Identifying opportunities for earlier diagnosis of myeloma

Problem

Myeloma is a rare haematological cancer of the bone marrow. Patients experience non-specific symptoms like musculoskeletal pain, infection, and nausea. Diagnostic delays are common and it has been shown that patients with a time to diagnosis of more than 6 months have a more advanced stage of the disease and more complications, such as renal disease. It remains unclear for how long symptoms are present before diagnosis. The aim of this study was to identify when myeloma symptoms and investigations start to indicate myeloma and to distinguish early symptoms from late symptoms.

Approach

This is a secondary analysis of CPRD data from a case-control study including 2703 myeloma cases and 12157 controls which identified 11 symptoms and 5 investigations as predictive of myeloma. Percentages of patients who were experiencing each symptom were estimated for both cases and controls for each 3 month interval going back up to 5 years before diagnosis. Conditional logistic regression was used to estimate the odds ratio for each time point. Mean and confidence intervals were estimated for each 3 month interval for laboratory investigations. Multivariate conditional logistic regression models were fitted by excluding the last 3 and 9 months before diagnosis.

Findings

Most symptoms show a similar pattern with the majority of symptoms spiking in the year before diagnosis and especially in the last 3 months. Symptoms like back pain, chest pain, rib pain and chest infections are consistently higher in myeloma patients even 2 years before diagnosis. Haemoglobin was consistently lower in myeloma patients while creatinine and calcium only increased in the last 6 months before diagnosis. Mean C-reactive protein was similar between cases (19.1, 95% CI: 15.6-22.6) and controls (17.0, 95% CI: 12.1-21.9) at 3 months before diagnosis while erythrocyte sedimentation rate was much higher in cases (74.8, 95% CI: 18.6-22.4) compared to controls (20.5, 95% CI: 18.6-22.4). In the multivariate model where the last 9 months were excluded creatinine and calcium were excluded from the model while cytopenia (OR: 2.4, 95% CI: 1.9-2.9), mean corpuscular volume (OR: 1.9, 95% CI: 1.3-2.7) and raised inflammatory markers (OR: 1.7, 95% CI: 1.3-2.1) were retained.

Consequences

Our results suggest that musculoskeletal symptoms like back pain and rib pain and infections can be present in myeloma patients up to 2 years before diagnosis. Nausea manifests in the last 6 months which is around the same time that creatinine and calcium start to rise. Abnormal full blood count and inflammatory markers, especially ESR, appear to be early indicators of the disease.