Hyperammonemia, a well-known complication of liver failure causing encephalopathy, has rarely been reported as a complication of multiple myeloma. We report four additional cases of hyperammonemia in patients with treatment refractory multiple myeloma. In these cases, we found that hyperammonemia remains a morbid complication of resistant disease without directed myeloma therapy. Our brief review has reaffirmed that hyperammonemia is a poor prognostic marker in myeloma with an undetermined mechanism. This complication’s poor response to traditional therapies, including rifaximin and lactulose, prompts our discussion urging early recognition and myeloma directed therapy. Clinical observations may support that proteasome inhibitors may be most effective in the treatment of these patients.
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