Multiple Myeloma

Meet the patient

A 69-year-old man arrives with three months of lower-back pain, constipation and confusion. His bloods show a corrected calcium of 3.1 mmol/L, a creatinine of 220 micromol/L, a haemoglobin of 88 g/L, and an ESR of 120 mm/h with rouleaux on the film. A skull X-ray ordered "for the headaches" shows punched-out lytic lesions.[1]

He has walked in with the full CRAB tetrad — and the two questions that decide his next 24 hours are the two that decide every myeloma: is this myeloma? (a paraprotein screen and a marrow biopsy answer it) and is his kidney salvageable? (aggressive hydration and bortezomib decide it).[1][3]

The plasma-cell clone and the CRAB it causes

Multiple myeloma is a malignant clonal neoplasm of terminally differentiated B-cells (plasma cells) that accumulates in the bone marrow and secretes a monoclonal immunoglobulin (the paraprotein or M-protein) and/or free light chains. The clone is a post-germinal-centre B-cell that has undergone somatic hypermutation and class-switching but acquired transforming lesions.[1]

The disease harms through three linked mechanisms: infiltration of the marrow by plasma cells (anaemia, cytopenias); secretion of monoclonal protein and cytokines (renal cast nephropathy, hyperviscosity, bone destruction, immune paresis); and cytokine-driven uncoupled bone turnover (lytic lesions, hypercalcaemia, fractures). End-organ damage is the CRAB mnemonic — hyperCalcaemia, Renal impairment, Anaemia, Bone lesions — and myeloma is distinguished from its precursors (MGUS, smouldering myeloma) by the presence of that damage or a myeloma-defining biomarker.[1][3]

Myeloma is the second commonest haematological malignancy after non-Hodgkin lymphoma, predominantly affecting older adults (median age about 70). Proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies — now joined by bispecific antibodies and anti-BCMA CAR-T — have transformed a previously uniformly fatal disease into a chronic, relapsing-remitting condition.[1]

[1]

The spectrum — MGUS, smouldering, symptomatic

Myeloma sits at the symptomatic end of a plasma-cell dyscrasia spectrum distinguished by the paraprotein load, the marrow plasma-cell percentage, and the presence or absence of end-organ damage or a biomarker.[1][3]

[1]

By secreted paraprotein type: IgG is the commonest (about 50 percent), then IgA (about 20 percent). Light-chain-only (Bence Jones) myeloma is 15 to 20 percent — there is no intact M-band on SPEP, so it is easily missed if only a serum SPEP is sent. The rare IgD and IgE and the non-secretory forms (1 to 2 percent) are diagnosed by marrow and imaging and monitored with serum free light chains.[1]

The related plasma-cell disorders that examiners test by their distinguishing features:[1]

• Solitary plasmacytoma of bone — a single clonal plasma-cell tumour of the skeleton with no systemic disease; treated with radiotherapy with curative intent, though about half progress to myeloma within 10 years.
• Extramedullary plasmacytoma — a soft-tissue plasma-cell tumour (commonly upper respiratory tract); radiotherapy, excellent prognosis.
• POEMS syndrome — polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (almost always lambda), skin changes, plus osteosclerotic bone lesions and a markedly raised VEGF.
• AL amyloidosis — light chains misfolding as amyloid deposited in tissues (heart, kidney, liver, nerves); macroglossia, periorbital purpura, nephrotic-range proteinuria, restrictive cardiomyopathy.[1]

Who gets it

Multiple myeloma is about 1 to 2 percent of all cancers and 10 to 15 percent of haematological malignancies — the second commonest haematological malignancy after NHL. The median age is about 69 to 70, with under 2 percent before 40. There is a slight male predominance and roughly twice the incidence in people of African ancestry, who also present younger.[1]

Recognised risk factors: increasing age; male sex and African ancestry; family history (roughly twofold in first-degree relatives); obesity; and prior MGUS — the obligate precursor in essentially all cases, present in over 3 percent of people over 50 and progressing at about 1 percent per year.[1]

