Multiple Myeloma

Name: Multiple Myeloma: Mini Review for Clinicians, Algorithms & Cases
Creator: Dr. Haritha Chiramana
License: https://creativecommons.org/licenses/by-nc-nd/4.0/

Haematological cancers, part 6 · Multiple myeloma, MGUS, smoldering myeloma and solitary plasmacytoma · Diagnosis and risk · Quadruplet induction, transplant and maintenance · BCMA-directed therapy at relapse · Bone, kidney and infection care · Key points for clinicians · Last updated 17 October 2026

For health professionals. This section uses clinical terms and is general education for doctors, nurses and students, not advice for an individual patient. Patients and families: please read our patient guides instead, Cancer Myth Busters · Understanding your cancer report · Living through cancer treatment, or speak with your own doctor.

Who this page is for, and where to start

Printable PDFs for this moduleMini reviews, slides, algorithms, quick references and the MCQ booklet are on the Printable Teaching Resources page. No PDF downloads are kept on this page.

Printable Teaching Resources →

For your patientsPlain-language Telugu–English answers for patients and families: the Multiple myeloma Myth Busters (20 myths), symptoms and warning signs and the Telugu handouts.

Open the multiple myeloma myths →

SurgeonsScreening and workup (03), local therapy with surgery types (05), algorithms (07), cases (11)

Physicians & oncologistsBiomarkers (04), systemic therapy (06), algorithms (07), survivorship (08), cases (11)

Postgraduate residentsOncology and other specialities: case vignettes (11), landmark trials (09) and 0 cited trials (12) for exams and journal clubs

Medical studentsAt a glance (01), presentation and common traps (02), the figures, and follow-up (08)

Prepared and reviewed by Dr. Haritha Chiramana, MD, DM, Senior Medical Oncologist & Hemato-Oncologist, C.R. Reddy Cancer Center, Nellore, Andhra Pradesh, India. She teaches oncology to postgraduates and medical students; colleges and departments may write to info@drharitha.co.in for teaching sessions. Printable Teaching Resources and how to cite → Phone 0861 232 5344 · WhatsApp +91 79896 42272.

01 At a glance

Myeloma is a cancer of plasma cells in the marrow, about 1–2% of all cancers and one in six haematological cancers. Almost every case is preceded by MGUS, a silent clone found in over 3% of people above 50 (Landgren 2009^[1]).
Four clinical pictures, one biology: MGUS (watch), smoldering myeloma (watch, or treat if high risk), active myeloma (treat now) and solitary plasmacytoma (radiotherapy). The line between them is drawn by M protein size, marrow plasma cells, imaging and organ damage.
Active myeloma = clonal plasma cells plus a myeloma-defining event: CRAB (calcium, renal impairment, anaemia, bone lesions) or a SLiM biomarker (≥60% marrow plasma cells, light-chain ratio ≥100, more than one focal MRI lesion) (IMWG 2014^[2]).
Screen with three blood tests, not one: serum protein electrophoresis with immunofixation and serum free light chains. A normal SPEP or a normal urine dipstick does not exclude light-chain myeloma. Image with low-dose whole-body CT, PET-CT or MRI, not X-rays or bone scans.
Risk is biological: del(17p)/TP53, a high-risk translocation with chromosome 1 changes, or a high beta-2 microglobulin with normal kidneys mark the 20% who do worst (IMS/IMWG 2025^[3]).
First-line treatment is a four-drug combination for most (an anti-CD38 antibody with bortezomib, lenalidomide and dexamethasone), autologous transplant for the fit, then lenalidomide-based maintenance. Where drugs are scarce, a bortezomib triplet (VTd or VCd) with transplant remains effective.
Relapse is expected and treatable: BCMA-directed CAR-T cells, bispecific antibodies and belantamab now improve survival from first relapse (CARTITUDE-4^[4], MajesTEC-3^[5]).
Supportive care saves lives: bone-protecting drugs, early antibiotics and antivirals, vaccines, clot prevention with IMiDs, fluids and fast treatment for kidney injury, and emergency MRI for back pain with weakness.
India: patients are often younger (median 57 years in an Eastern Indian series) and present later, after months of "backache" or "kidney disease"; few receive a transplant because of cost; generic bortezomib and lenalidomide have widened access.

