The Role Primary Care Plays in Improving Outcomes for Patients with Multiple Myeloma

Primary care physicians serve as the frontline in identifying multiple myeloma patients and shaping their subsequent medical journey. Because the symptoms of multiple myeloma, such as back pain, bone pain and fatigue, can be nonspecific and overlap with other conditions, it can be easy to overlook or misinterpret during office visits with the patient¹. However, by maintaining a heightened awareness and suspicion for multiple myeloma, you can ensure timely referrals for further evaluation and specialist consultations. A proactive approach in primary care can significantly improve patient outcomes, as a prolonged time to diagnosis is associated with more complications and worse patient outcomes². Recognizing that multiple myeloma can disguise itself with common symptoms allows you to guide patients toward an appropriate care pathway and enhance their quality of life.

Delays Lead to Clinical Complications

On average, three visits to Primary Care occur before a multiple myeloma patient is referred to a hematologist, often resulting in a delayed diagnosis³. The likelihood of debilitating complications such as bone disease, anemia, renal impairment, neurological disease, and infections can significantly increase with a delay in diagnosis. In a study, 100% of patients developed complications when their diagnosis was longer than six months from when symptoms were presented.² Further, a diagnostic delay of greater than six months increased the incidence of renal impairment and bone disease in those patients by 2.6 and 2.5 times, respectively, compared to patients diagnosed within 3 months.² This diagnostic interval and time from disease onset to therapeutic intervention can impact disease-free survival, meaning lower quality of life and higher economic impact for the patient and the health system. Inversely, early diagnosis and initiation of treatment are associated with better outcomes².

Multiple Myeloma and its Relation to Monoclonal Gammopathies

Multiple myeloma is a hematologic cancer that is characterized by the clonal proliferation of malignant plasma cells in the bone marrow⁴. It typically evolves from the emergence and unchecked expansion of clonal premalignant plasma cells. This pre-malignancy, known as monoclonal gammopathy of undetermined significance (MGUS), can progress to multiple myeloma as the cell population undergoes further transformation events⁴. These pre-malignant and malignant plasma cells typically retain their capability to produce antibodies, a useful biomarker for their presence in the body. The invasion of the plasma cells into adjacent bone, alongside the overproduction of antibodies (M-proteins) can lead to various complications such as bone disease, anemia, renal dysfunction, and a compromised immune system.⁴

Who is at High Risk of Multiple Myeloma?

Because the symptoms of multiple myeloma are nonspecific and have significant overlap with more common conditions, primary care providers should be aware of high-risk groups for whom they should have heightened awareness of myeloma signs and symptoms. Those demographics that have enhanced risk for multiple myeloma include:

• Increasing age: Myeloma is most frequently diagnosed among people aged 65-74.⁵
• Male sex: Men are more likely to develop the disease than women.⁵
• Race: Myeloma incidence is > 2-fold higher in African American/Blacks than Whites.⁵
• Family history of multiple myeloma: Having a first-degree relative with multiple myeloma or any lympho-hematopoietic cancer, such as non-Hodgkin lymphoma, leukemia, or Hodgkin lymphoma, translates to an increased risk.⁶
• Personal history of a monoclonal gammopathy of undetermined significance (MGUS): Previous diagnoses of premalignant MGUS increase a patient’s risk of progressing to multiple myeloma.¹

What is the Diagnostic Work-up of Multiple Myeloma?

Previously, a diagnosis of active, symptomatic multiple myeloma required the presence of clonal bone marrow plasma cells at >10% and any one or more of the common attributes associated with the disease: hypercalcemia, renal failure, anemia, or bone disease (CRAB). To facilitate diagnosis at an earlier stage, and thus enhance the efficacy of therapeutic intervention, the definition has been modified to include as a myeloma-defining events three biomarkers of malignancy: ≥60% bone marrow plasma cell, >1 focal lesion detected through MRI, and validated biomarkers associated with the monoclonal protein, i.e., an involved/uninvolved serum free light chain ratio ≥100, provided that the involved FLC is ≥100 mg/L.⁷

Proper diagnostic work-up of multiple myeloma, when multiple suggestive signs and symptoms are present, should involve a comprehensive panel of tests. In addition to clinical symptoms, routine bloodwork can also support a s suspicion of multiple myeloma. A complete blood count (CBC) and quantification of lactate dehydrogenase, electrolytes, total protein, albumin, and creatinine are important general tests to assess blood and renal function as well as to determine abnormalities in blood protein content. If initial tests are suggestive of potential myeloma, serum protein electrophoresis (SPE), serum free light chain testing (sFLC), and immunofixation (IFE) are appropriate next steps that can help optimize referrals to hematology.¹ In some cases, imaging for lytic lesions may also be appropriate.

Recommendations for Diagnostic Testing

Historically, serum protein electrophoresis (SPE) alone has been used to detect and measure monoclonal gammopathies. Guidelines now recommend combining serum free light chains (sFLC) with SPE and serum immunofixation (sIFE) to achieve the highest diagnostic sensitivity for these conditions. Together, these assays detect > 99% of cases of multiple myeloma and > 94% of all monoclonal gammopathies, setting your patients on the most reliable path to diagnosis and treatment⁸.

By recognizing the early symptoms and employing the correct diagnostic tests, you have the power to set the trajectory for better patient outcomes.

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