Multiple myeloma — recognition, workup, and GP shared care

Multiple myeloma is a cancer of plasma cells — the antibody-producing cells in the bone marrow. Abnormal plasma cells proliferate and produce a monoclonal immunoglobulin (paraprotein or M-protein), crowding out normal blood production and causing damage to bone, kidneys, and immune function. It sits on a spectrum from precursor states (MGUS, smouldering myeloma) through to active disease requiring treatment.

Australia records approximately 2,500 new diagnoses per year. The median age at diagnosis is 70, and it affects men slightly more than women. The GP’s primary contribution is recognising the pattern of symptoms that suggests myeloma — persistent back or bone pain, unexplained anaemia, renal impairment, or recurrent serious infection in an older adult — and arranging the right initial workup before referring urgently to haematology.

A. Core clinical — the AU general-practice framework

How myeloma presents

The most common presenting symptom is persistent bone or back pain, present in approximately 70% of patients at diagnosis. The pain is often worse at rest and may represent vertebral compression fractures from lytic bone disease. A sudden severe localised pain in an older adult can represent a pathological fracture.

Other common presentations:

• Fatigue and anaemia (normocytic, normochromic) from marrow infiltration
• Recurrent serious infections — particularly pneumonia or sinusitis from encapsulated organisms (Streptococcus pneumoniae, Haemophilus influenzae) due to impaired humoral immunity
• Unexplained renal impairment — from light-chain cast nephropathy, hypercalcaemia, or NSAIDs given for bone pain
• Hypercalcaemia symptoms — polyuria, polydipsia, constipation, confusion, abdominal pain
• Incidental discovery of a monoclonal protein on protein electrophoresis requested for another reason (raised total protein, elevated ESR)

Less common presentations: pathological fracture without known trauma, peripheral neuropathy (from amyloid deposition), hyperviscosity symptoms (headache, blurred vision, confusion with very high paraprotein levels).

History

• Bone and musculoskeletal pain — exact location, character, duration. Night pain and rest pain in an older adult with unexplained anaemia should trigger myeloma workup.
• Constitutional symptoms — weight loss, fatigue
• Infection history — recurrent pneumonia, sinusitis, urinary tract infections in the preceding 12 months
• Renal symptoms — foamy urine, reduced urine output, oedema
• Hypercalcaemia symptoms — excessive thirst and urination, constipation, confusion
• Neurological — new leg weakness, sensory change, or bladder/bowel dysfunction (spinal cord compression — emergency)
• Drug history — NSAIDs, ACE inhibitors, ARBs, IV contrast (all nephrotoxic in the myeloma setting)
• Family history — multiple myeloma, MGUS, lymphoid malignancy

Examination

• General appearance — pallor, cachexia
• Vital signs including postural blood pressure
• Musculoskeletal — spinal percussion tenderness, any palpable bony mass
• Neurological — mandatory: lower limb power, sensation, reflexes, bladder percussion (UMN signs below a level = cord compression until proven otherwise)
• Cardiovascular — raised JVP, oedema (cardiac amyloidosis)
• Mucocutaneous — macroglossia (amyloid), purpura, periorbital ecchymosis
• Lymphadenopathy and organomegaly — absence favours myeloma over lymphoma

Investigations — GP-ordered initial workup

Per eTG, Myeloma Australia, and eviQ, the initial GP workup includes:

1. Full blood count + film — normocytic anaemia; rouleaux (red cell stacking from high protein) is a visual prompt
2. Urea, electrolytes, creatinine, corrected calcium — renal impairment and hypercalcaemia are CRAB criteria
3. LFTs, albumin, total protein — a high total protein with low or normal albumin indicates a high globulin, raising suspicion
4. Serum protein electrophoresis (SPEP) + immunofixation — detects and characterises the monoclonal band (IgG, IgA, IgM, or light chain only)
5. Serum free light chains (kappa and lambda) + ratio — abnormal ratio confirms clonal light-chain production; essential for non-secretory and light-chain-only variants
6. 24-hour urine protein or random urine with immunofixation — Bence Jones protein (light chains in urine indicate risk of renal cast nephropathy)
7. Quantitative immunoglobulins (IgG, IgA, IgM) — functional hypogammaglobulinaemia despite raised total protein
8. Beta-2-microglobulin and LDH — prognostic factors; part of the International Staging System
9. ESR — often markedly elevated; complements clinical picture
10. Plain X-ray of any symptomatic bone area — lytic lesions are the initial imaging in general practice; whole-body low-dose CT or MRI are used for staging at haematology level

Bone marrow biopsy (plasma cell percentage, cytogenetics by FISH, flow cytometry) is performed by haematology — not in general practice.