[1]

The mechanism — why each CRAB feature happens

The malignant clone is supported by a marrow microenvironment: stromal cells secrete interleukin-6, VEGF and other cytokines and bind the myeloma cells via adhesion molecules, activating NF-κB, STAT3 and PI3K/AKT survival pathways that drive proliferation and drug resistance. Each CRAB feature has a distinct mechanistic basis an examiner will probe.[1]

Bone destruction (and the hypercalcaemia of C) — plasma cells and stromal cells secrete RANKL, which activates osteoclasts, while DKK1 suppresses osteoblasts. The result is uncoupled bone resorption without matching formation: punched-out lytic lesions, pathological fractures, and hypercalcaemia as calcium leaches from resorbed bone. The "raindrop" or "punched-out" skull appearance is the classic sign.[1]

Renal damage (R) — excess monoclonal free light chains are filtered, taken up by proximal tubular cells, and precipitate as obstructive tubular casts with a giant-cell reaction (myeloma cast nephropathy), the commonest myeloma kidney lesion. AL amyloidosis, light-chain deposition disease, hypercalcaemic nephropathy, uric-acid nephropathy, dehydration and nephrotoxic drugs (NSAIDs, iodinated contrast) compound it. The combination of light-chain toxicity and a second insult is what precipitates the AKI.[1]

Anaemia (A) — a normocytic, normochromic anaemia from marrow infiltration, renal anaemia (less erythropoietin), cytokine-mediated suppression (hepcidin), and sometimes folate or iron deficiency.[1]

Immune paresis and recurrent infection — the heavy paraprotein load suppresses normal polyclonal immunoglobulin production; neutropenia compounds the risk. Infections are typically with encapsulated respiratory organisms (Streptococcus pneumoniae, Haemophilus influenzae) and Gram-negatives, and herpes zoster reactivation is common on proteasome inhibitors.[1]

Cytogenetics — FISH, not karyotyping

Myeloma divides into two broad cytogenetic groups. Hyperdiploid myeloma (odd-numbered trisomies) is generally standard-risk. Non-hyperdiploid myeloma includes the IgH translocations at 14q32 — most importantly t(4;14), t(14;16) and t(14;20). The high-risk lesions — del(17p)/TP53 loss, t(4;14), t(14;16) and gain(1q) — are detected by FISH on CD138-purified plasma cells.[2]

How it walks in — bone pain, CRAB, the emergencies

The typical presentation is an older adult with persistent bone pain (back, ribs, long bones — often worse on movement and at night), fatigue (anaemia), recurrent infections, and symptoms of hypercalcaemia or renal failure (thirst, polyuria, constipation, confusion, nausea). Bone pain is the single commonest presenting symptom; up to a third are diagnosed after a pathological fracture, and a meaningful minority are picked up incidentally through a raised ESR or an M-band.[1]

The CRAB features in detail:[1]

• C — hyperCalcaemia — thirst, polyuria, dehydration, constipation, abdominal pain, confusion (the "stones, bones, groans, moans"). Corrected calcium over 2.75 mmol/L (11 mg/dL); severe hypercalcaemia is an emergency.
• R — Renal impairment — usually cast nephropathy; AKI or progressive CKD, often precipitated by dehydration, iodinated contrast or NSAIDs. The urine is negative for albumin on dipstick despite proteinuria — dipsticks detect albumin, not light chains.
• A — Anaemia — normocytic, normochromic.
• B — Bone lesions — punched-out lytic lesions (skull "raindrop", spine, pelvis, ribs, proximal long bones), diffuse osteopenia, pathological fractures.[1]

AL amyloidosis features that may accompany myeloma: macroglossia, periorbital purpura ("raccoon eyes"), nephrotic-range proteinuria, restrictive cardiomyopathy (raised JVP, low-voltage ECG, increased septal thickness on echo with a "sparkling" texture), hepatomegaly, and a sensory and autonomic neuropathy.[1]