Figure 1. The spectrum at a glance (IMWG criteria, Rajkumar 2014; UpToDate MGUS, smoldering myeloma, myeloma diagnosis and plasmacytoma reviews).

02 Clinical presentation, common traps & causes

Figure 2. Presenting features (Kyle 2003, 1027 Mayo patients; UpToDate myeloma diagnosis review). Earlier testing now finds more patients before bone damage.

Who gets it, and why

Myeloma: median age 65–74 in Western series; only 10% are under 50 and 2% under 40; men slightly more than women (1.4:1); two to three times more common in people of African descent (Kyle 2003^[6]).
Causes: unknown in most. Risk rises with age and body mass index; radiation, benzene and some pesticides are associated. A first-degree relative with myeloma raises the risk about 3.7-fold, but familial clusters are rare and testing relatives is not routine.
MGUS: 3.2% of people at ≥50, 5.3% at ≥70 and 7.5% at ≥85 years in Olmsted County; more in men (Kyle 2006^[7]). Non-IgM MGUS (about 80%) leads to myeloma or AL amyloidosis; IgM MGUS (about 15%) leads to Waldenström or lymphoma; light-chain MGUS to light-chain myeloma or AL.
Smoldering myeloma: about 10% progress each year for the first 5 years, 3% a year for the next 5, then 1–2% a year; median time to progression 4.8 years (Kyle 2007^[8]).
Solitary plasmacytoma: about 5% (bone) and 3% (soft tissue) of plasma cell disorders; soft-tissue tumours sit in the nose, sinuses and nasopharynx in 45–80%, so they reach ENT surgeons first.
How myeloma presents: anaemia (73%), central bone pain worse on movement (58%), raised creatinine (48%; >2 mg/dL in about 20%), fatigue, high calcium (28%) and weight loss (24%). Height loss from vertebral collapse; recurrent pneumococcal infections; occasionally a purplish skin or soft-tissue mass.
India: in 696 patients at a North Indian centre (median age 66, 65% men), 5-year survival was 83%, worse with weight loss, kidney dysfunction and anaemia at diagnosis (Yanamandra 2021^[9]). In an Eastern Indian series the median age was 57 and patients with del(17p) were younger (Jha 2023^[10]).

Common traps

Months of painkillers for "lumbar spondylosis" or "osteoporosis". Back pain in an adult with anaemia, a high ESR or a high total protein needs SPEP, free light chains and imaging. NSAIDs given for that pain then damage the kidney.
"Chronic kidney disease" in a 55-year-old with no diabetes or hypertension. Unexplained kidney injury, especially with anaemia or bland urine with little albumin, needs serum free light chains.
A normal SPEP or negative urine dipstick read as "no myeloma". Light-chain myeloma (about 15–20%) may show no spike, and the dipstick does not detect Bence Jones protein.
Anaemia treated with iron and B12 for months. Normocytic anaemia with rouleaux, high ESR or high globulins: test for a monoclonal protein.
A vertebral collapse fixed without a biopsy. A solitary bone lesion should never be fixed without tissue; a plasmacytoma or a metastasis changes everything.
An incidental small M protein turned into a cancer label. Most MGUS never progresses; frightening patients, or repeating marrow tests in low-risk MGUS, does harm.
A nasal "polyp" with epistaxis sent for routine polypectomy. Extramedullary plasmacytoma needs immunohistochemistry (CD138, light-chain restriction) and full staging.