Plasma cell disorder spectrum

Entity	Key features	Management
MGUS	M-protein under 30 g/L + BM plasma cells under 10% + no CRAB/SLiM	Surveillance only — ~1%/year progression
Smouldering myeloma	M-protein ≥30 g/L OR BM plasma cells 10–60% + no CRAB	Surveillance unless high-risk
Symptomatic myeloma	≥10% clonal plasma cells + ≥1 CRAB or SLiM criterion	Treatment required
Plasma cell leukaemia	Circulating plasma cells ≥20% OR ≥2×10⁹/L	Aggressive treatment urgently

B. Treatment overview (haematology-led)

Treatment decisions belong entirely to haematology. The role documented here is to help the GP understand what the patient is receiving and why.

Per the landmark 2024 review by Rajkumar in the American Journal of Haematology, the treatment paradigm has shifted to quadruplet induction therapy:

Transplant-eligible (typically ≤70 years, good functional status):

• Induction: Dara-VRd (daratumumab + bortezomib + lenalidomide + dexamethasone) — based on GRIFFIN and PERSEUS RCT data showing superior MRD-negativity and progression-free survival
• Autologous stem cell transplant (ASCT) after induction
• Lenalidomide maintenance until progression or intolerance

Transplant-ineligible:

• VRd (bortezomib + lenalidomide + dexamethasone) × 8–12 cycles then lenalidomide maintenance, OR
• DRd (daratumumab + lenalidomide + dexamethasone) until progression

Relapsed/refractory:

• Carfilzomib, pomalidomide, isatuximab, selinexor, and others — various combinations
• CAR-T cell therapy (idecabtagene vicleucel, ciltacabtagene autoleucel) — TGA-approved; PBS via Section 100 Highly Specialised Drugs for eligible patients at specialist centres
• Bispecific antibodies (teclistamab, talquetamab) — available at selected centres; PBS access being established

All major agents require PBS Authority — this is handled by the haematologist. The GP does not prescribe these agents in routine shared care.

C. GP shared-care responsibilities

Supportive care and complication surveillance

Bone protection:

• Monthly IV zoledronic acid 4 mg or monthly subcutaneous denosumab 120 mg — reduces fracture risk; continue for at least 12 months
• Dental review before starting bisphosphonate — reduces osteonecrosis of the jaw risk
• Calcium and vitamin D supplementation alongside bisphosphonate

Infection prevention: Per eviQ and the Australian immunisation handbook, ensure:

• Pneumococcal vaccines (both PCV13 and 23vPPV, timing per haematology guidance)
• Annual influenza vaccine
• COVID-19 vaccine and boosters
• RSV vaccine if aged 75 and over
• Shingles vaccine — recombinant (Shingrix, non-live) preferred; avoid live vaccines during active chemotherapy or immunosuppression
• Consider intravenous immunoglobulin (IVIG) if recurrent severe infections — PBS Section 100 via NBA criteria

Venous thromboembolism prophylaxis: During lenalidomide or pomalidomide therapy, VTE prophylaxis is required. The exact agent (aspirin, DOAC, or LMWH) is specified in the haematology management plan based on individual VTE risk score.

Renal protection:

• Avoid NSAIDs and ibuprofen-containing products (including many OTC pain preparations) — this is a standing instruction for all myeloma patients
• Use care with IV contrast; alert the radiology department of myeloma status
• Maintain adequate hydration, particularly during high-dose chemotherapy cycles

Pain management:

• WHO analgesic ladder approach; paracetamol as baseline
• Opioids as required, with SafeScript checking for S8 prescriptions
• Radiotherapy for focal bone pain refractory to systemic analgesia — liaise with radiation oncology

Monitoring bloods during shared care (frequency per haematology plan):

• FBC, UEC, corrected calcium, M-protein, and free light chain ratio — typically every three months in stable maintenance, more frequently during active treatment

Psychological support

A myeloma diagnosis profoundly affects quality of life. The GP’s Mental Health Care Plan (items 2715 and 2717) can access psychology for cancer-related anxiety and depression adjustment. Myeloma Australia and the Leukaemia Foundation provide peer support, written information, and nurse coordinators.

