Thrombin generation in newly diagnosed multiple myeloma during the first three cycles of treatment: An observational cohort study

Abstract

BackgroundMultiple myeloma (MM) is associated with a high risk of thrombosis, particularly during the first months of treatment including immunomodulatory drugs (IMiDs). There is no consensus on prevention of thromboembolic risk in patients with de novo MM, and identification of patients requiring anticoagulant thromboprophylaxis remains challenging. Evaluating coagulability by an in vitro thrombin generation (TG) test might be a way of identifying such patients.ObjectiveTo determine whether TG assessment could reveal an increase in coagulability during the first three chemotherapy cycles.MethodsThis prospective and longitudinal observational study included patients newly diagnosed with MM. TG was determined in platelet‐rich and platelet‐poor plasma using calibrated automated thrombography with a low tissue factor (TF) concentration.ResultsSeventy‐one patients were enrolled, allowing TG analysis during 213 chemotherapy cycles. TG remained unchanged throughout follow‐up irrespective of treatment regimen, but values determined before cycles 2 and 3 were significantly higher in patients receiving iMiDs‐containing regimens. No association was found between TG and its changes and thrombosis occurrence during follow‐up: venous thrombosis in eight patients; no cardiovascular event. A significantly (87%) lower risk of venous thrombosis was observed in patients receiving prophylaxis with a low‐molecular‐weight heparin (LMWH; OR: 0.13 (95% CI: 0.02‐0.76). Neither bortezomib‐ nor dexamethasone‐containing regimens were associated with thrombotic risk. Changes in TG, as studied, were not associated with thrombotic events.ConclusionsThe only factor associated with a reduction in early thrombotic risk was prophylaxis with LMWH. The issue of how to identify patients requiring prophylactic anticoagulation remains unresolved.

Prediction of venous thromboembolism in patients with multiple myeloma treated with lenalidomide, bortezomib, dexamethasone, and transplantation: Lessons from the substudy of IFM/DFCI 2009 cohort

“…Moreover, our incidence is lower than that observed in the Covut et al study (10.7% [95% CI: 8.2–13.2%]), but only 2.6% of their patients received heparin as prophylaxis 3 . Previous studies suggesting that bortezomib might have a protective effect are challenged by recent epidemiological literature as well as our results, 17–19 and by recent pathophysiological literature 20 . In the Ghansah et al study, bortezomib induced a procoagulant platelet phenotype even in an experimental setting devoid of plasma proteins 20 .…”

“…High incidence of AT events was suspected in MM patients, although little was known about the underlying mechanisms 21 . In our study, AT incidence at 6 months was low (1.2% [95% CI: 0.5–2.5%]) as in recent studies 9,18 . MM treatment was delayed in one third of patients experiencing VTE.…”

“…The size of the IFM2009 cohort versus the two randomized studies (700 vs. 342 and 445 patients) could explain, at least in part, the significant effect of LMWH observed in our study. 8,9,18 Our VTE risk is quite similar compared to primary thromboprophylaxis in ambulatory cancer patients receiving chemotherapy, with a 4.4% reported incidence of VTE with LMWH versus 7.1% with no thromboprophylaxis. 37 So, heparin prophylaxis failure is similar in nMM and other patients with cancer.…”

Multiple Myeloma and Thrombosis: Prophylaxis and Risk Prediction Tools

“…TG parameters remained unchanged throughout treatment irrespective of treatment regimen, but they were significantly higher before cycles 2 and 3 for patients who received IMiDs. No association was determined between baseline levels of ETP, thrombin peak concentration, or time to peak and VTE [29]. In another study of 106 MM patients, the TG capacity was higher in MM patients both in platelet-poor plasma (PPP) and platelet-rich plasma (PRP).…”

Effect of heparin thromboprophylaxis on thrombin generation in multiple myeloma patients

“…Therefore, our study found no evidence for an in vitro LMWH specific resistance in MM patients depending on their intrinsic VTE risk compared with other haematological malignancies or medical patients, even though our MM patients were known to have a high‐VTE risk because of their treatments. Indeed, it was demonstrated that MM patients treated with immunomodulatory drugs have a higher VTE risk and higher TGT level than other patients with MM (Chalayer et al , ). Our patients with lymphoma present similar results although they do not seem to be at high VTE risk: the median Korana score, recently validated by Parker et al () in in‐hospital VTE development in cancer, was 1.…”