Changes

September 2025 — reviewed. A literature search was conducted in July 2025 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. No major changes to the recommendations have been made.

Update

Goals

To support primary healthcare professionals to: 

• Make a working diagnosis of multiple myeloma.
• Refer people with suspected multiple myeloma appropriately to secondary care.
• Manage symptoms of multiple myeloma and adverse effects of treatment.
• Communicate effectively with people with end-stage multiple myeloma and their family/carers to plan future and palliative care.

Outcome measures

Audit criteria

QOF indicators

QIPP - Options for local implementation

No QIPP indicators were found during the review of this topic.

NICE quality standards

Haematological cancers

People with haematological cancer have an integrated report produced by a specialist integrated haematological malignancy diagnostic service (SIHMDS) that is shared with the haemato-oncology multidisciplinary team (MDT).

[NICE, 2017]

Definition

• Multiple myeloma is a progressive malignant disease of the plasma cells which produce immunoglobulin — it affects multiple organs and systems, including the bones, kidneys, blood, and immune system.
  • The condition is characterised by a proliferation of abnormal monoclonal immunoglobulins in the blood, referred to as paraproteinaemia.
  • It is typically preceded by a premalignant stage called monoclonal gammopathy of uncertain significance (MGUS) — MGUS progresses to multiple myeloma or related malignancy at a rate of 1% per year.
  • In some people, an intermediate asymptomatic, but more advanced pre-malignant stage, ‘smouldering multiple myeloma’ may be identified. Risk of progression to myeloma from smouldering multiple myeloma is about 10% per year in the first 5 years after diagnosis.
• Diagnosis of multiple myeloma involves detection of:
  • End organ damage (suggested by hypercalcaemia, renal impairment, anaemia, and bone lesions).
  • Specific biomarkers (including clonal bone marrow plasma cells and serum-free light chains).

[NICE, 2018; Bird, 2019; Rajkumar, 2020; Dimopoulos, 2021; Sive, 2021; Cowan, 2022]

Prevalence

• In the UK [Bird, 2019; Rajkumar, 2020; CRUK, 2025]:
  • Around 6240 people are newly diagnosed with myeloma per year. Incidence has increased by around a third since the early 1990s.
  • Multiple myeloma is the second most common haematological malignancy and accounts for at least 2% of all cancer-related deaths (approximately 3100 deaths per year).
  • Around 43% of new cases are diagnosed in people aged 75 years or older.
  • Multiple myeloma is more common in men (58% of cases) than in women (42% of cases) and in Black people than in White or Asian people.
• In Europe [Dimopoulos, 2021]:
  • The incidence of multiple myeloma is 4.5–6.0 per 100,000 people per year.

Risk factors

• Risk factors for multiple myeloma include [Cowan, 2022; CRUK, 2025]:
• Increasing age:
  • In the UK, age-specific incidence rates increase from around 50–54 years and are highest in the 80–84 age group for females and 85–89 age group for males.
  • 43% of new cases diagnosed between 2017 and 2019 were in people aged 75 years or older.
• Sex:
  • Multiple myeloma is more common in men than in women — in the UK, 58% of multiple myeloma cases are in males and 42% are in females.
• Ethnicity:
  • The risk of myeloma is more than twofold higher in Black people, compared to White or Asian people.
• Positive family history:
  • People with a family member with multiple myeloma or monoclonal gammopathy of unknown significance (MGUS) may be at increased risk of developing the disease.
  • A study by the International Multiple Myeloma Consortium that pooled data from 11 case‐control studies (2843 cases, 11,470 controls) identified an increased risk of multiple myeloma in people who had a first‐degree relative with multiple myeloma (OR = 1.90, 95% CI 1.26 to 2.87). This increase was particularly marked among men (OR = 4.13, 95% CI 2.17 to 7.85) and African Americans (OR = 5.52, 95% CI 1.87 to 16.27) [Schinasi, 2016].
• Obesity:
  • Being overweight or obese is thought to be a modifiable risk factor in around 14% of myeloma cases in the UK.
• MGUS:
  • In most people, MGUS does not cause symptoms or require treatment. The risk of progression of MGUS to multiple myeloma or related disorders is about 1% per year.
• Autoimmune conditions
  • Risk of myeloma and MGUS is increased in people with pernicious anaemia.
• Occupational exposures
  • Firefighters appear to have an increased risk of multiple myeloma. Exposure to dioxin and Agent Orange have also been associated.

