Earlier recognition of multiple myeloma in primary care requires ‘connecting the dots’

March has been designated “Myeloma Action Month” by the International Myeloma Foundation to encourage health care professionals, patient advocates and caregivers to “take action to empower patients and arm them with knowledge.” Healio Family Medicine spoke with oncologists and primary care physicians about awareness of the malignancy in primary care and strategies for diagnosing the disease earlier.

Multiple myeloma is considered relatively rare in the United States, accounting for 1.8% of all anticipated new cancer cases in 2016, with an estimated 30,330 new cases and 12,650 deaths.

The prognosis for multiple myeloma has improved in recent years, due in large part to new therapeutic agents and the use of autologous hematopoietic stem cell transplant. Median survival rates vary by stage, but range from 62 months for patients with stage 1 disease to 29 months for patients with stage 3 disease.

Identifying patients with multiple myeloma can begin in the primary care setting, but the non-specific symptoms make diagnosis challenging and require greater recognition of symptom patterns and patients at increased risk.

The initial symptoms of multiple myeloma include pain, particularly of the back and bones, and fatigue, common complaints in primary care, according to Robert A. Vescio, MD, medical director of the multiple myeloma and amyloidosis program at Cedars-Sinai Medical Center in Los Angeles.

“Back pain and bone pain are the most common early symptoms that people present with,” Vescio said. “If the bone is weakened from a plasmacytoma, a tumor of malignant plasma cells, that can cause a compression fracture. People have back pain for many other reasons, so there is often a lag between symptom onset and diagnosis. In older patients, it may be assumed that they have compression fractures from osteoporosis.”

Healio Family Medicine spoke with Vescio and other clinicians about the initial symptoms of multiple myeloma and the steps that can be taken to increase earlier diagnosis in the primary care setting.

Importance of patient characteristics, related symptoms

In addition to pain and fatigue, early symptoms of multiple myeloma include anemia and renal insufficiency, which may not be recognized immediately as an indicator of multiple myeloma, according to Vescio.

“If the creatinine is rising in a patient who has a history of diabetes or hypertension, or there is another reason to explain why the kidneys are not functioning, a complete workup isn’t always done,” he said.

However, it is this constellation of symptoms — rather than a single issue alone — that can serve as a starting point to expedite the diagnosis of multiple myeloma in primary care.

“If you consider symptoms like bone pain and rising creatinine as separate issues, it’s really hard to diagnose multiple myeloma,” Hae Sung Lee, MD, an attending physician at NYC Health and Hospitals/Metropolitan and clinical assistant professor at New York Medical College, said in an interview. “I think the most important thing in diagnosing multiple myeloma is connecting the dots.”

Patient characteristics can also provide information that may lead to earlier diagnosis. Research is beginning to demonstrate a genetic predisposition to multiple myeloma and other plasma cell dyscrasias; in particular, the paratarg-7 protein may be important. In patients with the array of symptoms that are common in early-stage disease, a family history of multiple myeloma can serve as the impetus to think beyond the traditional causes of back pain or anemia.

“Even though this is not a familial disease, we do know there is a relationship,” according to Saad Usmani, MD, FACP, director of plasma cell disorders and of clinical research in the department of hematologic malignancies at the Levine Cancer Institute at Carolinas HealthCare System. “There are families where, if a first-degree relative has multiple myeloma, there is a slightly increased chance of another family member developing multiple myeloma. We’re not sure whether this is genetically driven or because of environmental exposure those individuals may have had while living under the same roof or in the same geographic area.”

A family history of cancer, including solid tumors and hematologic malignancies, has been associated with an increased risk for multiple myeloma. Men with a family history of cancer and having a first-degree relative with multiple myeloma may also increase an individual’s likelihood of the disease. Black race, however, appears to be the most significant patient characteristic that heightens an individual’s risk.

