Myeloma emergencies and supportive treatment

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Start with a syndrome map. Back pain needs neurological examination including power, reflexes, sensation, gait when safe and sphincter symptoms. Confusion needs glucose, oxygenation, infection, calcium, sodium, renal and medication review. Renal deterioration needs volume assessment, urinalysis, ultrasound, free light chains, calcium and a search for sepsis and nephrotoxins. Visual symptoms or mucosal bleeding need fundus examination and viscosity consideration. Known myeloma must not narrow the differential prematurely.

For suspected spinal cord or cauda equina compression, protect the spine when instability is possible, give analgesia and contact the MSCC service. NICE NG234 requires whole-spine MRI as soon as possible and within 24 hours. With neurological symptoms or signs, give dexamethasone 16 mg orally or equivalent parenterally, continue 16 mg daily while surgery or radiotherapy is planned, then taper. Seek haematology advice before steroids in unconfirmed radiological lymphoma or myeloma without neurological signs because diagnostic tissue may be altered.

Hypercalcaemia causes thirst, polyuria, dehydration, nausea, constipation, weakness, confusion and arrhythmia. Confirm corrected or ionised calcium, obtain ECG, renal, phosphate and magnesium and stop aggravating medicines. Restore volume carefully with isotonic crystalloid if depleted, avoiding fixed large volumes in cardiac or renal disease. For tumour-induced calcium at least 3.0 mmol/L, zoledronic acid 4 mg intravenously once over at least 15 minutes is licensed; severe renal impairment needs individual risk-benefit review. Treat the clone because calcium otherwise recurs.

Cast nephropathy is a renal and haematological emergency. Send serum free light chains urgently and quantify urine protein; a dipstick mainly detects albumin and can underrepresent light-chain burden. Correct dehydration without overload, treat calcium and sepsis, and stop avoidable nephrotoxins. NICE recommends immediately starting a bortezomib- and dexamethasone-based combination for untreated newly diagnosed myeloma-induced acute renal disease. Coordinate partner-drug renal adjustment and dialysis. Plasma exchange is not recommended for this indication.

Infection is a leading cause of harm. Immunoparesis can precede treatment, while steroids, anti-CD38 therapy, proteasome inhibitors and transplant add specific risks. Use NEWS2 and NICE NG253 while recognising that neutropenia or steroids may mute fever. Obtain blood and line cultures, lactate and focus-directed samples without delaying antibiotics in high-risk sepsis. Use the current local immunocompromised-host empirical regimen because resistance, allergy, colonisation and renal function determine choice. Reassess physiology, spectrum and source control repeatedly.

Bone and treatment support are acute and longitudinal. Stabilise impending fractures with orthopaedics and consider radiotherapy after stability review. NICE favours zoledronic acid for myeloma bone disease, with pamidronate or clodronate alternatives when unsuitable; arrange dental and renal assessment. Proteasome inhibitors warrant zoster prophylaxis and anti-CD38 treatment needs hepatitis B and transfusion preparation. Immunomodulatory drugs with steroids require VTE and formal pregnancy-prevention plans. Integrate multimodal analgesia, rehabilitation, vaccination, nutrition and palliative care, and reserve immunoglobulin replacement for selected recurrent serious infection with hypogammaglobulinaemia.

Key points

Treat the presenting syndrome and the clone in parallel: supportive measures alone cannot reverse continuing light-chain, marrow or skeletal injury.
Suspected malignant spinal cord compression needs urgent whole-spine MRI as soon as possible and always within 24 hours, with immobilisation when instability is possible.
NICE recommends dexamethasone 16 mg orally or equivalent parenterally immediately for neurological signs of cord compression, then 16 mg daily while surgery or radiotherapy is awaited.
Severe hypercalcaemia needs ECG, careful isotonic-fluid replacement when depleted, cessation of aggravating medicines and an intravenous bisphosphonate after renal assessment.
Myeloma-induced acute renal disease requires immediate bortezomib- and dexamethasone-based combination treatment under NICE NG35, alongside correction of volume, calcium, sepsis and nephrotoxins.
Do not use plasma exchange for myeloma-induced acute renal disease; urgent reduction of light-chain production is central, and dialysis follows ordinary emergency renal indications.
Clinical hyperviscosity with visual, mucosal or neurological findings requires urgent plasma exchange; do not wait for viscosity or omit systemic anti-myeloma follow-on therapy.
Zoledronic acid is first-line bone protection in NICE NG35 when suitable; arrange dental assessment, assess renal function and monitor calcium and osteonecrosis risk.
Immunomodulatory drugs with steroids need thrombosis assessment; NICE NG89 supports aspirin 75 or 150 mg or LMWH during therapy, selected by VTE and bleeding risk.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

High clonal and protein burden

Rapid plasma-cell proliferation and abundant monoclonal light chain drive renal tubular injury, hyperviscosity, marrow failure and metabolic instability.

