Prophylactic Low-Dose Aspirin Is Effective as Antithrombotic Therapy in Patients Receiving Combination Thalidomide or Lenalidomide.

Introduction: Thalidomide and the IMiDs are rapidly becoming mainstays in the treatment of multiple myeloma. To improve the efficacy of thalidomide (T) or Revlimid (lenalidomide) (R), we have developed the BLT-D (Biaxin® (clarithromycin) (B), low dose T, and dexamethasone (D)), and the BiRD (B, R, D) regimens. These regimens have produced remarkably high responses, including complete and near complete remissions, with almost every patient not previously exposed to thalidomide. When the BLT-D regimen was initiated, an excessive number of thrombotic episodes were noted. Subsequent to this initial observation, others have also reported an inordinate number of thrombotic events, usually when T was combined with other biological or chemotherapy agents. Given the putative antiangiogenic properties of T or R, we postulated that endothelial damage may be responsible for the enhanced thrombosis and thus, subsequently initiated low dose aspirin (ASA), 81mgs, as prophylaxis in patients (pts) undergoing treatment. We report the effect of low dose ASA as a prophylactic treatment when given to pts receiving L/T containing regimens as follows:

1. A retrospective analysis of pts receiving BLT-D before ASA prophylaxis compared to a similar group after ASA was instituted;

2. An examination of the incidence of thromboembolic phenomena in pts receiving either D alone, not receiving ASA, compared to combined D and low dose T, receiving ASA, as part of a prospective sequential randomized study also studying the impact of subsequent B and 3) An evaluation of thrombosis in pts receiving the BiRD regimen with mandated low dose ASA.

Results:

1. Low dose ASA significantly reduced the incidence of thrombosis in pts receiving BLT-D. Of the 60 pts studied, 5 (8%) developed grade 1–2 thrombosis, primarily thrombophlebitis (DVT), and 9 pts (15%) developed grade ≥3 thrombosis, primarily pulmonary embolism (PE) and coronary thrombosis. All episodes of thrombosis occurred prior to the institution of ASA.

2. Slightly less thrombotic events were recorded in pts receiving low dose ASA and the T-D combination with or without B (1/12) when compared to pts not receiving ASA and D with or without B (3/11). 3) Three of 22 pts treated with the BiRD regimen have developed thromboembolic complications, all while off the prescribed ASA. Patient 1, a 44 yo male discontinued (d/c’ed) ASA due to epistaxis. Exactly 7 days after d/c’ing ASA, and while remaining on BiRD, he developed a DVT and PE. Patient 2 underwent exploratory laparotomy to investigate a renal mass. ASA and BiRD were discontinued 7 days prior to surgery. Ten days after surgery, the patient developed DVT. Patient 3 underwent closure of a colostomy; ASA and BiRD were d/c’ed 7 days prior surgery. Two days after the surgery, despite low dose heparin, he suffered a fatal massive PE. No thrombotic episodes with BiRD have not occurred with pts remaining on ASA.

Conclusions: Low dose ASA appears to reduce the incidence of thrombosis in pts receiving combination T or R therapy. Endothelial damage may persist beyond the residual salutary effects of discontinued ASA.