03 Diagnosis, workup & staging essentials

Making the diagnosis

Initial tests for any suspected plasma cell disorder: CBC, calcium, creatinine, SPEP with immunofixation, serum free light chains and quantitative immunoglobulins. If a protein is found or the ratio is abnormal: 24-hour urine electrophoresis and immunofixation (baseline M protein and a check for nephrotic albuminuria).
Marrow aspirate and biopsy: clonal plasma cells by CD138 staining or flow cytometry (κ/λ restriction); FISH on CD138-selected cells. Involvement can be patchy, so a low count with lytic lesions needs a lesion biopsy or a second marrow site.
Imaging: whole-body low-dose CT (quick, cheap, sensitive) for new myeloma; whole-body or spine-pelvis MRI for suspected smoldering myeloma or solitary plasmacytoma; PET-CT for suspected extramedullary disease; MRI for cord compression (Hillengass 2019^[11]). Skeletal X-ray surveys and bone scans miss lesions.
Myeloma: clonal marrow plasma cells ≥10% or a biopsy-proven plasmacytoma, plus CRAB attributable to the clone (calcium >11 mg/dL, creatinine >2 mg/dL or clearance <40 mL/min, haemoglobin <10 g/dL or >2 g/dL below normal, one or more lytic lesions on CT, PET-CT or X-ray) or a SLiM biomarker (IMWG 2014^[2]).
Smoldering myeloma: serum M protein ≥3 g/dL or urine ≥500 mg/24 h and/or 10–59% marrow plasma cells, with no myeloma-defining event and no amyloidosis. MGUS: M protein <3 g/dL, <10% marrow plasma cells (if done), no end-organ damage; light-chain MGUS if only light chains are abnormal (ratio <100).
Solitary plasmacytoma: one biopsy-proven tumour of bone or soft tissue, no other lesions on MRI or PET-CT, no CRAB, and no clonal marrow plasma cells (if <10% are present: "with minimal marrow involvement"; ≥10% = myeloma) (Caers 2018^[12]).

Figure 3. Monoclonal protein tests (UpToDate laboratory methods for monoclonal proteins review). Schematic drawing, not to scale.

Figure 4. Work-up of a suspected plasma cell disorder (IMWG criteria, Rajkumar 2014; IMWG imaging consensus, Hillengass 2019; UpToDate MGUS and myeloma diagnosis reviews).

Not myeloma: the differentials to exclude

AL amyloidosis: often <10% marrow plasma cells and a small λ protein, with nephrotic albuminuria, heart failure with thick walls, neuropathy, macroglossia or periorbital bruising: tissue biopsy with Congo red (separate module later).
Waldenström macroglobulinaemia: an IgM protein (seen in <1% of myeloma), lymphoplasmacytic cells (CD19, CD20), MYD88 L265P in >90%; IgM myeloma needs lytic lesions or t(11;14) (indolent B-cell module).
POEMS syndrome: polyneuropathy, sclerotic bone lesions, organomegaly, endocrinopathy, skin changes and a small λ protein; high VEGF.
Plasma cell leukaemia: ≥5% clonal plasma cells on the blood smear; aggressive, treated in specialised centres.
Metastatic carcinoma with an unrelated MGUS: lytic lesions plus a small protein are not always myeloma; biopsy the lesion. Polyclonal increase (infection, liver disease, autoimmunity): a broad band, not a spike.
MGRS: kidney damage from a small, non-malignant clone (deposition disease, cryoglobulinaemia, light-chain tubulopathy); diagnosed by kidney biopsy and treated against the clone.

Before treatment

Area	What to do	Why
Disease burden	SPEP, immunofixation, free light chains, 24-h urine; marrow with FISH (± NGS for TP53)	Baseline for response; IMS/IMWG risk
Staging	Albumin, beta-2 microglobulin, LDH	R-ISS; high-risk B2M (≥5.5 mg/L with normal creatinine)
Bones	Low-dose whole-body CT (PET-CT or MRI as needed); DXA if no lesions	Bone drug, RT, fixation, cord risk
Kidneys	Creatinine, urine albumin, 24-h urine; biopsy if albuminuria or light chains not very high	Cast nephropathy vs AL/MIDD/MGRS; drug choice
Infection and blood bank	HBV, HCV, HIV; varicella status; type and screen before daratumumab	Prophylaxis; anti-CD38 interferes with cross-matching
Fitness	Performance status, comorbidity, frailty; heart and lung tests if transplant considered	Transplant eligibility; dose adjustment
Teeth	Dental examination before a bone drug	Jaw osteonecrosis prevention

