 from overweight or obesity, hypertension and diabetes; or treatment and another known high risk) Rivaroxaban 10 mg daily. Lower limbs doppler ultrasound was performed every two months or as medical indication, pulmonary CT scan if pulmonary embolism was suspected.

Twenty-three patients (21.1%) had low risk and received Aspirin, one patient developed DVT from right lower limb, she received anticoagulation with Rivaroxaban for 6 months and then placed in prophylactic dose, no further DVT developed. Thirty-eight patients (34.9%) had intermediate risk; 19 received Aspirin, one patient developed DVT with pulmonary embolism and received anticoagulation with Rivaroxaban for 6 months and then placed in prophylactic dose, no further thrombosis developed; 19 received Rivaroxaban, no patient developed thrombosis. Forty-eight patients (44.0%) had high risk and received Rivaroxaban; two patients developed DVT, none with pulmonary embolism, both with more than four risk factors, they received anticoagulation with Rivaroxaban for 6 months and then placed in prophylactic dose, no further thrombosis developed. In all groups less than 5 percent of patients had easy bruising and mild epistaxis or gingivorrhagia that no required hold of dose; no major bleeding was detected.

In low risk patients that received Aspirin, 4.34% developed DVT; the change to Rivaroxaban was beneficial as no further thrombosis developed. In intermediate risk, 2.6% developed DVT-PE in the Aspirin arm and none in the Rivaroxaban, demonstrating the efficacy of Rivaroxaban. In the high risk patients all received Rivaroxaban, 4.16% developed DVT, similar result as Aspirin in the low risk patients, but the patients had more than four risk factors, that could be a very high group and a more intense prophylactic or complete anticoagulation is advised; in high risk patients with less than three factors Rivaroxaban is effective in preventing thrombosis episodes. The safety of Rivaroxaban is demonstrating again, as the bleeding in both groups were similar. An external cohort is needed to validate our results and this comorbidity risk adapted score can be national and international-wide used, as the prevalence of overweight or obesity, hypertension and diabetes are high among occidental countries, especially Mexico, as they impact in the morbidity and mortality not only in neoplastic diseases (Arch Med Res 2022;53:100-108) . A very high risk patients group will be considered for Rivaroxaban in dose of 15 or 20 mg in following studies. As a final statement, these results complement our first report and give more solid evidence in the efficacy and safety of Rivaroxaban as thromboprophylaxis in Multiple Myeloma patients with IMiDs-Dex based triplet induction and maintenance with IMiDs.