High-Risk and Smoldering Multiple Myeloma

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Myeloma is often diagnosed after a patient presents with abnormalities in laboratory testing results. Noopur Raje, MD, and Sagar Lonial, MD, state that additional testing can help clinicians better evaluate the extent of bone disease and differentiate between active or smoldering myeloma. Lonial explains that PET/CT scans can offer insight on the presence or absence of bone disease, and if bone disease is present, the extent of disease activity. In the clinical trial setting, immunepheresis may be used to determine whether a patient has high-risk smoldering myeloma, notes Raje.

There is a need for better diagnostic criteria and a standard threshold for high-risk smoldering myeloma, according to Lonial and Raje. Based on currently used definitions of myeloma, a subgroup of patients exists who do not satisfy the criteria for diagnosis of myeloma but who have a high risk of developing end-organ damage within a year, comments Lonial. Researchers are currently evaluating the use of certain tests (eg, serum free light chain ratio, cytogenetics in the abnormal clone) to help identify features that put patients in the high risk category, notes Raje. Hopefully, new guidelines from the International Myeloma Working Group will provide clarification regarding the diagnosis of myeloma.

Treatment varies depending on the stage of myeloma, and both Raje and Lonial state that patients who present with symptoms of CRAB (hypercalcemia, renal insufficiency, anemia, or bone disease) usually have symptomatic myeloma and should receive treatment. However, for patients with smoldering myeloma, Raje and Lonial note that the current standard of care is observation.

Lonial is currently overseeing a clinical trial that compares therapy with lenalidomide versus observation in patients with intermediate or high-risk smoldering myeloma. Raje describes a recent trial that evaluated lenalidomide plus dexamethasone versus observation in patients with high-risk smoldering myeloma. The results showed longer progression-free survival in patients who received lenalidomide plus dexamethasone compared with observation. Raje is also currently investigating the use of a tripeptide vaccine (PVX-410) at his clinical practice site. Additionally, Raje notes that many researchers are interested in identifying the patient population with high-risk smoldering myeloma; some researchers believe that high-risk smoldering myeloma is actually very early multiple myeloma.