GPs can speed up multiple myeloma diagnosis

Back pain, fatigue, weight loss and abnormal blood tests are red flags that warrant investigation, a UK study finds.

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Bone and back pain are early, but often overlooked, red flags for multiple myeloma, according to a large study of UK general practice. 

The study of more than 2600 adults with newly diagnosed multiple myeloma found that half had bone pain in the two years prior to their diagnosis, with back pain the most common type. 

“Patients with myeloma have one of the longest time-to-diagnosis intervals among cancers, with an average time between symptom onset and multiple myeloma diagnosis of 99 days,” the authors said. 

“Compared with patients with other cancers, they also have the most repeated consultations occurring in primary care before referral to a specialist, with 50% experiencing three or more repeat consultations.”

This audit of 17 million primary care records found that symptomatic bone pain was recorded seven months on average before a diagnosis was made. 

The researchers also found that investigations of the CRAB criteria, which included hypercalcaemia, renal impairment, anaemia and bone lesions, were underused. 

Early diagnosis was crucial to survival and limiting sometimes irreversible end organ damage due to more advanced disease, said myeloma expert Dr Anna Kalff, consultant haematologist at the Alfred Hospital in Melbourne.

“The longer the diagnosis is delayed, the more advanced the disease may become, which may lead to a worse prognosis. It may be more difficult for patients to tolerate treatment,” she said. “So it’s really important to try to diagnose it early.” 

The population-based cohort study found that regardless of bone pain levels before diagnosis, only one in three patients were tested for hypercalcaemia, two in three for anaemia and three in four for renal function. 

Of all the patients who were eventually diagnosed with multiple myeloma, only one in five were investigated for all four criteria. 

Imaging was also requested in two out of three patients who reported bone pain or skeletal-related events and one in three patients without the pain.

“Diagnostic tests to explore evidence of the CRAB criteria were underused,” said the researchers, who found that patients were typically diagnosed one to two months after an abnormal laboratory result.

“Our findings suggest that GPs could have significant input in improving the time to diagnosis of multiple myeloma,” they added. 

“Back pain combined with other symptoms such as fatigue and weight loss, or back pain combined with abnormal blood tests warrant definitive investigation for multiple myeloma.”

Dr Kalff said that the UK findings were similar to the situation in Australia. 
“Something that we do notice is that patients often have had symptoms for a long time before the penny drops, and they end up with more advanced disease.”

This research highlighted that people could present with very nonspecific symptoms, so it was important for clinicians to keep this as a potential differential diagnosis in the back of their mind, she said. 

In particular, it was worth investigating red flag symptoms such as bony pain that was persisting and getting worse, multifocal or unexplained osteoporosis, or unexplained fractures. 

“Back pain is a red flag symptom because patients can present with back pain and then develop spinal cord compression,” she said. “And then if they’re not treated quickly enough, damage can be irreversible and patients can have permanent loss of function.”

Younger patients in particular often had pain for longer before it was investigated, Dr Kalff added. 

“They might see a physio, chiropractor or an osteopath and have multiple treatments before an X-ray is done,” she said “Then the X-ray is done and an abnormality is found and they get referred on.” 

Other possible warning signs included increased globulins found in more routine liver function tests, said Dr Kalff, who said paraprotein and free light chain tests should be performed if clinicians were suspicious. 

She urged clinicians to call a haematologist if they had any questions or had a patient with abnormal results on these tests. 

BMJ 2021, online 6 October