The differential — a monoclonal protein is not always myeloma

A monoclonal protein is not diagnostic of myeloma on its own — most monoclonal gammopathies are MGUS. The differential separates the plasma-cell and lymphoplasmacytic disorders, the mimics of bone lesions, and the mimics of hypercalcaemia and renal failure.[1][3]

[1]

Lytic bone lesions must be distinguished from metastatic carcinoma (breast, prostate, lung, kidney, thyroid — prostate and breast are usually mixed or sclerotic; renal and thyroid are classically lytic), osteoporotic compression fractures, brown tumours of hyperparathyroidism, and Paget disease (sclerotic, thickened cortex).[1]

Hypercalcaemia may alternatively reflect primary hyperparathyroidism (a high or inappropriately normal PTH), solid-tumour humoral hypercalcaemia (PTHrP), vitamin-D toxicity, or skeletal metastases — myeloma hypercalcaemia has a suppressed PTH and a paraprotein.[1]

The bedside round — and the high-ESR clue

The focused bedside examination has three jobs: detect the CRAB features, screen for amyloidosis, and exclude the oncological emergencies (cord compression, hyperviscosity).[1]

Run it in order: general (pallor, cachexia, bruising, dehydration or confusion from hypercalcaemia; document performance status); skeleton (bony tenderness over spine, skull, sternum, ribs, pelvis and long bones; spinal deformity from vertebral collapse); neurology (look hard for cord compression — motor weakness, a sensory level, sphincter disturbance — and for peripheral neuropathy); cardiorespiratory (anaemia, cardiac failure or restriction from amyloid); abdomen (hepatosplenomegaly suggests amyloidosis, Waldenström or overlap); the amyloidosis screen (macroglossia, periorbital purpura, the shoulder-pad sign); and the eyes and fundi (hyperviscosity retinopathy with "sausage-link" veins).[1]

Investigations — the must-not-miss set

The myeloma workup has four pillars: bloods and urine (anaemia, renal function, calcium, the paraprotein, prognostic markers), bone-marrow biopsy (the clonal plasma-cell burden and cytogenetics), imaging (the bone lesions), and the diagnostic and staging criteria.[1][3]

The paraprotein workup — do not omit any of these:[1]

• Serum protein electrophoresis (SPEP) with immunofixation — detects the sharp, narrow M-band and identifies the heavy- and light-chain type. A broad-based band is polyclonal, not myeloma.
• Serum free light chain (FLC) assay with kappa-to-lambda ratio — essential. A normal SPEP does not exclude light-chain or non-secretory myeloma; only the FLC assay detects these.
• Urine electrophoresis (UPEP) and immunofixation on a 24-hour collection — detects Bence Jones protein. A routine urine dipstick is negative in Bence Jones proteinuria because dipsticks detect albumin, not light chains — a classic exam point.[1]

Bone-marrow aspirate and trephine biopsy gives the clonal plasma-cell percentage (multinucleate, nucleolated cells with a perinuclear hof), the immunophenotype (CD138+, CD38+, aberrant CD56+, monoclonal light-chain restriction), and — critically — FISH cytogenetics for the high-risk lesions.[1]

Imaging:[1]

[1] [1]

Diagnostic criteria — IMWG 2014 (CRAB plus three biomarkers)

Symptomatic (active) multiple myeloma requires clonal marrow plasma cells at least 10 percent (or a biopsy-proven plasmacytoma) plus one or more myeloma-defining events attributable to the plasma-cell disorder.[3]

CRAB end-organ damage:[1]

• C — hyperCalcaemia — corrected calcium more than 0.25 mmol/L (1 mg/dL) above the upper limit of normal, or over 2.75 mmol/L (11 mg/dL).
• R — Renal insufficiency — creatinine clearance under 40 mL/min or serum creatinine over 177 micromol/L (2 mg/dL).
• A — Anaemia — haemoglobin more than 2 g/dL (20 g/L) below the lower limit of normal, or under 100 g/L.
• B — Bone lesions — one or more osteolytic lesions on whole-body CT, PET-CT or MRI.[3]

