Thalidomide (THAL) and Lenalidomide (LEN)-Associated Venous Thromboembolism (VTE): Optimal Prophylaxis Strategies Remain Elusive

Thalidomide (THAL) and lenalidomide (LEN) are established treatments for multiple myeloma (MM), often in combination with other drugs. Venous thromboembolism (VTE) is a common feature of therapy as evidenced by a Boxed warning to package inserts for both drugs when administered to MM patients. Oncologists are encouraged to consider VTE prophylaxis even though optimal strategies for prophylaxis remain mostly elusive. We sought to (1) determine the prevalence of VTE events among in-patients receiving THAL or LEN at a tertiary academic medical center and (2) to determine whether patients receiving concomitant VTE prophylaxis therapies (aspirin, heparin, low molecular heparin or other oral anticoagulants) have lower rates of VTE events. After obtaining Institutional Review Board approval we completed an extensive retrospective chart review.

We abstracted data from de-identified pharmacy records connected to charts of in-patients with MM who were treated with THAL or LEN (N=102) by every hematologist on staff; we excluded redundant charts (N=11), analyzing the remaining charts (N=91). A syndrome specific case report form developed by the Principal Investigator was used to collect data. General Demographic information, adverse drug events (ADE), response to ADE, treating physicians' assessment, disease and general ADE outcomes, and causality were recorded. Data were analyzed statistically using Chi square and comparison of demographic variables was done using the Fisher's exact t-test. Kaplan-Meier curve was applied to survival data.

Total time on THAL (N=69; median=12 days, range=0–1098 days); total time on LEN (N=40; median=14.5 days, range=0–731 days); VTE rate for THAL was 25%; LEN was 26.67%; both were 41.67%, p=0.30. All pts received heparin; 1 received LMWH. For Epo alpha, VTE rate was 30.00% in those who did not receive EPO and 35.48% in those who did; p=0.64. For Coumadin, 25.71% who did not receive coumadin suffered VTE while 52.38% on Coumadin did not, p=0.032. For ASA, 33.33% pt who did take ASA experienced a PE while 26.32% of those on ASA did not; p=0.78. For lovenox VTE occurred in 33.33% of patients not on lovenox while 29.41% of those on lovenox had no VTE, p=0.82. Overall, 22 patients experienced VTE (8 on LEN and 14 on THAL). If there was an adverse event, the drug was discontinued. Follow-up time was a median of 11.2 months (range.07 – 115months). Kaplan-Meier curve for overall survival (OS) revealed that 31/91 persons died; 1 year OS was 70%, 2 year OS was 62%, and 5 year OS 50%; Kaplan-Meier curve for VTE-free survival revealed 25/87 persons with VTE, 1 year VTE-free survival was 73%, 2 year VTE-free survival was 64%, 5 year VTE-free survival was 64%.

VTE rates were high in our study and mirrors rates reported in other studies. Optimal VTE prophylaxis strategies for MM patients who receive LEN or THAL remain elusive. Providers are encouraged to use at least one of the standard oral or subcutaneous anti-coagulants. A formal randomized trial of alternative VTE strategies is needed.

No relevant conflicts of interest to declare.