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These are activities that expand general practice knowledge, skills and attitudes, related to your scope of practice.
These are activities that require reflection on feedback about your work.
These are activities that use your work data to ensure quality results.
Treatment advances mean multiple myeloma survival is improving, and good outcomes largely depend on timely intervention. Non-specific symptoms often start long before diagnosis and may not always raise suspicion, but early identification can help prevent fractures, renal failure and irreversible disability—and increase life expectancy. An expert discusses early myeloma warning signs, appropriate investigations, and when to refer patients to a haematologist.
Myeloma itself is a rare presentation in general practice, but its precursors are more common than you might think, says Dr Nicholas Weber, clinical haematologist at the Royal Brisbane and Women’s Hospital and chair of the education pillar of the Medical and Scientific Advisory Group for Myeloma Australia.
“The prevalence of plasma cell dyscrasias like MGUS [monoclonal gammopathy of undetermined significance] and smouldering myeloma is up to 5% of the population over the age of 40,” he says, citing findings from a major Icelandic screening study.
In Australia, around 2,500 new myeloma cases are diagnosed each year, and approximately 20,000 people live with it. Incidence rises with age, which can make it harder to identify, he notes.
“Most of our diagnoses are being made in people in their 60s and 70s. In that age group, other comorbidities are often a competing factor and can contribute to delays in diagnosis or misdiagnosis.”
Therapeutic advances have led to improved life expectancy outcomes, he adds.
“We’re seeing that the average survival from diagnosis for all age groups taken together is around six to seven years, which is much longer than what we were seeing back in the 1990s and early 2000s.”
Myeloma arises from plasma cells that undergo malignant transformation and proliferate clonally within the bone marrow, Dr Weber explains. The abnormal cells produce excessive amounts of a single immunoglobulin comprised of two heavy chains (usually IgG or IgA), and two light chains (either kappa or lambda).
The intact immunoglobulin is referred to as a monoclonal (M) protein, or paraprotein. In some cases, the malignant cells do not produce heavy chains but continue to secrete free light chains into the plasma.
The common clinical manifestations of myeloma are described by the CRAB criteria: Calcium elevation, Renal insufficiency, Anaemia, and destructive Bone lesions, he says.
Plasma cell mutations are actually present many years before myeloma develops during a phase known as monoclonal gammopathy of undetermined significance (MGUS)—when monoclonal proteins are found in the blood of patients with no CRAB features, he explains.
“And we know that all patients with myeloma had MGUS, but only a small proportion of patients with MGUS proceed to myeloma.”
Smouldering myeloma is an intermediate phase during which patients have more abnormal plasma cells in their bone marrow or a higher protein concentration in their blood (> 30 grams per litre) than those with MGUS but still lack clear clinical features of myeloma.
“We watch these patients a bit more closely because their disease burden is increasing, their rate of progression to myeloma is higher than patients with MGUS, and there’s a lot of focus on identifying high-risk smouldering myeloma patients and potentially treating them before they develop myeloma.”
High risk is defined by M protein >20g/L plus a free light chain ratio >20 plus bone marrow plasma cells >20%, he explains. “This group have a 44% risk of progression to myeloma within two years of diagnosis.”
Early symptoms are typically non-specific, Dr Weber notes. “Oftentimes when we look back, we can see signs of myeloma months to years before the diagnosis is made. And it’s not because these signs are being missed. You don’t have a smoking gun that helps make the diagnosis in the early stages.”
Fatigue is common and especially concerning if it’s associated with weight loss, profound lethargy, and inability to manage usual activities. “And that’s often reflected in the blood test as anaemia as well,” Dr Weber says.
Bone pain with red flag features should also raise suspicion, he says. “It’s persistent pain that’s not responding to usual measures like rest, heat packs and analgesia. It can worsen at nighttime or wake people from sleep, and it’s not clearly related to any mechanical cause.”