OR a biomarker of malignancy (a myeloma-defining event even without CRAB):[3]

• Serum involved-to-uninvolved free light chain ratio at least 100 (with the involved FLC at least 100 mg/L).
• More than one focal lesion on MRI (each at least 5 mm).
• Clonal marrow plasma cells at least 60 percent.[3]

[3]

Staging — the ISS and the Revised ISS (R-ISS)

The ISS uses serum beta-2 microglobulin and albumin alone.[4]

• ISS Stage I — beta-2 microglobulin under 3.5 mg/L AND albumin at least 35 g/L.
• ISS Stage II — neither stage I nor III.
• ISS Stage III — beta-2 microglobulin at least 5.5 mg/L.[1]

The Revised ISS (R-ISS) adds LDH and high-risk cytogenetics:[4]

[1]

The high-risk cytogenetic lesions in R-ISS are del(17p)/TP53, t(4;14) and t(14;16) (by FISH). A raised LDH is the third adverse factor.[2]

The first 24 hours — AKI and hypercalcaemia

Treat the presenting emergencies first, then start systemic anti-myeloma therapy (which itself treats the driver of the crisis).[1]

Hypercalcaemia: aggressive IV isotonic saline titrated to volume status, an IV bisphosphonate — zoledronic acid 4 mg as an infusion every 3 to 4 weeks is the schedule used in the MRC Myeloma IX trial — or denosumab 120 mg subcutaneously every 4 weeks (the dose used in the phase 3 myeloma bone-disease comparison against zoledronic acid), and treat the myeloma. Consider calcitonin for rapid but transient lowering in severe symptomatic disease.[7][8]

Cast nephropathy or AKI: the aim is to reduce the filtered light-chain load and remove the precipitant. Give aggressive IV hydration, strictly avoid NSAIDs and iodinated contrast, correct the hypercalcaemia, treat infection, and start bortezomib-based therapy promptly — bortezomib-based induction is usable in severe renal impairment including dialysis dependence: in a prospective series, 73 percent achieved a renal response and over half of the dialysis-dependent patients became dialysis-independent.[1][10]

Spinal cord compression: an oncological emergency — IV dexamethasone 10 to 16 mg immediately, urgent whole-spine MRI within 24 hours, and urgent clinical review for radiotherapy (radiosensitive disease) or surgical decompression (spinal instability, an unknown primary, or neurological deterioration despite steroids).[1]

Hyperviscosity syndrome: urgent plasmapheresis (plasma exchange) to remove the excess immunoglobulin, then systemic therapy.[1]

[1] [7] [10]

Induction — VRd and the transplant fork

Myeloma therapy is risk-adapted and transplant-status-driven. The disease remains incurable but highly treatable, managed as a chronic relapsing-remitting condition. Fit, younger patients get induction, then autologous stem-cell transplant, then maintenance; older or frail patients get continuous combination therapy. Every patient gets supportive care.[1][2][5]

The standard induction is VRd — bortezomib, lenalidomide, dexamethasone — given as 21-day cycles: in SWOG S0777, eight cycles of VRd improved median progression-free survival (43 versus 30 months) and median overall survival (75 versus 64 months) versus lenalidomide-dexamethasone alone.[6]

[1] [6] [11] [12]

Alternative inductions depend on cytogenetics, renal function and access: VTD (bortezomib plus thalidomide plus dexamethasone), KCD (carfilzomib plus cyclophosphamide plus dexamethasone), or Dara-VRd (adding daratumumab, supported by the GRIFFIN and CASSIOPEIA data). For high-risk cytogenetics, bortezomib-containing regimens are essential — bortezomib overcomes the adverse effect of t(4;14).[2][5]