D. Australian operations

MBS items:

• Standard consultations: Level B (item 23), Level C (item 36), Level D (item 44)
• GP Chronic Condition Management Plan: item 965 (preparation), item 967 (review) — myeloma on ongoing therapy qualifies
• Mental Health Care Plan: items 2715/2717 for adjustment disorder or cancer-related anxiety
• PET-CT: items 61653/61678 — rebatable for myeloma staging and response assessment
• Telehealth: items 91790/92029 for stable shared-care reviews in established patients
• ATSI Health Assessment: item 715

PBS medicines: All major myeloma-specific agents (bortezomib, lenalidomide, daratumumab, and newer drugs) are PBS Authority Required Section 100 via haematology prescribing. The GP’s PBS role in myeloma shared care centres on bisphosphonates, antiemetics, analgesics, and supportive medications — these are standard schedule prescriptions. Zoledronic acid (PBS Authority for bone metastases) and denosumab (PBS Authority for myeloma bone disease) are prescribed by haematology but the infusions are often administered through shared-care facilities.

E. Special populations

Aboriginal and Torres Strait Islander Australians. Limited registry-specific data exist but late presentation is a recognised concern across cancer diagnoses. The ATSI Health Assessment (item 715) provides an annual opportunity to investigate unexplained anaemia, renal impairment, or bone pain in older Aboriginal and Torres Strait Islander adults. Coordinate with Aboriginal Community Controlled Health Organisations and Aboriginal Health Workers.

Older adults (>75 years). Many older patients are not suitable for autologous stem cell transplant. Transplant-ineligible regimens (VRd or DRd) remain highly effective. Dose modification for renal impairment and frailty is standard. The GP plays a larger role in overall geriatric coordination — falls risk with bone disease, polypharmacy review, advance care planning.

Patients with CKD. Renal impairment from light-chain cast nephropathy can be partly reversed with effective anti-myeloma therapy. During shared care, protect residual renal function: avoid NSAIDs and nephrotoxic antibiotics; flag myeloma status before any contrast imaging; maintain adequate hydration.

When to escalate

Call 000 or arrange same-day transfer to hospital:

• New leg weakness, sensory level, or bladder/bowel dysfunction — spinal cord compression requires same-day MRI, IV dexamethasone, and radiation oncology assessment
• Corrected calcium >3.0 mmol/L with symptoms (confusion, severe constipation, severe vomiting) — hypercalcaemia of malignancy requires IV saline and bisphosphonate in hospital
• Fever ≥38.5°C in a patient receiving chemotherapy — neutropenic sepsis until proven otherwise; lower threshold than for the general population
• Sudden severe bone pain — pathological fracture needs imaging and analgesia; vertebral fracture with neurological signs is an emergency
• Confusion, blurred vision, or neurological change — consider hyperviscosity (with very high paraprotein) or hypercalcaemia

Refer back to haematology promptly (within days):

• Rising M-protein on surveillance
• New CRAB feature in a patient being surveilled for MGUS or smouldering myeloma
• Any new or worsening renal impairment during treatment

What this article is and is not

This is general health information drawn from Therapeutic Guidelines, Myeloma Australia, eviQ Cancer Institute NSW, the International Myeloma Working Group criteria, and the Rajkumar 2024 update. It is not personal medical advice and does not create a doctor–patient relationship. All treatment decisions are made by the specialist haematology team. Individual circumstances, comorbidities, and treatment response determine the actual management plan for each patient.

For Australian consumer resources: Myeloma Australia, Leukaemia Foundation, Cancer Council Australia — 13 11 20, HealthDirect.

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Sources cited

1. International Myeloma Working Group — Diagnostic Criteria 2014
2. Rajkumar SV — Multiple myeloma 2024 update (AJH 2024)
3. Myeloma Australia — Clinical practice resources
4. eviQ — Myeloma protocols (Cancer Institute NSW)
5. Therapeutic Guidelines — Myeloma
6. Australian Medicines Handbook
7. TGA — CAR-T cell therapy and PBS Authority listings
8. Cancer Council Australia
9. Leukaemia Foundation
10. HealthDirect — Multiple myeloma