Multiple Myeloma: Updates on Diagnosis and Management

Multiple myeloma (MM) is a disease that is primarily treated by hematologists; however, it is important for primary care providers (PCPs) to be aware of the presentation and diagnosis of this disease. Multiple myeloma often is seen in the veteran population, and VA providers should be familiar with its diagnosis and treatment so that an appropriate referral can be made. Often, the initial signs and symptoms of the disease are subtle and require an astute eye by the PCP to diagnose and initiate a workup.

Once a veteran has an established diagnosis of MM or one of its precursor syndromes, the PCP will invariably be alerted to an adverse event (AE) of treatment or complication of the disease and should be aware of such complications to assist in management or referral. Patients with MM may achieve long-term remission; therefore, it is likely that the PCP will see an evolution in their treatment and care. Last, PCPs and patients often have a close relationship, and patients expect the PCP to understand their diagnosis and treatment plan.

Presentation

Multiple myeloma is a disease in which a neoplastic proliferation of plasma cells produces a monoclonal immunoglobulin. It is almost invariably preceded by premalignant stages of monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM (SMM), although not all cases of MGUS will eventually progress to MM. ¹ Common signs and symptoms include anemia, bone pain or lytic lesions on X-ray, kidney injury, fatigue, hypercalcemia, and weight loss. ² Anemia is usually a normocytic, normochromic anemia and can be due to involvement of the bone marrow, secondary to renal disease, or it may be dilutional, related to a high monoclonal protein (M protein) level.
There are several identifiable causes for renal disease in patients with MM, including light chain cast nephropathy, hypercalcemia, light chain amyloidosis, and light chain deposition disease. Without intervention, progressive renal damage may occur. ³

Diagnosis

All patients with a suspected diagnosis of MM should undergo a basic workup, including complete blood count; peripheral blood smear; complete chemistry panel, including calcium and albumin; serum free light chain analysis (FLC); serum protein electrophoresis (SPEP) and immunofixation; urinalysis; 24-hour urine collection for electrophoresis (UPEP) and immunofixation; serum B2-microglobulin; and lactate dehydrogenase. ⁴ A FLC analysis is particularly useful for the diagnosis and monitoring of MM, when only small amounts of M protein are secreted into the serum/urine or for nonsecretory myeloma, as well as for light-chainonly myeloma. ⁵

A bone marrow biopsy and aspirate should be performed in the diagnosis of MM to evaluate the bone marrow involvement and genetic abnormality of myeloma cells with fluorescence in situ hybridization (FISH) and cytogenetics, both of which are very important in risk stratification and for treatment planning. A skeletal survey is also typically performed to look for bone lesions. ⁴ Magnetic resonance imaging (MRI) can also be useful to evaluate for possible soft tissue lesions when a bone survey is negative, or to evaluate for spinal cord compression. ⁵ Additionally, an MRI should be performed in patients with SMM at the initial assessment, because focal lesions in the setting of SMM are associated with an increased risk to progression. ⁶ Since plain radiographs are usually abnormal only after ≥ 30% of the bone is destroyed, an MRI offers a more sensitive image.