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Multiple myeloma referral and follow-up for healthcare providers

  • When to refer to a specialist
  • Patient handoff and communication
  • Evaluation of patients with MGUS
  • Ongoing role of a PCP in myeloma care

Introduction

Primary care's role in the referral of multiple myeloma

Primary care providers (PCPs) have an essential role in the detection of multiple myeloma and referral for prompt diagnosis and care.1 Patients often present first to primary care providers, but testing and referral is also often delayed, resulting in repeat visits and a median diagnostic lag time of about 7 months after patients first present with bone pain.1

 

The non-specific symptomatology of myeloma can make it challenging to suspect it early on in a PCP’s differential diagnosis.1,2 Physicians often try to rule out more common causes of symptoms such as back pain and fatigue, treat them as transient irritations, or attribute them to aging or other conditions.2

Early detection of multiple myeloma can reduce complications, improve survival, and enhance quality of life.1,3 Proactive testing of patients with back pain and other symptoms or unexplained laboratory abnormalities with monoclonal protein testing (serum protein electrophoresis (SPEP), serum free light chain testing (sFLC), and serum immunofixation(sIFE)), can help identify multiple patients early, ensuring timely referrals.

When to refer to a specialist

Immediate referral to a hematology/oncology specialist is merited when a patient has an elevated SPEP and/or abnormal sFLC ratio, accompanied by any of the CRAB (hypercalcemia, renal insufficiency, anemia, lytic bone lesions [or bone pain in the absence of imaging]) features.4,5

Urgent referral to a specialist may also be merited for high concentrations of monoclonal protein (M protein) detected via SPEP, a significantly abnormal sFLC ratio, or in the case of identified IgD or IgE paraprotein—even in the absence of CRAB symptoms.4

PCPs may also wish to consult a hematology/oncology specialist for guidance on referrals or follow-up testing when sFLC assay reveals an abnormal kappa/lambda ratio, or the SPEP or immunofixation (IFE) reveal M protein, even if at low concentrations.2 A consultation with a hematology/oncology specialist can aid in identifying the best next steps for a patient in the instance of abnormal results.2

Patient handoff and communication

When referring to hematology/oncology specialists, provide context surrounding patient signs and symptoms in addition to test results to inform the urgency of the referral.2

Before diagnosis: Talking with your patient about abnormal results

Diagnostic uncertainty from abnormal test results can result in considerable distress and anxiety as patients await a final diagnosis.6 It may be helpful for PCPs to provide information and support to their patients as they wait for answers, although this is not a substitute for specialist consultation.6 PCPs can offer context to patients about the degree of abnormality of their test results as well as the significance of other signs and symptoms to help them understand their risk of malignant disease or the urgency of their referral.

  • Final diagnosis will determine a patient’s prognosis and care plan. Some diagnoses do not require treatment or follow-up testing, while others may require urgent intervention.2,4
  • Patients with classic symptoms of myeloma or significant laboratory abnormalities should expect bone imaging and/or bone marrow biopsy as well as additional lab testing when they meet with a specialist.2
  • Not all patients with abnormal results on SPEP/IFE or sFLC testing will be diagnosed with multiple myeloma. Premalignant conditions, such as monoclonal gammopathy of undetermined significance (MGUS), can also be identified with SPEP and IFE, and evaluated with sFLC.7,8
  • MGUS is more common than malignant disorders. For example, in a study at the Mayo Clinic of 1,684 patients diagnosed with monoclonal gammopathy, 921 cases (55%) were MGUS.8 MGUS is fairly common in the US, affecting about 3.2% of White people aged 50+ and 2-3 times that many Black people/African Americans.9
  • While not all patients with MGUS will progress to multiple myeloma, all myeloma cases develop from MGUS.4,5,9,10 It is a precursor for several lymphoplasmacytic malignancies.4,10
  • Patients with MGUS are typically evaluated with laboratory tests at predetermined intervals, unless they begin to experience new or worsening clinical symptoms prompting earlier evaluation.4,10
  • Patients diagnosed with premalignant conditions who are followed up have improved outcomes if they do progress to myeloma, compared to those first diagnosed with active myeloma.11
  • Clinical condition of the individual patient is an important prognostic indicator; those diagnosed with myeloma soon after symptom onset experience fewer complications.3

Evaluation of patients with MGUS

Patients with MGUS have an absence of myeloma-defining events, as well as monoclonal gammopathy <3 g/dL and fewer than 10% bone marrow plasma cells.5,12 Risk of progression to a symptomatic plasma cell dyscrasia requiring therapy depends on MGUS subtype, but overall is considered to be about 1% 
per year.13

Many patients with MGUS will be monitored by PCPs unless test results or symptoms merit referral to a specialist. MGUS monitoring guidelines vary, but many proposed algorithms focus on risk of progression.5,10 After initial diagnosis, most algorithms recommend screening every 3-6 months for the first 6-12 months, after which monitoring may be every 2-3 years (or never, without reason) for stable low-risk cases, or annual for high-risk patients.4,5,10

