Between 20% and 40% of patients with multiple myeloma (MM) have renal impairment and also may take drugs that raise the risk of venous thromboembolism (VTE). Do those factors contribute to a higher risk of arterial thrombosis in this patient group? Researchers from the University of Arkansas and Ohio State University conducted a large, retrospective, comparative case control study to find out.
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Patients were enrolled in Total Therapy protocols (TT2, TT3a, and TT3b), which tested varying combinations of thalidomide, bortezomib, lenalidomide, and dexamethasone. Of 1,148 patients, 46 (4%) had strokes, usually ischemic stroke (33 patients, or 72%). Hypercoagulability, atrial fibrillation and small-vessel occlusion were common mechanisms. Whereas other research has found a higher risk of arterial thrombosis from activated prothrombotic factors, especially during the early period of chemotherapy, in this study vascular events occurred months later.
Seven patients died in the hospital (15% compared with a national average of 5%). Although 6 of those deaths were stroke related, 36 patients were discharged home or to a rehabilitation facility; 2 were discharged to a long-term nursing facility. During a median follow-up of 10 years, 6 patients had another stroke. The cumulative risk of recurrent stroke was 15% compared with 5% for the general population.
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Stage I and II cancers and renal insufficiency independently predicted stroke. Also noteworthy, according to the researchers: Patients with MM who developed renal insufficiency had worse clinical outcomes despite improvement in their renal function or lack of significant difference in their baseline renal functions between various treatment protocols. Thus, the increased risk of stroke, recurrent stroke, and mortality could partly be due to renal disease, which may or may not have resulted from myeloma.
Use of combination chemotherapy has “markedly improved” clinical outcomes for MM patients, the researchers say, but those drugs have also been associated with an increased risk of VTE, especially during the first months of chemotherapy. Thalidomide alone did not increase the risk of VTE, nor did lenalinomide on its own. However, thalidomide combined with multiagent chemotherapy increased VTE risk as much as 34% in newly diagnosed patients, and lenalinomide with dexamethasone boosted risk as high as 75%.
The researchers found no significant relationship between mortality and use of thalidomide. Median survival was 103 months for a thalidomide-based regimen and 78 months for a regimen without thalidomide.
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The researchers noted that the patients developed strokes despite a trend toward coagulopathy, to the extent that half were ineligible for immediate use of antiplatelet agents. The study findings “heightened our awareness,” the researchers say, that aggressive preventive measures can help reduce the incidence of stroke in patients with renal insufficiency.
Source:
Hinduja A, Limaye K, Ravilla R, et al. PLoS One. 2016;11(11): e0166627.
doi: 10.1371/journal.pone.0166627.