Hematology, Oncology & Immunology · Topic 19 of 26

Multiple Myeloma

Hematology-oncology · plasma cell disorders

Multiple Myeloma

Clonal plasma cells that break bone and kidneys: think CRAB — calcium, renal failure, anemia, bone lesions — and order SPEP with free light chains.

Key numbers

≥ 10% clonal plasma cells plus damagemarrow plasma cells ≥ 10%

CRAB: calcium, renal, anemia, boneCa > 11 · Cr > 2 · Hb < 10

01 · Defined byCRAB: calcium, renal, anemia, bone

Calcium > 11 mg/dL (or > 1 above normal); creatinine > 2 mg/dL or CrCl < 40 mL/min; hemoglobin < 10 g/dL (or > 2 below normal); any lytic lesion on X-ray, CT or PET-CT.

02 · DoSPEP plus serum free light chains

Screen with serum protein electrophoresis plus serum immunofixation and serum free light chains (with 24-hour urine electrophoresis and immunofixation) — SPEP alone misses light-chain-only myeloma (15–20%); confirm with bone marrow biopsy and FISH.

03 · Watch forCast nephropathy: hydrate, avoid nephrotoxins

Kidney injury is usually light-chain cast nephropathy or hypercalcemia: hydrate to urine output above 2 L/day, avoid nephrotoxins and IV contrast with dehydration, and start bortezomib-based therapy quickly to lower light chains.

Presentation

What you'll see

Clues: bone pain, anemia, high protein, rouleauxSuspect myeloma at age over 40 with persistent back or rib pain (worse at rest or night), normocytic anemia with rouleaux, high total protein, low anion gap, hypercalcemia, unexplained renal failure or recurrent infections.

Diagnosis & monitoring

Work-up

≥ 10% clonal plasma cells plus damage must knowMultiple myeloma = clonal bone marrow plasma cells ≥ 10% (or a biopsy-proven plasmacytoma) plus at least one myeloma-defining event: CRAB end-organ damage or a SLiM biomarker of malignancy (IMWG criteria).

SLiM: treat even without CRABSLiM biomarkers define active myeloma without CRAB: ≥ 60% clonal marrow plasma cells, involved/uninvolved free light chain ratio ≥ 100 (involved ≥ 100 mg/L), or more than one focal MRI lesion ≥ 5 mm.

Do right now

In this order

First moves

Hypercalcemia: IV saline, then zoledronic acid

→

Cast nephropathy: hydrate, avoid nephrotoxins

→

SPEP plus serum free light chains

Why each step

Hypercalcemia: IV saline, then zoledronic acidMyeloma hypercalcemia (about 10% at diagnosis) is treated with IV saline, then an IV bisphosphonate — preferably zoledronic acid — after rehydration, sometimes with calcitonin or prednisone; denosumab suits severe renal failure (see Hypercalcemia).

Cast nephropathy: hydrate, avoid nephrotoxinsKidney injury is usually light-chain cast nephropathy or hypercalcemia: hydrate to urine output above 2 L/day, avoid nephrotoxins and IV contrast with dehydration, and start bortezomib-based therapy quickly to lower light chains.

SPEP plus serum free light chainsScreen with serum protein electrophoresis plus serum immunofixation and serum free light chains (with 24-hour urine electrophoresis and immunofixation) — SPEP alone misses light-chain-only myeloma (15–20%); confirm with bone marrow biopsy and FISH.

Management

Orders

Image bones with low-dose CT, PET-CT or MRIWhole-body low-dose CT, PET-CT or MRI is more sensitive than a skeletal survey for punched-out lytic lesions; a bone scan is usually unhelpful, and osteoporosis or compression fractures alone do not meet the bone criterion.

Monthly zoledronic acid or denosumab for boneGive most patients with lytic lesions or osteopenia a monthly IV bisphosphonate (zoledronic acid or pamidronate) or denosumab (not renally cleared); both can cause osteonecrosis of the jaw, so dental care comes first.

Anti-CD38 plus bortezomib-based inductionInitial therapy combines an anti-CD38 antibody (daratumumab or isatuximab) with bortezomib, dexamethasone and often lenalidomide; fit patients may then have autologous stem cell transplant, which prolongs progression-free survival.

Lenalidomide needs VTE prophylaxisLenalidomide (especially with dexamethasone) markedly raises DVT, PE, MI and stroke risk — antithrombotic prophylaxis is recommended; bortezomib's dose-limiting toxicity is peripheral neuropathy but it needs no renal dose change.

Red flags & don'ts

Avoid harm

Vertebral collapse can compress the cord complicationPathologic fractures are common, and vertebral collapse or plasmacytoma can cause spinal cord compression and paraplegia — new back pain with deficits needs emergent spine MRI and dexamethasone (see Malignant Spinal Cord Compression).

Infection risk: antiviral prophylaxis and vaccines complicationLow uninvolved immunoglobulins and therapy raise infection risk: give acyclovir-class prophylaxis with proteasome inhibitors, anti-CD38 antibodies, bispecifics or CAR-T; vaccinate (no live vaccines); IVIG only for recurrent infections with low immunoglobulins.

Hyperviscosity in a few — plasma exchange complicationHyperviscosity complicates 2–6% of myeloma, usually high-level IgA or IgG3 paraprotein; symptomatic patients need plasma exchange (see Hyperviscosity & Leukostasis).

MGUS or multiple myeloma?

Commonly confused

Clonal marrow plasma cells	Under 10%
Serum M-protein	Under 3 g/dL
CRAB damage or SLiM biomarker	None

More detail

Reference

Show 6 reference facts

Revised ISS: stage I = beta-2 microglobulin < 3.5 mg/L, albumin ≥ 3.5 g/dL, normal LDH and standard-risk FISH; stage III = beta-2 microglobulin ≥ 5.5 mg/L with high-risk FISH or high LDH.

High-risk cytogenetics include t(4;14), t(14;16), t(14;20), del(17p)/TP53 and 1q gain; t(11;14) predicts response to venetoclax.

The M-protein is IgG in about 50–55% and IgA in about 20%; 15–20% secrete only light chains (Bence Jones protein), which SPEP can miss.

AL amyloidosis develops in about 10% of myeloma patients, usually with lambda light chains; nephrotic-range proteinuria and carpal tunnel syndrome are clues.

Light-chain proximal tubulopathy can cause Fanconi syndrome — hypokalemia, hypophosphatemia and metabolic acidosis — and about 10% of patients need dialysis at diagnosis.

Median age at diagnosis is about 70, prevalence in Black patients is twice that in White patients, and median survival now exceeds 10 years.

Pearl

CRAB: Calcium high, Renal failure, Anemia, Bone lesions — the end-organ damage that turns a plasma cell clone into myeloma.

Sources · Merck Manual Professional — Multiple Myeloma · International Myeloma Foundation — IMWG criteria for the diagnosis of multiple myeloma · Recent updates in the diagnosis and management of kidney diseases in multiple myeloma. Indian J Nephrol 2025 · Revlimid (lenalidomide) prescribing information — DailyMed (boxed warning: venous and arterial thromboembolism) · Hyperviscosity syndrome in paraprotein secreting conditions including Waldenström macroglobulinemia. Front Oncol 2020;10:815 · Starter sheet built from the verified AGACNP fact map (facts reviewed 2026-10-15).