What are the recommended screening tests and protocols for individuals at high risk of developing multiple myeloma?

Multiple Myeloma Screening

Population-based screening for multiple myeloma is not recommended outside of research protocols. 1

General Population Screening

The European Myeloma Network explicitly states that screening of the general population is not recommended outside of studies. 1 This recommendation is based on:

• The low absolute risk of detecting multiple myeloma in asymptomatic individuals 1
• The absence of proven intervention strategies that improve survival or quality of life when disease is detected early 1
• The lack of evidence demonstrating meaningful impact on mortality or morbidity from early detection 1

High-Risk Individuals: First-Degree Relatives

For individuals with first-degree relatives who have multiple myeloma, routine screening is not recommended outside of research protocols. 1

While first-degree relatives of multiple myeloma patients have a 2-4 times higher relative risk of developing the disease compared to the general population 2, the European Myeloma Network recommends screening only as part of a research protocol due to:

• The still-low absolute risk despite elevated relative risk 1
• The absence of currently available intervention strategies 1
• Unknown benefit of early detection in this population 1

Research Setting Considerations

In a research setting only, screening could potentially be offered to individuals with: 2

• More than one first-degree affected relative, OR
• One first-degree and at least one second-degree relative with multiple myeloma 2

If screening is performed in this research context, the proposed protocol includes: 2

• Annual protein electrophoresis of blood and urine 2
• Starting at age 40 years (or earlier if a family member presented with multiple myeloma at a younger age) 2

Monitoring of Precursor Conditions

The focus should be on appropriate surveillance of diagnosed precursor conditions (MGUS and smoldering myeloma) rather than screening asymptomatic individuals. 1

MGUS Follow-Up

For patients with diagnosed MGUS, follow-up should include: 1

• Careful history and physical examination focusing on symptoms suggesting progression to multiple myeloma, Waldenström macroglobulinemia, AL amyloidosis, or M-protein related disorders 1
• Quantification of M-protein 1
• Complete blood count 1
• Creatinine and calcium levels 1
• If abnormal free light-chain ratio with elevation of involved light chain: NT-pro-BNP and urinary albumin monitoring 1

Smoldering Myeloma Surveillance

For smoldering myeloma, observation at 3-6 month intervals is the category 1 recommendation. 1

The NCCN guidelines stratify patients using the Mayo 2018 20/2/20 criteria (bone marrow plasma cells >20%, M-protein >2 g/dL, FLC ratio >20): 1

• Low-risk patients (0 factors): Observe at 3-6 month intervals (category 1) or enroll in clinical trial 1
• High-risk patients (≥2 factors): Enroll in clinical trial (preferred) or single-agent lenalidomide in carefully selected patients (category 2B) or observation at 3-month intervals 1

Surveillance testing includes: 1

• CBC with differential and platelet count 1
• Serum chemistry (creatinine, albumin, corrected calcium) 1
• Serum quantitative immunoglobulins, SPEP, and SIFE 1
• Serum FLC assay as clinically indicated 1
• 24-hour urine for total protein, UPEP, and UIFE 1
• Imaging (MRI, whole-body low-dose CT, and/or PET/CT) annually or as clinically indicated 1

Key Pitfalls to Avoid

• Do not perform population-based screening outside of research protocols, as there is no evidence of benefit 1
• Do not assume that early detection in high-risk relatives improves outcomes without proven interventions 1
• Patients with evolving MGUS developing M-protein ≥30 g/L should be reclassified as smoldering myeloma and followed every 3-4 months 1
• Rising markers or high-risk factors in smoldering myeloma require close monitoring at 3-month intervals 1