Autologous SCT and maintenance

For fit patients (generally under 70 to 75 with good performance status, ECOG 0 to 1, without severe comorbidity — selected by physiological, not chronological, age), autologous stem-cell transplant after high-dose melphalan conditioning prolongs progression-free and overall survival. Mobilise peripheral-blood stem cells (cyclophosphamide plus G-CSF, plus plerixafor if needed), apherese at least 2 to 4 million CD34+ cells/kg, condition with high-dose melphalan 200 mg/m² IV over two days, and re-infuse the autologous cells; engraftment takes 10 to 14 days.[1]

Maintenance is lenalidomide 10 to 15 mg orally daily, days 1 to 21 of a 28-day cycle, until progression; for high-risk cytogenetics, bortezomib-based maintenance may be preferred.[1]

Transplant-ineligible patients get DRd — daratumumab plus lenalidomide plus dexamethasone — continuing until progression or unacceptable toxicity. In the MAIA trial, DRd reduced the risk of disease progression or death by 44 percent versus lenalidomide-dexamethasone alone (30-month progression-free survival 70.6 versus 55.6 percent), with deeper responses (complete response or better 47.6 versus 24.9 percent) but more grade 3-4 neutropenia and pneumonia.[9] Alternatives include VRd-lite, Dara-VMP (ALCYONE) and VMP alone.[1]

[9]

Relapsed and refractory myeloma

Myeloma relapses in virtually every patient. The armamentarium is deep, chosen by prior exposure, response, tolerance and access:[2]

[1]

Supportive care — every patient, every line

[1] [7] [8]

The subtypes that bite

• Smouldering (asymptomatic) myeloma — no CRAB and no biomarker by definition. Risk-stratify with the Spanish (PETHEMA) and Mayo models; the biomarkers (FLC ratio at least 100, more than one focal MRI lesion, marrow plasma cells at least 60 percent) automatically reclassify the patient as symptomatic. High-risk smouldering disease may be treated early with lenalidomide plus or minus dexamethasone.[3]
• Non-secretory and light-chain (Bence Jones) myeloma — no measurable intact M-band on SPEP; monitor with serum free light chains and imaging.[1]
• Solitary plasmacytoma of bone — radiotherapy with curative intent (40 Gy in 20 fractions); about half progress to myeloma within 10 years.[1]
• POEMS syndrome — lambda paraprotein, osteosclerotic (not lytic) lesion, raised VEGF; radiotherapy for a dominant lesion or lenalidomide-based therapy for disseminated disease.[1]
• AL amyloidosis — multi-organ involvement; diagnose with Congo-red staining (apple-green birefringence) of a fat-pad or marrow biopsy; treat with proteasome-inhibitor or daratumumab-based therapy.[1]
• Plasma-cell leukaemia — more than 2,000 circulating plasma cells per microlitre or 20 percent plasma cells on the blood film; aggressive, treated with VRd or Dara-VRd and ASCT in fit patients; prognosis poor.[1]

When it goes wrong — complications and the traps that cost marks

Disease complications: pathological fractures (vertebral collapse, long-bone fracture) and spinal cord compression, hypercalcaemic crisis, renal failure (cast nephropathy, amyloidosis, light-chain deposition disease), recurrent infection, hyperviscosity syndrome, AL amyloidosis, cytopenias, and extramedullary disease.[1]

Treatment complications — examiners test these by drug:[1]

[1]

The classic diagnostic pitfalls:[1]

• Missing a small IgD, IgE or light-chain myeloma by sending only a SPEP — always add serum free light chains.
• Urine dipstick is negative in Bence Jones proteinuria — use UPEP, not dipstick.
• Attributing renal failure or anaemia to "old age" in a 70-year-old — send a paraprotein screen.
• Performing a plain skeletal survey instead of whole-body low-dose CT.
• Forgetting FISH cytogenetics on the marrow.
• Giving iodinated contrast or NSAIDs to a patient with cast nephropathy.
• Forgetting aciclovir prophylaxis on bortezomib.
• Forgetting VTE prophylaxis with lenalidomide or thalidomide regimens.[1]

Prognosis and disposition

The Revised International Staging System (R-ISS) is the bedside prognostic tool:[4]