Osteolytic bone disease

Myeloma cells stimulate osteoclasts and suppress osteoblasts, causing lytic lesions, vertebral collapse, fractures, hypercalcaemia and possible neural compression.

Immune and treatment effects

Immunoparesis, marrow suppression, steroids, targeted therapy and transplantation increase bacterial, viral and opportunistic infection risk while altering usual inflammatory signs.

Host and iatrogenic stressors

Dehydration, NSAIDs, contrast, infection, immobility and nephrotoxic or thrombogenic treatment can convert stable disease into acute decompensation.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Cast nephropathy
Filtered monoclonal free light chains bind uromodulin within distal tubules, forming obstructing inflammatory casts; dehydration and hypercalcaemia intensify renal injury.
2
Osteoclast-driven calcium release
Accelerated bone resorption releases calcium, causing nephrogenic diabetes insipidus, volume depletion, reduced filtration and self-reinforcing hypercalcaemic acute kidney injury.
3
Mechanical neural compression
Epidural plasmacytoma, vertebral collapse or retropulsed bone compresses spinal cord or cauda equina, making neurological recovery strongly time dependent.
4
Impaired antimicrobial defence
Suppressed polyclonal immunoglobulin, neutropenia, mucosal injury and cellular immune dysfunction reduce pathogen control and can produce fulminant infection with muted fever.
5
Viscosity and treatment complications
High monoclonal immunoglobulin impairs microcirculatory flow, while rapid treatment response can release potassium, phosphate and urate and precipitate tumour lysis.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Cord compression

Progressive back or radicular pain, weakness, sensory level, gait change or sphincter dysfunction demands immediate whole-spine assessment.

Hypercalcaemic dehydration

Thirst, polyuria, constipation, vomiting, confusion, weakness and short QT with volume loss create renal and cardiac risk.

Cast nephropathy

Abrupt renal decline with high involved free light chain and little albumin on dipstick suggests tubular light-chain obstruction.

Immunocompromised sepsis

Fever may be absent; rigors, hypotension, confusion, tachypnoea, oliguria or new oxygen requirement are sufficient for urgent assessment.

Hyperviscosity

Blurred vision, retinal change, headache, mucosal bleeding and neurological symptoms with high paraprotein require exchange, not observation.

Red flags requiring action

New severe back or radicular pain, weakness, sensory change, gait disturbance or bladder and bowel dysfunction is spinal cord or cauda equina compression until urgently excluded.
Confusion, dehydration, vomiting, constipation, shortened QT interval or arrhythmia with markedly raised corrected or ionised calcium requires same-day treatment and cardiac monitoring.
Rapid creatinine rise, oliguria, very high involved free light chain or concurrent hypercalcaemia suggests cast nephropathy and needs immediate clone-reduction planning.
Fever, hypothermia, rigors, confusion, hypotension, tachypnoea or new oxygen requirement during myeloma treatment requires urgent sepsis assessment even without neutropenia.
Headache, blurred vision, retinal venous engorgement, mucosal bleeding or neurological change with a large paraprotein suggests symptomatic hyperviscosity and urgent plasma exchange.
A painful limb deformity, inability to weight bear, new vertebral collapse or impending long-bone fracture needs urgent orthopaedic and imaging assessment.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
First-line emergency laboratory panelFirst stepFirst line
Why
Identify immediately reversible metabolic, renal, infectious and marrow threats.
Interpretation and limitations
Send FBC, film, renal, corrected and ionised calcium as appropriate, phosphate, magnesium, urate, LDH, liver, CRP, coagulation and lactate or cultures when infection is possible.
02
First-line: serum free light chains and clonal markersFirst line
Why
Quantify the nephrotoxic clone and establish an urgent response baseline.
Interpretation and limitations
Use involved chain, ratio, SPEP and immunofixation; a rapid involved-chain fall is central in cast nephropathy, but results must not delay stabilisation.
03
Gold standard acute cord imaging: whole-spine MRIGold standard
Why
Locate epidural disease, cord or cauda equina compression and vertebral instability.
Interpretation and limitations
Perform as soon as possible and within 24 hours; use CT when MRI is contraindicated and discuss further imaging with the specialist service.
04
Renal mechanism assessment
Why
Distinguish casts from obstruction, sepsis, medicine injury, amyloid and glomerular disease.
Interpretation and limitations
Combine urine microscopy, quantified albumin and protein, ultrasound, free light chains and medication review; renal biopsy can resolve management-changing uncertainty.
05
Viscosity and ophthalmic assessment
Why
Support diagnosis and establish response in suspected hyperviscosity.
Interpretation and limitations
Retinal venous engorgement or haemorrhage and clinical symptoms can justify exchange before viscosity returns; follow the same laboratory method after treatment.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Metastatic solid cancer

Lytic lesions, cord compression and hypercalcaemia can arise from solid malignancy; biopsy and clonal studies establish the responsible tumour when history is uncertain.

