VTE Incidence in RRMM Patients Treated with NOVEL Agents: A Monocentric Real Life Experience
Authors: Giuffrida Gaetano , Conticello Concetta , Calafiore Valeria , Martino Enrica Antonia , Giamporcaro Silvia , Romano Alessandra , Di Raimondo Francesco 
Published: November 2019

INTRODUCTION: Venous thromboembolism (VTE) is very common in patients with malignancies. Compared to the general population, patients with multiple myeloma (MM) have a 9-fold increased risk of developing VTE. In patients treated with thalidomide or lenalidomide, current guidelines recommend systematic VTE prophylaxis with ASA in low risk patients while vitamin K antagonists (VKA) or low weight molecular heparin (LWMH) or unfractionated heparin (UFH) in high-risk patients, based on the type of anti-MM treatment that patients receive and patient-related individual risk factors (e. g. history of VTE). However, little is known on VTE prophylaxis in patients treated with next generation anti-myeloma drugs, such as pomalidomide, carfilzomib and monoclonal antibodies daratumumab and elotuzumab.
Here, we describe the incidence of VTE in MM patients treated with third generation novel agents in real life. In addition, we stratify patients on drugs category-based regimens to evaluate strategy of VTE prophylaxis between different groups of patients.
MATERIALS AND METHODS: A retrospective cohort of 137 patients affected by relapsed and/ or refractory multiple myeloma treated with novel agents was analyzed. Patients were followed at the Division of Hematology of Catania from April 2013 to June2019.
Our series includes 75 patients exposed to Pomalidomide and Dexametasone (PomaD), 46 patients receiving Carfilzomib, Lenalidomide and desamethasone regimen (KRd), 14 patients exposed to Daratumumab(Dara), 27 patients to Daratumumab, Bortezomib and desamethasone (DaraVD), 4 patients to Daratumumab lenalidomide and desamethasone (DaraRd), and12 patients exposed to Elotuzumab and Lenalidomide (EloRd). Several patients were exposed to multiple lines of treatment with novel agents: the total number of analyzed treatments are 178.
Patients were stratified to high or low risk for VTE: risk factors taken into account were obesity, history of VTE, central venous catheter, inhered thrombophilia, surgical procedures and comorbidities such as infections, immobilization, cardiac disease, chronic renal disease. Low risk patients had no or one risk factor; in case of two or more risk factors, the patients were classified as high risk.
Low-dose aspirin (ASA 100 mg per os once daily) or equivalent was prescribed in low risk patients, low-molecular-weight heparin (LMWH) or equivalent was given to high risk patients. Only Dara treatment did not include standard prophylaxis in patients without risk factors.
RESULTS: Real life observation revealed a low incidence of VTE (6 VTE-4,3%) in patients exposed to novel agents together with a standard prophylaxis in case of risk of thromboembolic complications.
Forty patients were at high risk of VTE, while 97 patients were classified as low risk; VTE/PE occurred in 2 high risk patients who refused to make correct LMWH prophylaxis due to the discomfort of the subcutaneous administration, developing distal DVT respectively after cycle 1 and 2 of KRd.
Two low risk patients treated with PomaD developed DVT of lower extremities during cycle 2 and 4; 2 low risk patients had pulmonary embolism during PomaD cycle 8.
CONCLUSIONS: Low incidence of VTE in patients with RRMM receiving PomaD, KRd, EloRd, DaraVD, DaraRd, Dara or EloRd treatment is probably due to a correct risk assessment and subsequent prophylaxis in case of therapies including immunomodulators or in case of patients with high risk for thromboembolic complications.
These data support the use of VTE risk stratification-based prophylactic strategies in myeloma patients treated with new drugs.

Disclosures
Conticello: Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding. Di Raimondo:Takeda: Consultancy; Amgen: Consultancy, Honoraria, Research Funding.