Tests valuable for evaluating patients with MGUS include sFLC, SPEP, complete blood counts, and creatinine and calcium assessments.10 Careful attention to clinical symptoms is also important to suspicion for MGUS progression.10

Any patients with MGUS who develop clinical or laboratory “red flags” should be evaluated for progression to a plasma cell dyscrasia.10

Red flags in
MGUS
monitoring

In monitoring patients with MGUS, the following problems are considered clinical red flags:10

  • Unintentional weight loss, excessive fatigue, fever, night sweats, or other constitutional signs of malignancy
  • Bone pain or pathologic fractures
  • Neuropathy
  • Lymphadenopathy
  • Organomegaly
  • Neuropathy
  • Mucocutaneous bleeding

    •  

Laboratory test-based red flags for MGUS progression include:10

  • Anemia
  • Hypercalcemia
  • Elevated creatinine or renal impairment
  • Increasing M protein concentration in blood or urine
  • Increasing concentration of the involved sFLC light chain, either kappa or lambda
PCPs have a critical role in the early identification of multiple myeloma and related disorders.1,2 Appropriate testing and timely referrals can improve survival and quality of life.1

After myeloma diagnosis: The ongoing role of a PCP in myeloma care

Improvements in treatment have resulted in increasing median survival for individuals with multiple myeloma.14 Patients may live for years or even decades after a new diagnosis, meaning PCPs may have long-term involvement in ongoing care for patients with multiple myeloma.14

Although myeloma-specific treatment and related side effects are handled by the prescribing specialist, close relationships between myeloma patients and their PCPs can support well-rounded care and improved quality of life.14

PCPs can support their patients with multiple myeloma through:14

  • Offering supportive treatment or side effect management in consultation with the patient’s hematologist/oncologist
  • Helping patients address new symptoms that may arise
  • Identification of emergent problems related to myeloma, such as vertebral compression fractures
  • Optimizing care for pre-existing comorbidities
  • Preventing or addressing age- and lifestyle-related comorbidities
  • Vaccinations and infection prevention
  • Early detection and collaborative treatment of acute infections
  • Surveillance for secondary malignancies
  • Survivorship support and care coordination

Collaborating with your patient’s specialist can help inform appropriate management and monitoring strategies for myeloma-related problems or other health needs.14

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References
  1. Seesaghur A, et al. Clinical features and diagnosis of multiple myeloma: a population-based cohort study in primary care. BMJ Open 2021;11:e052759 
  2. Mikhael J, Bhutani M, Cole CE. Multiple Myeloma for the Primary Care Provider: A Practical Review to Promote Earlier Diagnosis Among Diverse Populations. Am J Med 2023;136(1):33-41
  3. Kariyawasan CC, et al. Multiple myeloma: causes and consequences of delay in diagnosis. QJM 2007 Oct;100(10):635-40 
  4. Drayson M, et al; for Myeloma UK working group for laboratory best practice. Laboratory practice is central to earlier myeloma diagnosis: Utilizing a primary care diagnostic tool and laboratory guidelines integrated into haematology services. Br J Haematol 2024 Feb;204(2):476-486 
  5. Rajkumar SV, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 2014; 15:e538-e548 
  6. McQueen A. Waiting for a cancer diagnosis. Cancer Nursing Practice 2009;8(4):16+ 
  7. Katzmann JA, et al. Screening panels for detection of monoclonal gammopathies. Clin Chem 2009 Aug;55(8):1517-22 
  8. Kyle RA, Rajkumar SV. Epidemiology of the plasma-cell disorders. Best Pract Res Clin Haematol 2007 Dec;20(4):637-64 
  9. Wadhera RK, Rajkumar SV. Prevalence of monoclonal gammopathy of undetermined significance: a systematic review. Mayo Clin Proc 2010 Oct;85(10):933-42 
  10. Abeykoon JP, Tawfiq RK, Kumar S, Ansell SM. Monoclonal gammopathy of undetermined significance: evaluation, risk assessment, management, and beyond. Fac Rev 2022 Nov 29;11:34 
  11. Sigurdardottir E, et al. The role of diagnosis and clinical follow-up of monoclonal gammopathy of undetermined significance on survival in multiple myeloma. JAMA Oncology 2015; 1:168-174 
  12. Kumar SK, et al. Multiple Myeloma, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2023 Dec;21(12):1281-1301 
  13. Kyle RA, et al. Long-term follow-up of monoclonal gammopathy of undetermined significance. N Engl J Med 2018; 378:241-249 
  14. Monteith BE, Sandhu I, Lee AS. Management of Multiple Myeloma: A Review for General Practitioners in Oncology. Curr Oncol 2023 Apr 22;30(5):4382-4401