Primary hyperparathyroidism

Hypercalcaemia with inappropriately raised parathyroid hormone suggests primary endocrine disease rather than myeloma-driven osteolysis, although both may coexist.

Other acute kidney injury

Sepsis, obstruction, medication toxicity, glomerulonephritis and amyloid can cause renal failure; urinalysis, imaging and selective biopsy distinguish mechanisms.

Non-malignant spinal emergency

Epidural abscess, disc prolapse, vertebral infection and osteoporotic collapse can mimic myeloma compression and still require urgent whole-spine imaging.

Alternative encephalopathy

Sepsis, uraemia, medication toxicity, stroke and hyponatraemia can cause confusion; do not attribute altered consciousness to calcium without simultaneous assessment.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01New neurological deficitProtect cord functionFirst stepBack pain accompanies weakness, sensory, gait or sphincter change.

1Immobilise if instability is suspected, give analgesia, document neurology and contact the MSCC service immediately.
2Give dexamethasone 16 mg orally or equivalent parenterally and arrange whole-spine MRI within 24 hours.
3DefinitiveCoordinate urgent surgery, radiotherapy or systemic treatment, then taper steroid after definitive treatment starts.

02Severe hypercalcaemiaRestore volume and stop calcium releaseSymptomatic or markedly raised corrected or ionised calcium is confirmed.

1Obtain ECG and renal-electrolyte baseline, stop aggravating medicines and replace fluid carefully if depleted.
2Give a renal-appropriate intravenous bisphosphonate; use specialist rescue such as calcitonin or dialysis when physiology requires it.
3Monitor calcium, phosphate, magnesium, fluid balance and renal function while starting anti-myeloma therapy.

03Myeloma acute kidney injuryReduce light chains immediatelyRapid renal decline is plausibly caused by untreated newly diagnosed myeloma.

1Correct volume, calcium and infection, stop nephrotoxins and send urgent free light chains, urine studies and renal imaging.
2Immediately start a bortezomib- and dexamethasone-based combination with haematology and renal dose review.
3Dialyse for conventional emergency indications; do not use plasma exchange for myeloma-induced acute renal disease.

04Clinical hyperviscosityExchange first and suppress productionVisual, mucosal bleeding or neurological features accompany a high intact paraprotein.

1Contact apheresis urgently, send viscosity and clonal studies, examine fundi and avoid unnecessary red-cell transfusion.
2Perform therapeutic plasma exchange without awaiting a numerical threshold.
3Start systemic anti-myeloma therapy promptly because exchange alone produces temporary protein reduction.

Key medicines and prescribing safety5 treatments · regimens, roles and cautions

First-line corticosteroid to reduce oedema and protect neurological function in MSCC under NICE NG234.

Dexamethasone for malignant cord compression

Give 16 mg orally immediately, or the equivalent parenteral dose, for neurological symptoms or signs; continue 16 mg orally or parenterally each day while surgery or radiotherapy is awaited, then taper gradually after definitive treatment starts.

Monitor glucose, infection, mood, weakness and gastrointestinal risk and prescribe proton-pump-inhibitor protection. Stop if imaging excludes MSCC. Seek haematology advice before steroid in radiologically suspected but unconfirmed lymphoma or myeloma without neurological signs because diagnosis may be altered.

First-line NICE-supported bisphosphonate when suitable for acute tumour-induced hypercalcaemia and longitudinal myeloma bone protection.

Zoledronic acid

For tumour-induced hypercalcaemia with corrected calcium at least 3.0 mmol/L, give 4 mg intravenously once over at least 15 minutes after volume assessment. For skeletal-event prevention, 4 mg intravenously every 3–4 weeks is licensed, with renal modification.

Check creatinine, calcium, phosphate, magnesium, vitamin D and dental status. Severe renal impairment needs individual risk-benefit review; adapt repeated dosing for deterioration. Counsel on jaw pain and avoid invasive dental work when possible. Do not add calcium during active hypercalcaemia.

