Multiple myeloma diagnosis in primary care

The symptoms of multiple myeloma (MM), such as bone and back pain, recurrent infections and fatigue, are common in primary care, resulting in delays in diagnosis. MM patients (pts) are more likely than other cancer pts to visit three or more times the primary care setting before they are referred to a secondary care specialist.

Constantinos Koshiaris and colleagues from the Nuffield Department of Primary Care, University of Oxford, Oxford, UK, published a study aimed at evaluating the best combination of blood tests to use in primary care for an early consideration or exclusion of a MM diagnosis. Using records from the Clinical Practice Research Datalink (CPRD) from a 2015 MM study, they performed a large case-control analysis to identify blood tests and inflammatory markers that could be associated with MM symptoms. Likelihood ratios (LR) were used to estimate how many times more likely (LR+) a positive test or less likely (LR-) a negative result occurs in individuals with MM compared to an individual without the disease. The results of the study were published in the British Journal of General Practice in August 2018.

Key Data:

• Number of participants = 14,860 (2,703 pts and 12,157 matched controls)
• Matched controls were based on age, sex, and general practice
• Median age = 73 years
• Gender (male) = 53%
• Within the year before diagnosis 55% (8,221/14,860) of participants had at least one blood test
  • Most common blood tests: Creatinine = 50%; full blood count (FBC) = 40%
  • Most common inflammatory markers: Erythrocyte sedimentation rate (ESR); C-reactive protein (CRP); plasma viscosity (PV)
  • Most common test combination: FBC with creatinine and ESR = 13%
• At three years before diagnosis: 84% of pts had at least one blood test vs 66% in controls
• At five years before diagnosis: 85% of pts had at least one blood test vs 70% in controls
• Useful rule-in test = LR+ > 5
• Useful rule-out test = LR- < 0.2
• Rule-in tests for inflammatory markers in the year before diagnosis:
  • Abnormal ESR = 85% of pts vs 46% of controls (odds ratio [OR] = 5.7, 95% confidence interval [CI], 4.1-8.0, P < 0.001; LR+ = 1.9, 95% CI, 1.7-2.0)
  • Abnormal PV = 81% of pts vs 41% of controls (OR = 4.4, 95% CI, 2.2-8.8, P < 0.001; LR+ = 2.0, 95% CI, 1.7-2.3)
  • Abnormal CRP = 46% of pts vs 37% of controls (OR = 1.5, 95% CI, 1.0-2.2, P = 0.05; LR+ = 1.2, 95% CI, 1.1-1.4)
• No blood test could rule out myeloma
• Best inflammatory markers for ruling out disease: ESR (LR- 0.28, 95% CI, 0.24-0.33); PV (LR- 0.32, 95% CI, 0.24-0.44)
• Timing of symptoms:
  • Hemoglobin values started to decrease in both males and females at around three years before diagnosis
  • Anemia was detected in males 24 months before diagnosis and in females 15 months before diagnosis
  • White cell count and platelets: stable and within the normal range at all time points
  • Mean calcium and creatinine values rose rapidly in the last three to six months before diagnosis
  • ESR and PV values started to increase at around two years before diagnosis
  • CRP showed no difference between pts and controls at any time point
  • Back and rib pain, chest infections, chest pain, and nosebleed are more common in pts at around two years before diagnosis
  • Fractures, weight loss, and nausea are more common during the last three to twelve months before diagnosis
  • Strengths of the study: Large sample size representative of the UK population and the primary care environment
  • Limitations of the study: Potential overestimation of diagnostic accuracy measures with the case-control design; missing data; under-reporting or over-reporting of symptoms

Conclusions

This study identifies PV and ESR as better diagnostic markers than CRP for both considering and excluding the possibility of MM for pts examined in the UK primary care setting. In addition, normal values of ESR or PV in combination with normal hemoglobin were identified as exclusion criteria for a diagnosis of MM. FBC components, especially low hemoglobin levels, are among the earliest quantifiable prognostic indicators of the disease.