Prognosis

• Multiple myeloma is usually an incurable disease.
  • Disease course is variable, with survival times ranging from a few weeks to more than 20 years.
• Advances in treatment and supportive care have markedly improved survival.
  • Most people respond to initial treatment and enter a period of disease stability. Subsequent relapses become less responsive to treatment, leading to end-stage disease.
  • Some treated patients survive progression-free for more than 10 years, but around 10% die within 1 year of diagnosis (often as a result of infection, renal failure, or cardiovascular event).
  • In England, of people diagnosed with myeloma between 2017 and 2019 [CRUK, 2025]:
    • 84.5% survived for 1 year or more.
    • 57% survived for 5 years or more.
    • 37.8% are predicted to survive for 10 years or more.
• Survival is related to many factors, including age and stage at diagnosis. In England [CRUK, 2025]:
  • Around three-quarters of men and 83% of women diagnosed with myeloma aged 15–49 years survive their disease for 5 years or more, compared with approximately 20% of people diagnosed aged 75 years and over (data from 2018).
  • Around 97% of people diagnosed at Stage 1 survive their disease for at least 1 year, compared with 79% of patients diagnosed at Stage 3 (data from 2016 to 2020).
• Unfavourable prognostic signs at presentation include beta-2 microglobinemia, renal impairment, high plasma cell counts, diffuse multiple bone lesions or fracture, marked anaemia, and hypercalcaemia.

[Snowden, 2017; NICE, 2018; Mohty, 2019; Guzdar, 2020; Herget, 2020; Sive, 2021; CRUK, 2025; Kumar, 2025]

Complications

• Pathological bone fractures due to osteolysis from proliferation of abnormal plasma cells in the bone marrow — the vertebrae, femur, humerus, and ribs are most often affected.
• Spinal cord compression due to direct compression of the spinal cord by tumour tissue, or to vertebral collapse due to erosion of the vertebrae.
• Renal damage from obstruction of renal tubules by excess light chains.
• Hypercalcaemia due to bone lysis.
• Impaired resistance to infection due to abnormal immunoglobulin production.
  • Recurrent infection with pneumococcal and Haemophilus organisms is common, as is exacerbation of Herpes zoster infection.
• Anaemia due to disordered blood synthesis.
• Haemostatic abnormalities that may lead to bleeding (for example epistaxis) or thrombosis.
• Peripheral neuropathy due to myeloma or treatment.

[Bingham, 2017; Mohty, 2019; Guzdar, 2020; Herget, 2020; Rajkumar, 2020; Sive, 2021; Cowan, 2022; Kumar, 2025]

When should I suspect multiple myeloma?

• Multiple myeloma may present with non-specific symptoms.
• Suspect multiple myeloma in adults, particularly over 60 years of age, with:
  • Unexplained bone pain (often in the lower back or thoracic area).
    • Present in up to 60–70% of people and may have pre-existed for months.
  • Fatigue — present in about 30% of people.
  • Symptoms of hypercalcaemia (such as bone pain, abdominal pain, depression, confusion, muscle weakness, constipation, thirst, and polyuria) — present in up to 30% of people.
    • For more information, see the CKS topic on Hypercalcaemia.
  • Weight loss — present in about 25% of people.
  • Symptoms related to hyperviscosity, such as headache, visual disturbance, cognitive impairment, breathlessness, or mucosal bleeding — present in less than 7% of people.
  • Symptoms of spinal cord compression (such as sensory loss, paraesthesiae, limb weakness, difficulty walking, sphincter disturbance, and spinal deformity) — present in about 5% of people.
  • Fever — present in less than 1% of people.
• Multiple myeloma may present with other complications such as pathological fractures and recurrent infection.
• Examination may be normal. In some people, there may be:
  • Hepatomegaly — present in about 4% of people.
  • Splenomegaly — present in about 1% of people.
  • Lymphadenopathy — present in about 1% of people.
• Occasionally, multiple myeloma can be asymptomatic (or 'smouldering') and is identified from incidental findings on blood tests, such as:
  • Normochromic, normocytic anaemia — present in up to 70% of people.
  • Renal impairment — present in about 50% of people.
  • Hypercalcaemia — present in about 15% of people.
  • Raised erythrocyte sedimentation rate (ESR), plasma viscosity, serum protein, or globulin.