• Stage I — beta-2 microglobulin under 3.5 mg/L, albumin at least 35 g/L, normal LDH, no high-risk cytogenetics — median survival about 62 to 83 months.
• Stage II — intermediate.
• Stage III — beta-2 microglobulin at least 5.5 mg/L OR high-risk cytogenetics with high LDH — median survival about 29 months.[1]

Overall median survival is now 7 to 10 years, and over 10 years for standard-risk transplant-eligible patients who achieve a complete response. Adverse factors include high-risk cytogenetics (del(17p)/TP53, t(4;14), t(14;16), gain(1q)), a high LDH, renal failure at diagnosis, extramedullary disease, plasma-cell leukaemia, frailty, and a high R-ISS stage.[1][2]

Myeloma remains incurable but treatable. The depth of response (complete response, MRD-negativity) correlates with longer survival. Follow-up is by serial M-protein or free-light-chain monitoring every 1 to 3 months, imaging for new bone disease, surveillance for treatment toxicity, and vigilance for second primaries.[1]

Special populations

• Elderly and frail — dose-reduced regimens (VRd-lite, DRd, Dara-VMP), continuous therapy; ASCT selected by physiological, not chronological, age (a fit 75-year-old can be transplanted, a frail 60-year-old cannot). Use a geriatric assessment.[1]
• Renal impairment — bortezomib-based therapy is the backbone and is usable even in dialysis dependence; lenalidomide is renally cleared and must be dose-adjusted (the standard 25 mg starting dose drops to 10 mg with impaired kidney function — estimate renal function with Cockcroft-Gault); avoid NSAIDs and contrast; even dialysis-dependent patients can receive autologous transplant using reduced-dose melphalan with peritransplant dialysis support.[10][12][13]
• Resource-limited settings — thalidomide plus melphalan plus prednisolone (MPT) or VMP as lower-cost alternatives. Access, not biology, drives treatment choice in LMICs.[1]
• Pregnancy — extremely rare; avoid ionising radiation (use MRI); thalidomide and lenalidomide are absolutely contraindicated.[1]

The evidence and regional differences

IMWG 2014 (Rajkumar, Lancet Oncol) was a paradigm shift — adding myeloma-defining biomarkers (FLC ratio at least 100, more than one focal MRI lesion, marrow plasma cells at least 60 percent) so that high-risk patients can be treated before end-organ damage develops, moving from "treat only when CRAB" to "treat when the biology says it will cause harm".[3]

[1] [1]

Controversies the exam may probe: early treatment of high-risk smouldering myeloma versus watchful waiting; continuous versus fixed-duration therapy; MRD-guided treatment discontinuation; the role of tandem ASCT in high-risk disease; the duration of maintenance; and the place of bispecifics and CAR-T in earlier lines.[1]

The mantra, and the mnemonics

[1]

The mantra: CRAB plus a biomarker makes myeloma; bortezomib saves the kidney; the dipstick is negative in Bence Jones proteinuria; FISH, not karyotyping, finds the high-risk lesions.[1][3]

Ward-round test — three stems, thirty seconds each

Stem 1 — the man from the top of the topic (answer)

A 69-year-old with back pain, constipation, confusion, calcium 3.1 mmol/L, creatinine 220 micromol/L, Hb 88 g/L, ESR 120 mm/h with rouleaux, and punched-out skull lesions. What is the diagnosis, the diagnostic bundle, and the first 24-hour plan? Model: This is multiple myeloma with the full CRAB tetrad (hyperCalcaemia, Renal, Anaemia, Bone). Send the diagnostic bundle — SPEP plus immunofixation, serum free light chains, urine Bence Jones, beta-2 microglobulin, LDH, albumin, a FISH-ready marrow biopsy, and whole-body low-dose CT. The first 24 hours: aggressive IV isotonic saline (3 to 6 L, monitor volume), stop NSAIDs and iodinated contrast, correct the hypercalcaemia with zoledronic acid 4 mg IV, and start bortezomib-based therapy promptly — bortezomib is hepatically cleared and safe in renal failure, and it is the fastest way to reduce the light-chain load damaging the kidney. Confirm the diagnosis with marrow plasma cells at least 10 percent plus a myeloma-defining event, and stage with the R-ISS.[1][3]

