Clinical Outcomes of Multiple Myeloma Patients Treated with Direct Oral Anticoagulants for Immunomodulatory Drug Associated Venous Thromboembolism
Authors: Crowther Zachary , Doyle Jamie , Taylor Stanford , Ali Nadia 
Published: November 2019

Introduction:
Venous thromboembolism (VTE) is a common complication in multiple myeloma (MM) patients for several reasons; hematologic malignancy itself is a VTE risk factor and standard of care immunomodulatory drugs (IMiDs) in combination with dexamethasone (Dex) increase the risk further. This combination therapy has a mean VTE incidence of 21.5% in studies that did not use thromboprophylaxis and is recommended for all patients on IMiDs, although the optimal thromboprophylactic regimen remains uncertain. In clinical practice, aspirin (ASA) is commonly prescribed for VTE prophylaxis due to the ease of use. Despite this, the incidence of VTE remains between 7-14%. There is a growing body of literature supporting the efficacy and safety of direct oral anticoagulants (DOACs) for the treatment of VTE in cancer populations. We wanted to assess the incidence of VTE despite ASA prophylaxis at our institution and to further characterize the role of DOACs in the MM population. To do this, we performed a chart review of all MM patients who had been treated with lenalidomide and a DOAC, assessing for VTE development and patient outcomes.
Methods:
We conducted a retrospective chart review of patients with the diagnosis of MM treated with lenalidomide therapy at Fox Chase Cancer Center at Temple University Hospital or Cottman Avenue after Jan 1st, 2015 to July 2019. Eligible patients were identified through electronic medical record data mining for patients that had been diagnosed with MM, had been prescribed lenalidomide, had been taking ASA while on lenalidomide, and switched to rivaroxaban, edoxaban or apixaban. For comparison, the number of patients treated with lenalidomide and ASA who did not switch to a DOAC were also identified. Patient charts were reviewed for VTE development and bleeding complications after DOAC administration.
Results:
132 patients were identified who had a diagnosis of MM and had been prescribed lenalidomide between Jan 1, 2015 and July 31, 2019. These patients were also prescribed aspirin except for three who were already on a DOAC prior to starting lenalidomide. Of the total 132 patients, only 17 were prescribed a DOAC. Six of the patients were on DOACs for reasons other than VTE (atrial fibrillation N=4, atrial flutter N=1, marantic endocarditis N=1). Eleven patients were started on DOACs for VTE; incidence of 8.3% in our myeloma population. However three of these VTEs occurred within one month of high dose melphalan chemotherapy and autologous stem cell rescue. These three patients had been off lenalidomide for over one month prior to VTE. Eight of the 17 patients with VTE developed clots in the setting of active MM and concurrent therapy with IMiD/Dex, independent of hospitalizations or other provoking factors. This is an incidence of 6.0% for VTE directly attributed to therapy. Six patients were on lenalidomide and Dex, while two patients developed VTE while on pomalidomide and Dex. No patients on lenalidomide experienced recurrent VTEs after being switched to therapeutic dose DOAC. One patient on pomalidomide/Dex did experience recurrent VTE. We examined all 17 patients who were on DOACs, 16 of which had been on IMiD and DOACs concurrently. Three had minor bleeding events which all resolved spontaneously. One patient had a major bleeding event, which was a fatal ruptured cerebral aneurysm while on a DOAC and ASA concurrently.
Conclusion:
The incidence of VTE in our patient population receiving IMiD/Dex while on ASA prophylaxis therapy was similar to what has been previously reported in the literature. We examined the clinical outcomes of 16 patients treated with IMiDs and DOACs concurrently and found few bleeding events. The one major bleed was likely precipitated by malignant hypertension and not a direct result of being on a DOAC. Taken together these results further support the growing body of evidence that DOACs are effective and safe treatments for VTE in cancer patients, including MM. Moving forward, our clinical experience with treatment dose DOACs supports the use of prophylactic dose DOACs to potentially further reduce the incidence of VTE in this high-risk population.

Disclosures
No relevant conflicts of interest to declare.