Differential diagnosis

The differential diagnoses of multiple myeloma include:

• Depression
  • Clinical features include fatigue, reduced energy, and weight loss. For more information, see the CKS topic on Depression.
• Osteoarthritis
  • Clinical features include joint stiffness and pain. For more information, see the CKS topic on Osteoarthritis.
• Diabetes mellitus
  • Clinical features include fatigue, weight loss, recurrent infections, and reduced energy. For more information, see the CKS topics on Diabetes - type 1 and Diabetes - type 2.
• Polymyalgia rheumatica
  • Clinical features include a raised erythrocyte sedimentation rate and systemic features such as low-grade fever, fatigue, and weight loss in a person aged over 50 years. For more information, see the CKS topic on Polymyalgia rheumatica.
• Monoclonal gammopathy of unknown significance (MGUS)
  • Clinical features include the presence of serum M protein in an apparently healthy person. This condition is often benign but progresses to multiple myeloma or related disorders at a rate of around 1% each year, with a latent period of up to 20 years.
• Waldenstrom's macroglobulinaemia
  • Clinical features include hyperviscosity syndrome, organomegaly, and lymphadenopathy, presenting in a person with an average age of 65 years.
• Osteosclerotic myeloma (polyneuropathy, organomegaly, endocrine disease, M protein in the blood, and skin lesions [POEMS] syndrome)
  • Clinical features include marked polyneuropathy with widespread neurological involvement, hepatomegaly, splenomegaly, sclerotic bone lesions, endocrine disease, which might manifest as gynaecomastia, M protein in the blood, and skin lesions.
• Amyloid light chain (AL) amyloidosis
  • Clinical features include fatigue, weight loss, hepatomegaly, macroglossia, chronic kidney disease, heart failure, postural hypotension, carpal tunnel syndrome, and peripheral neuropathy.
• Heavy chain disease
  • Clinical features include weakness, fatigue, fever, lymphadenopathy and hepatosplenomegaly, with a portion of the immunoglobulin heavy chain in the serum and/or urine.
• Non-Hodgkin's lymphoma
  • Clinical features include fever, night sweats, weight loss, lymphadenopathy, and splenomegaly. Lymph node biopsy is diagnostic. For more information, see the CKS topic on Haematological cancers - recognition and referral.
• Plasma cell leukaemia
  • Clinical features include bone pain, fatigue, recurrent infection, mucosal bleeding, hypercalcaemia, renal impairment, hepatomegaly, and splenomegaly.

Scenario: Suspected multiple myeloma

From age 18 years onwards.

Scenario: Confirmed multiple myeloma

From age 18 years onwards.

Scenario: End-stage multiple myeloma

From age 18 years onwards.

Analgesia

For prescribing information on paracetamol and codeine, see the CKS topic on Analgesia - mild-to-moderate pain.

Search strategy

Scope of search

A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on primary care management of multiple myeloma.

Search dates

April 2020 - July 2025

Key search terms

The terms listed below are the core search terms that were used for Medline.

• Multiple myeloma/di Diagnosis
• Myeloma$ or “multiple myeloma$ ti,ab.
• Prognosis/ Risk assessment/ Referral and consultation/ Primary Health care/ Prevalence/
• Monoclonal grammopathy.kw.
• Risk stratification.kw.
• Primary care.kw.