Stem 2 — the negative dipstick that is not negative (answer)

A 72-year-old with fatigue and ankle oedema has a urine dipstick negative for protein but a 24-hour urine collection of 3 g of protein. SPEP shows a small IgG lambda band. What is happening, and what single test confirms it? Model: This is light-chain (Bence Jones) proteinuria — the dipstick is negative because dipsticks detect albumin, not free light chains. The 24-hour urine (or UPEP with immunofixation) detects the monoclonal free light chains clogging the kidney. Confirm with a serum free light chain assay (which will show a deranged kappa-to-lambda ratio, typically at least 100 in symptomatic myeloma) and a marrow biopsy with FISH. The lesson: a normal SPEP and a negative dipstick do not exclude myeloma — always add serum free light chains.[1][3]

Stem 3 — the new paraprotein that pan-reacts the blood bank (answer)

A 68-year-old on daratumumab for myeloma needs an urgent transfusion. The transfusion laboratory reports that the antibody panel pan-reacts and they cannot exclude an alloantibody. Why, and what do you do? Model: Daratumumab is an anti-CD38 monoclonal antibody, and CD38 is expressed on red cells — so the antibody coats the reagent red cells and pan-reacts in the indirect antiglobulin test, masking any underlying clinically significant alloantibody. Notify the transfusion laboratory before any blood is needed (type-and-screen before the first dose), and the lab can resolve the interference with a DTT-treated panel or by adding anti-idiotype antibody (daratumumab is DTT-sensitive; true alloantibodies are not). This is a classic modern myeloma trap and the reason every daratumumab patient needs a transfusion-lab flag.[1]

References

1. [1]Kumar SK, Rajkumar V, Kyle RA, et al. Multiple myeloma Nat Rev Dis Primers, 2017.PMID 28726797
2. [2]Sonneveld P, Avet-Loiseau H, Lonial S, et al. Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group Blood, 2016.PMID 27002115
3. [3]Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma Lancet Oncol, 2014.PMID 25439696
4. [4]Palumbo A, Avet-Loiseau H, Oliva S, et al. Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group J Clin Oncol, 2015.PMID 26240224
5. [5]Moreau P, Attal M, Hulin C, et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study Lancet, 2019.PMID 31171419
6. [6]Durie BGM, Hoering A, Abidi MH, et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial Lancet, 2017.PMID 28017406
7. [7]Morgan GJ, Davies FE, Gregory WM, et al. First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial Lancet, 2010.PMID 21131037
8. [8]Raje N, Terpos E, Willenbacher W, et al. Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: an international, double-blind, double-dummy, randomised, controlled, phase 3 study Lancet Oncol, 2018.PMID 29429912
9. [9]Facon T, Kumar S, Plesner T, et al. Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma N Engl J Med, 2019.PMID 31141632
10. [10]Sharma R, Jain A, Jandial A, et al. Lack of Renal Recovery Predicts Poor Survival in Patients of Multiple Myeloma With Renal Impairment Clin Lymphoma Myeloma Leuk, 2022.PMID 35610119
11. [11]Moreau P, Pylypenko H, Grosicki S, et al. Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study Lancet Oncol, 2011.PMID 21507715
12. [12]Salama E, Lam S, Gonsalves WI, et al. Estimation of Kidney Function in Patients With Multiple Myeloma: Implications for Lenalidomide Dosing Ann Pharmacother, 2023.PMID 35511200
13. [13]Singh S, Sharma R, Singh J, et al. Autologous stem cell transplantation can potentially reverse dialysis dependence in patients with myeloma: Report of two cases and practical considerations Natl Med J India, 2024.PMID 39399996