04 Biology and biomarkers that change treatment

Biology in brief

Two starting routes: about half of MGUS begins with an IgH translocation at 14q32 (t(11;14) in about 25%, t(4;14) 15%, t(14;16) 5%, t(6;14) 3%, t(14;20) 2%) and most of the rest with trisomies of odd-numbered chromosomes (hyperdiploid). These early events happen decades before diagnosis.
Progression to myeloma adds secondary hits: MYC rearrangement, 1q gain, 1p and 17p loss, TP53 and RAS/MAPK mutations, NF-κB activation and APOBEC mutagenesis, helped by a supportive marrow niche.
Bone destruction comes from osteoclast activation (high RANKL, low osteoprotegerin) with suppressed osteoblasts (DKK1): lesions are purely lytic and do not light up on bone scans; they rarely heal fully.

Figure 5. Risk stratification (IMS/IMWG, Avet-Loiseau 2025; R-ISS, Palumbo 2015; UpToDate staging review). FISH: fluorescence in situ hybridisation.

Marker or feature	What it tells you	What it changes
del(17p) (≥20% of cells) or TP53 mutation	High risk (IMS/IMWG 2025)	Quadruplet induction, early HCT, two-drug maintenance; trials
t(4;14), t(14;16) or t(14;20) with 1q+ and/or del(1p32)	High risk	As above; a proteasome inhibitor in maintenance
1q gain or amplification; del(1p32)	Adverse; combined they define high risk	As above
B2M ≥5.5 mg/L with creatinine <1.2 mg/dL	High risk (tumour burden)	As above
t(11;14)	Standard risk; BCL-2 dependence	Venetoclax option at relapse (off-label)
R-ISS I / II / III	5-year OS 82% / 62% / 40% (Palumbo 2015^[13])	Prognosis; trial comparison
Circulating plasma cells; plasmablastic morphology; extramedullary disease	Aggressive biology	Fast, intensive therapy; ≥5% on smear = plasma cell leukaemia
Frailty and comorbidity	Tolerance	Dose-reduced, dexamethasone-sparing regimens

Testing needed: FISH for 17p, 1p, 1q and an IGH break-apart with reflex partners; NGS for TP53 mutation (reasonable to reserve it for cases without del(17p) when resources are limited). Older systems (R-ISS, R2-ISS^[14]) remain useful for comparing trials.

05 Local therapy: radiotherapy, surgery & procedures

Radiotherapy for solitary plasmacytoma

Figure 6. Solitary plasmacytoma (Caers 2018; ILROG, Tsang 2018; Paiva 2014; UpToDate SPB and SEP reviews).

Bone (SPB): involved-site RT 35–50 Gy over about 4 weeks, lower end for tumours <5 cm, higher for larger; field covers the lesion with a margin of at least 2 cm and one uninvolved vertebra above and below for spinal lesions; give RT even after complete excision. Local control exceeds 80–90% (ILROG 2018^[15]).
Soft tissue (SEP): after incomplete excision or biopsy alone, RT 40–50 Gy (doses below 40 Gy did worse); after complete excision, observation is reasonable (some give RT). Fewer than 7% recur locally; 10–15% develop myeloma (Ozsahin 2006^[16]).
No adjuvant chemotherapy and no routine bisphosphonate for either; the role of systemic therapy for minimal marrow involvement is being studied.

Palliative radiotherapy in myeloma

Indications: uncontrolled bone pain, cord or root compression, impending or actual fracture, and after fixation of long bones. Up to 40% of patients need RT at some point.
Low doses work: no clear dose-response; 10–12 Gy often controls pain, and 8 Gy in one fraction gave pain relief similar to 30 Gy in 10 fractions (74% vs 85%; Rudzianskiene 2017^[17]). For cord compression, longer fractionation gives better motor recovery.
Keep fields small to protect marrow reserve and future stem cell collection; the whole fixation hardware need not be covered. Use RT with proteasome inhibitors cautiously (more cytopenias).

