Prophylactic low-dose aspirin is effective antithrombotic therapy for combination treatments of thalidomide or lenalidomide in myeloma

Abstract

Multiple myeloma (MM) patients have a propensity for thromboembolic events (TE), and treatment with thalidomide/dexamethasone or lenalidomide/dexamethasone increases this risk. This report describes the use of low-dose aspirin (81 mg) as primary thromboprophylaxis in three series of MM patients receiving thalidomide or lenalidomide with other drugs. In the first regimen (clarithromycin, thalidomide, dexamethasone), initiation of low-dose aspirin negated the occurrence of any further TE. In a second study, prophylactic aspirin given with thalidomide/dexamethasone resulted in a rate of TE similar to that seen with dexamethasone alone (without aspirin). A third study (n = 72) evaluated thrombosis rates with aspirin and a lenalidomide-containing regimen (clarithromycin, lenalidomide, dexamethasone). Of nine occurrences of thromboembolism, five were associated with aspirin interruption or poor compliance. Low-dose aspirin appears to reduce the incidence of thrombosis with these regimens. Routine use of aspirin as antithrombotic prophylaxis in MM patients receiving immunomodulatory drugs with corticosteroids is warranted.

BiRD (Biaxin [clarithromycin]/Revlimid [lenalidomide]/dexamethasone) combination therapy results in high complete- and overall-response rates in treatment-naive symptomatic multiple myeloma.

“…These results underscore the critical importance of thromboprophylaxis both during and for at least 10 days after BiRD treatment. [40][41][42] The results of this study support further exploration of BiRD for induction therapy, because it produces high RRs and may increase disease-free and overall survival when used in conjunction with autologous transplantation. In addition, prolonged use of BiRD with judicious corticosteroid dose modifications may be a reasonable option for the treatment of older patients ineligible for aggressive consolidation strategies.…”

Absence of tissue factor expression by neoplastic plasma cells in multiple myeloma

“…Furthermore, a puzzling clinical observation has been that thrombosis in the context of IMID-based therapy may be prevented by the use of prophylactic aspirin. 10 Here, we sought to study the gene expression status of F3 (encoding the TF protein) by microarray analysis in human myeloma cell lines (HMCL) and bone marrow from MM patients, as well as the TF protein expression in myeloma plasma cells in bone marrow biopsies, and to compare the results with solid tumor cell lines.…”

Novel agents in myeloma: An exciting saga

“…This is notwithstanding the reported lack of efficacy of aspirin in 'slow flow' venous thrombosis, a frequently reported phenomenon with thalidomide-dexamethasone. 17 Heparin and warfarin have also been effective prophylactics for venous thrombosis in MM therapy, but low-dose warfarin may not be adequate. 18 As a natural sequence in testing, the Eastern Cooperative Oncology Group (ECOG) headed up a cooperative group study pitting thalidomide and dexamethasone in a randomized trial against dexamethasone alone in newly diagnosed patients destined for ASCT.…”

“…Apparently, any putative damage to the endothelium is more long-standing that the antithrombotic effects of aspirin, for instance, which usually abates in approximately 10 days. 17 Bortezomib, another novel agent, entered the market in 2003 with a mechanism of action believed to be entirely different from the IMiDs. The major activity of bortezomib is inhibition of proteasome activity.…”

“…Does the patient have a thrombotic tendency, renal failure, a poor prognostic FISH abnormality, a venous access problem, a neuropathy, or limited bone marrow reserve? 17,35,53 In each of the aforementioned presentations, 1 novel agent over the other would be selected depending on the expected side effect profile (tolerability) of the chosen regimen. The lack of randomized clinical trials pitting 1 novel therapy versus another, or against ASCT, makes it difficult to point to any 1 agent, regimen, or modality as reigning supreme.…”