Sources of guidelines

• National Institute for Health and Care Excellence (NICE)
• Scottish Intercollegiate Guidelines Network (SIGN)
• Royal College of Physicians
• Royal College of General Practitioners
• Royal College of Nursing
• NICE Evidence
• World Health Organization
• Guidelines International Network
• TRIP database
• Agency for Healthcare Research and Quality
• National Health and Medical Research Council (Australia)
• Royal Australian College of General Practitioners
• British Columbia Medical Association
• Canadian Medical Association
• Alberta Medical Association
• Michigan Quality Improvement Consortium
• Singapore Ministry of Health
• National Resource for Infection Control
• RefHELP NHS Lothian Referral Guidelines
• Medline (with guideline filter)
• Driver and Vehicle Licensing Agency
• NHS Health at Work (occupational health practice)

Sources of systematic reviews and meta-analyses

• The Cochrane Library:
  • Systematic reviews
  • Protocols
  • Database of Abstracts of Reviews of Effects
• Medline (with systematic review filter)
• EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

• NIHR Health Technology Assessment programme
• The Cochrane Library:
  • NHS Economic Evaluations
  • Health Technology Assessments
• Canadian Agency for Drugs and Technologies in Health
• International Network of Agencies for Health Technology Assessment

Sources of randomized controlled trials

• The Cochrane Library:
  • Central Register of Controlled Trials
• Medline (with randomized controlled trial filter)
• EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

• Drug and Therapeutics Bulletin
• TRIP database
• Central Services Agency COMPASS Therapeutic Notes

Sources of national policy

• Department of Health
• Health Management Information Consortium (HMIC)

Patient experiences

• Healthtalk
• BMJ - Patient Journeys

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

• British National Formulary (BNF)
• electronic Medicines Compendium (eMC)
• European Medicines Agency (EMEA)
• Medicines and Healthcare products Regulatory Agency (MHRA)
• REPROTOX
• Scottish Medicines Consortium
• Stockley's Drug Interactions
• TERIS
• TOXBASE
• Micromedex
• UK Medicines Information

Stakeholder engagement

Our policy

The external review process is an essential part of CKS topic development. Consultation with a wide range of stakeholders provides quality assurance of the topic in terms of:

• Clinical accuracy.
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Evidence exclusion criteria

Our policy

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Studies identified during literature searches are reviewed to identify the most appropriate information to author a CKS topic, ensuring any recommendations are based on the best evidence. We use the principles of the GRADE and PICOT approaches to assess the quality of published research. We use the principles of AGREE II to assess the quality of published guidelines.

Standard exclusions for scoping literature:

• Animal studies
• Original research is not written in English

Possible exclusions for reviewed literature:

• Sample size too small or study underpowered
• Bias evident or promotional literature
• Population not relevant
• Intervention/treatment not relevant
• Outcomes not relevant
• Outcomes have no clear evidence of clinical effectiveness
• Setting not relevant
• Not relevant to UK
• Incorrect study type
• Review article
• Duplicate reference

Organizational, behavioural and financial barriers

Our policy

The CKS literature searches take into consideration the following concepts, which are discussed at the initial scoping of the topic.

• Feasibility
  • Studies are selected depending on whether the intervention under investigation is available in the NHS and can be practically and safely undertaken in primary care.
• Organizational and Financial Impact Analysis
• Studies are selected and evaluated on whether the intervention under investigations may have an impact on local clinical service provision or national impact on cost for the NHS. The principles of clinical budget impact analysis are adhered to, evaluated and recorded by the author. The following factors are considered when making this assessment and analysis.
  • Eligible population
  • Current interventions
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  • Impact on other costs
  • Condition-related costs
  • In-direct costs and service impacts
  • Time dependencies
• Cost-effectiveness or cost-benefit analysis studies are identified where available. 

We also evaluate and include evidence from NICE accredited sources which provide economic evaluations of recommendations, such as NICE guidelines. When a recommended action may not be possible because of resource constraints, this is explicitly indicated to healthcare professionals by the wording of the CKS recommendation.

Declarations of interest

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Competing interests declared for this topic:

None.