Rapid first-line reduction of nephrotoxic free-light-chain production under NICE NG35.

Bortezomib-dexamethasone renal rescue

Start immediately under a haematology centre combination for untreated newly diagnosed myeloma-induced acute renal disease. One licensed bortezomib schedule is 1.3 mg/m² subcutaneously or intravenously on days 1, 4, 8 and 11 of a 21-day cycle, at least 72 hours apart; partners follow the selected protocol.

No starting reduction is required solely for renal impairment, but administer after dialysis and adjust partner medicines. Monitor neuropathy, hypotension, platelets, infection, hepatic function and tumour lysis. Give antiviral prophylaxis and hold or reduce for significant neuropathy or toxicity.

Prevention of herpes simplex and zoster reactivation during treatment-associated cellular immune suppression.

Aciclovir prophylaxis

A common myeloma centre regimen with bortezomib or anti-CD38 therapy is aciclovir 400 mg orally twice daily during treatment and for the protocol-defined period afterwards; reduce dose or extend interval according to renal function.

Confirm local duration because immunosuppression varies. Maintain appropriate hydration without overload, adjust for eGFR and monitor neurotoxicity and crystal-associated renal injury, especially during acute kidney injury.

Prevention of treatment-amplified venous thromboembolism throughout the thrombogenic regimen.

Immunomodulatory-drug thromboprophylaxis

During thalidomide, lenalidomide or pomalidomide with steroids, NICE NG89 supports aspirin 75 mg or 150 mg orally daily or prophylactic-dose LMWH; select and dose LMWH by product, body weight and renal function while the risk regimen continues.

Reassess prior VTE, immobility, obesity, steroid intensity, thrombocytopenia, renal impairment and bleeding. Aspirin is insufficient for some high-risk patients; LMWH may need renal or platelet modification. Pregnancy requires obstetric-haematology selection.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Permanent neurological disability

Delayed spinal decompression can leave irreversible weakness, sphincter dysfunction, immobility, pressure injury, venous thrombosis and loss of independence.

Dialysis-dependent kidney failure

Prolonged cast nephropathy or combined toxic, calcium and septic injury can prevent renal recovery despite later haematological response.

Arrhythmia and circulatory collapse

Severe calcium disturbance, sepsis, hyperviscosity and treatment-related electrolyte shifts can cause malignant arrhythmia, shock and death.

Recurrent infection

Immunoparesis and cumulative treatment produce repeated respiratory, bloodstream, zoster and opportunistic infection, treatment interruption and progressive frailty.

Skeletal morbidity and thrombosis

Fracture, chronic pain, immobility and immunomodulatory therapy cause functional decline and venous thromboembolism unless prevention is individualised.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Repeat neurological examination and document power, sensory level, gait and sphincter function while awaiting and after definitive MSCC treatment.
During hypercalcaemia track ECG when severe, calcium, phosphate, magnesium, fluid balance, weight and renal function; anticipate delayed bisphosphonate effect and later hypocalcaemia.
During renal rescue measure creatinine, urine output, potassium, bicarbonate, calcium, phosphate and involved free light chain frequently enough to identify response and dialysis indications.
Maintain a transfusion plan including daratumumab interference and any irradiation requirement from transplant or prior therapy.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Dipstick can undercall casts

Urine dipsticks mainly detect albumin, so severe light-chain proteinuria and cast nephropathy may coexist with deceptively modest dipstick protein.

MRI covers the whole spine

Myeloma lesions can be multiple and the symptomatic level misleading; whole-spine MRI identifies non-contiguous compression and guides definitive treatment.

Calcium and kidney injury amplify

Hypercalcaemia causes polyuria and dehydration, worsening filtration and tubular light-chain concentration; reversing both mechanisms is essential.

Exchange is mechanism specific

Plasma exchange rapidly treats hyperviscosity but is not recommended for myeloma-induced acute renal disease; do not generalise one procedure across complications.

11Common pitfallsFrequent interpretation and management errors.

01
Do not wait for bladder retention or paraplegia before treating suspected spinal cord compression as an emergency.
02
Do not give indiscriminate large-volume fluid for hypercalcaemia without repeated cardiac, renal and congestion assessment.
03
Do not use plasma exchange for myeloma-induced acute renal disease; use immediate clone reduction and standard renal support.
04
Do not assume oliguria is cast nephropathy without checking sepsis, obstruction, calcium, volume and medicines.
05
Do not start bisphosphonate without renal and dental assessment or continue unchanged through significant renal deterioration.
06
Do not prescribe an immunomodulatory drug and steroid without VTE, pregnancy-prevention and infection plans.