Urgent considerations
See Differentials for more details
A small proportion of patients can present with life-threatening complications or complications that require urgent therapy to control symptoms and to avoid long-term consequences. Most of the scenarios described below occur in the context of active, symptomatic myeloma.[39]
Acute renal failure
Approximately 20% of patients with multiple myeloma have renal failure at the time of diagnosis, although patients with other monoclonal gammopathy-related disorders may also have compromised renal function at the time of diagnosis.[40][41][42] The aetiology of renal failure in this setting can be multi-factorial. The most common underlying finding is light chain cast nephropathy. Other causes of renal insufficiency in patients with a monoclonal gammopathy include hypercalcaemia, light chain deposition disease, light chain amyloidosis, hyperuricaemia, contrast dye, cryoglobulinaemic vasculitis, and the use of non-steroidal anti-inflammatory drugs (NSAIDs).
It is extremely important to identify the aetiology of renal failure to guide management.[42] In the presence of light chain cast nephropathy, patients typically have elevated serum free light chains, often above 1g/L of kappa or lambda light chains. Renal biopsy is often needed to make a definitive diagnosis and should be strongly considered once emergency therapeutic measures such as hydration and correction of electrolyte abnormalities have been instituted.[43] Specific anti-myeloma therapy with drugs such as bortezomib (a proteasome inhibitor) and/or daratumumab (a CD38 targeting monoclonal antibody) should be initiated along with corticosteroids.[44][45] The role of plasmapheresis remains controversial but is used by many clinicians, especially in the setting of high levels of serum free light chain.[46][47][48]
Other renal disorders associated with monoclonal proteins include membranoproliferative glomerulonephritis (MPGN).[49]
Hypercalcaemia
This is a common finding in myeloma and is related to the strong osteoclastic activation by myeloma cells coupled with the inhibition of osteoblasts. Hypercalcaemia may be symptomatic with the presence of constipation and fatigue or may be an incidental finding in an asymptomatic patient during a work-up. Ionised calcium may be higher than expected due to concomitant hypoalbuminaemia. Immediate treatment measures include the initiation of intravenous fluids and treatment with corticosteroids, bisphosphonates, and loop diuretics.[50]
Impending bone fracture
Patients with multiple myeloma may present with bone pains secondary to the lytic lesions caused by myeloma cells. Bone x-rays may demonstrate large lesions, involving the long bones with cortical destruction that are often at risk of fracture. These lesions should be treated urgently, typically with internal fixation with or without radiotherapy.
Hyperviscosity syndrome
This is typically seen in the context of an IgM monoclonal protein and Waldenstrom's macroglobulinaemia, although this can also occur with other immunoglobulin types when blood levels are high.[51][52] Measurement of serum viscosity should be undertaken when patients present with suggestive symptoms and signs such as headache, visual symptoms, typical fundoscopic appearances, or mental status changes. Immediate management requires institution of plasmapheresis to enable rapid removal of the paraprotein. This should be accompanied by supportive care measures, including hydration.
Compressive myelopathy
Involvement of the vertebral bodies by the myeloma lesions can result in compression fractures leading rarely to retropulsion of the fractured material posteriorly into the spinal canal with resultant cord compression. Plasmacytomas in the paraspinal region with extension into the spinal canal can also lead to similar symptoms. Development of myelopathy symptoms and signs in a patient with suspected myeloma should raise suspicion and appropriate imaging tests should be ordered, including an MRI. Immediate measures may involve radiotherapy, corticosteroid therapy, or surgical intervention.
Bleeding
Life-threatening bleeding is an uncommon presentation in this group of disorders. Increased bleeding can be related to thrombocytopenia due to the replacement of normal marrow elements by myeloma cells. Normal coagulation can be compromised by non-specific inhibition by the monoclonal protein or due to specific inhibitors of coagulation factors. Acquired von Willebrand's disease and acquired factor VIII abnormalities have been described in the context of monoclonal proteins.[53] Patients with systemic amyloidosis can present with factor X deficiency, thought to be related to binding of the factor by amyloid fibrils.[54]
Venous thromboembolism
The reported incidence of deep vein thrombosis in myeloma ranges from 4% to 20% depending on the nature of therapy and other predisposing factors such as factor V Leiden mutation.[55] Prompt recognition and initiation of anticoagulation therapy is needed.
Infections
Symptomatic monoclonal gammopathies, especially myeloma, are associated with suppression of normal immunoglobulin levels, increasing the risk for infections. The risk is higher with encapsulated bacteria such as pneumococcus. Prompt diagnosis and initiation of appropriate antibiotic therapy are essential to avoid complications. One placebo-controlled phase 3 trial found that levofloxacin prophylaxis significantly reduced febrile episodes and deaths during the initial months after diagnosis of multiple myeloma.[56]
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