In some patients, the first symptom is a fracture following minimal trauma, such as a sneeze or minor injury. Recurrent infections are associated with myeloma but rarely occur at the start, he adds.
In many cases, myeloma is first suspected when blood tests ordered for other reasons (such as routine screening or health monitoring) return abnormal results.
Given myeloma and its precursors are frequently discovered incidentally, it’s important to look for flags in the biochemical panel, Dr Weber says.
He notes patients often have raised protein readings—especially the globulin fraction. “Raised globulins, low albumin is a sign that something’s being overproduced. And that can be a marker of a plasma cell dyscrasia.”
Other suspicious abnormalities include:
“If we suspect myeloma, we need to establish that there’s evidence of a monoclonal process,” Dr Weber explains. “So that’s with serum protein studies and free light chains. At the same time we need to look for any evidence of myeloma-related organ damage—going back to the CRAB features.”
While GPs are not expected to diagnose myeloma, they can do much of the workup, he says. He recommends running the following tests:
“If serum electrophoresis, free light chain ratio, and urine Bence Jones protein are all completely normal, then we can very confidently rule out myeloma. If any of them are abnormal, we need to be looking at referral,” he says.
“If we identify myeloma early in GP, we can really make a difference in averting disaster, dialysis dependency, pathological fractures, etcetera.”
Plain x-rays are a reasonable first choice for identifying fractures or gross lytic changes in patients complaining of pain, Dr Weber says.
“But I wouldn’t be reassured by a normal x-ray if the patient’s symptoms are persistent. And if they’ve got evidence of a monoclonal protein or abnormal free light chains, it would be reasonable to do a low-dose CT skeletal survey as an initial investigation, looking for lytic bone disease, and enclosing that with the referral to help us with triage.”
This decision has traditionally hinged on symptoms and clinical findings, Dr Weber explains.
“In most cases, if the monoclonal protein is low (less than 15g/L) and the light chain ratio is normal or mildly out of range, then if patients are completely well with normal imaging and normal blood work, we’ll defer the bone marrow biopsy, consider the patient to have MGUS and monitor them accordingly.”
Patients with higher risk features or organ involvement will proceed to biopsy, he adds, noting a tool developed in the Icelandic study is increasingly used to make evidence-based biopsy choices.
Patients with suspected spinal cord compression, uncontrolled pain, severe anaemia requiring transfusion, severe or rapidly progressing renal impairment, or severe hypercalcemia (over 3.5 millimoles per litre) should be seen urgently in an emergency department, Dr Weber says.
Patients with a monoclonal protein or an abnormal light chain ratio and any signs suspicious of myeloma-related organ damage (CRAB features) should be referred for urgent outpatient assessment. “We usually try and see those patients within two weeks in our public system,” he says.
Asymptomatic patients with a paraprotein or an abnormal light chain ratio but otherwise normal investigations can be referred non-urgently. “And we would generally try and see them within three months.”
Follow up protocols vary depending on progression risk, Dr Weber says. Specialists often follow up patients deemed to be low risk annually with blood work. Those at intermediate or high risk are usually seen four-to-six-monthly for the first two years. “Then depending on the tempo of progression, we may continue to follow them up through the hospital clinic or discharge them back to the community.”
If patients are discharged back to their GP, the specialist will recommend intervals for testing and criteria for re-referral.
While myeloma is not curable, many patients are living longer with it (about 7 years on average), often on continuous treatment—which can lead to other challenges, he notes.
“One of the biggest issues we face in this population is infection, so we often rely on GPs to ensure patients are up to date with their vaccination schedule.”
They also have higher rates of other malignancies, particularly skin cancer and secondary haematological cancers, and can get the usual age-related cancers.
“So skin checks and keeping up to date with age-appropriate cancer screening—faecal occult blood testing, mammography, pap smears, etc—that’s all really important as well.”
If you have any questions about test results or when to refer, he recommends calling your local hematology service. “We’re usually very approachable and care very much about getting patients seen in the right timeframe.”
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