“Multiple myeloma occurs two and a half times more commonly in blacks compared with whites,” Usmani said. “There is a definite racial disparity when it comes to the incidence and prevalence of this disease.”

Most patients with multiple myeloma are diagnosed at age 65 and older. However, black patients “tend to present at an even earlier age,” according to Usmani, making it “extremely important” for clinicians to be aware that black patients may develop a plasma cell problem.

Diagnostic tests, associated conditions

There are several tests can be utilized in primary care to determine whether issues like back pain and anemia are related to multiple myeloma and not a more general problem.

“If patients have back pain that is persistent, it is reasonable to send the patient for an MRI,” Vescio said. “Sometimes, the bone pain can be in the arm, and an X-ray of the arm will usually make the diagnosis of multiple myeloma.”

A complete blood count and a comprehensive chemistry panel can be used to identify issues with renal function and the blood, according to Usmani.

“The blood count will show if the patient has any degree of anemia,” he said. “In the chemistry panel, you can look at the total protein levels. Myeloma is a disease where a single family of plasma cells are making the same kinds of immunoglobulin proteins. This can result in serum total protein level elevations.”

In plasma cell disorders, surplus production of a clonal component known as the involved light chain can lead to an atypical free light chain ratio. This irregular ratio can be predictive of multiple myeloma and is detectable with a free light chain assay. The free light chain assay is particularly effective for diagnosing rarer cases of multiple myeloma that secrete very little immunoglobulin; amyloid light chain (AL) amyloidosis, a related condition; and monoclonal gammopathy of undetermined significance, or MGUS, which is a precursor to multiple myeloma. Approximately 3% to 4% of patients aged older 50 years develop MGUS; the rate of progression from MGUS to multiple myeloma is 0.5% to 1% per year.

“MGUS can be tricky for primary care physicians,” Vescio said. “As many as 5% of elderly patients with MGUS have bone pain, so tests are done, but they may just have MGUS and another reason for bone pain. I think that’s why some patients aren’t diagnosed right away.”

In addition, the symptoms of multiple myeloma may also indicate other, more immediate concerns that primary care providers are tasked with identifying. This could “absolutely be an issue” that contributes to delayed diagnosis, Lee told Healio Family Medicine.

“Multiple myeloma is not a benign disease. It is a malignant problem,” she said. “But primary care doctors want to make sure that they aren’t missing things like a gastrointestinal malignancy or a vitamin deficiency, which might cause anemia. Primary care physicians usually investigate those problems first.”

Enhancing recognition in primary care

Seminars and educational sessions may be one way to increase understanding of the early symptoms of multiple myeloma among primary care providers and the diagnostic tests available for use in that setting, according to Lee.

In the clinic, further exploration of persistent problems may be an effective strategy, Vescio said.

“I don’t think you can ever blame a primary care provider for not recognizing things the first or second time,” he said. “But if there is a problem that is persistent, it requires further evaluation.”

In addition, increased attention to family history and individual patient characteristics may also expedite diagnosis.

“I think the key is recognizing the patient groups where some of the signs and symptoms may not just be due to regular fatigue or musculoskeletal pain,” Usmani said. “For patients in their 60s or 70s who are developing some of these symptoms, you want to be a little more vigilant — while you’re thinking about other etiologies that can occur in that age group, you should also think about things like multiple myeloma and other hematologic malignancies.”

That said, he believes awareness has increased in recent years.

“In general, I think knowledge of plasma cell disorders and myeloma has improved significantly in the last decade,” Usmani said. “Primary care providers are trying to be cognizant of the fact that these disorders exist. The proportion of patients who are presenting with a higher disease burden, or more advanced disease, does not appear as high as it used to be. There is more interest in the disease due to advances in understanding disease biology and we now have better drugs to treat our patients. We’re starting to see a significant change in survival outcomes. All that adds to improved awareness.” – by Julia Ernst, MS

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Disclosures: Lee, Vescio and Usmani report no relevant financial disclosures.