Surgery and procedures

Cord compression is an emergency: back pain almost always comes first; MRI of the whole spine within 24 hours (CT myelography if MRI impossible), dexamethasone, then RT; fast systemic therapy may be enough with minimal deficit; surgery if the deficit progresses, the spine is unstable or retropulsed bone compresses the cord.
Long bones: a lesion destroying ≥50% of cortical thickness, or a high Mirels score, needs prophylactic fixation by an orthopaedic oncologist; radiograph the whole bone first.
Vertebral compression fractures: kyphoplasty or vertebroplasty relieve pain and improve function (CAFE^[18]); assess stability (SINS) first.
Diagnosis: biopsy any solitary bone lesion before fixation; complete excision of a soft-tissue plasmacytoma can be curative.

06 Systemic therapy: indications & options

MGUS: watch, do not treat

Figure 7. MGUS risk and follow-up (Rajkumar 2005; Kyle 2006 and 2018; UpToDate MGUS diagnosis and clinical course reviews).

Risk model: M protein ≥1.5 g/dL, non-IgG type and an abnormal free light-chain ratio; 20-year progression 5%, 21%, 37% and 58% with 0, 1, 2 and 3 factors (Rajkumar 2005^[19], Kyle 2018^[20]).
Follow-up: repeat tests at 6 months; low risk then every 2–3 years; others yearly with history and examination. Marrow and imaging can be skipped in low-risk MGUS without CRAB features.
Watch for clinical significance: kidney damage (MGRS), neuropathy, skin disease or bleeding caused by the protein itself needs clone-directed treatment even without cancer. Bone drugs only for osteoporosis.

Smoldering myeloma

Figure 8. Smoldering myeloma (Kyle 2007; Lakshman 2018; AQUILA, Dimopoulos 2025; UpToDate smoldering myeloma review).

Risk: 20/2/20 (marrow plasma cells >20%, M protein >2 g/dL, light-chain ratio >20); two or three factors = high risk (Lakshman 2018^[21], IMWG 2020^[22]). MRI at baseline; repeat testing 2–3 months after diagnosis, then every 3–4 months.
Low and intermediate risk: observation; treatment has not been shown to improve outcomes.
High risk: early, time-limited treatment rather than observation. AQUILA (390 patients): daratumumab for up to 3 years vs monitoring, 5-year PFS 63% vs 41% and OS 93% vs 87%, benefit clearest in 20/2/20 high risk (AQUILA^[23]). Alternatives: lenalidomide for 2 years (E3A06^[24]: 2-year PFS 93% vs 76%) or lenalidomide-dexamethasone (QuiRedex^[25]: OS benefit). Full myeloma regimens only in trials.

Active myeloma: first-line treatment

Figure 9. First-line pathways (UpToDate initial treatment, HCT, overview and resource-limited settings reviews). D = daratumumab; Isa = isatuximab; V = bortezomib; R = lenalidomide; T = thalidomide; C = cyclophosphamide; d = dexamethasone; MP = melphalan-prednisone.

Start promptly: untreated symptomatic myeloma has a life expectancy under a year. Goals: reverse organ damage, deep and durable response, quality of life.
Quadruplets for most: in transplant-eligible patients D-VRd beat VRd (PERSEUS, 709 patients: MRD negativity 75% vs 48%, 48-month PFS 84% vs 68%; PERSEUS^[26]); Isa-VRd deepened responses (GMMG-HD7^[27]). In transplant-ineligible or deferred patients: CEPHEUS (D-VRd, 54-month PFS 68% vs 50%; CEPHEUS^[28]) and IMROZ (Isa-VRd, 5-year PFS 63% vs 45%; IMROZ^[29]).
Triplets remain good options: VRd improved OS over Rd (S0777^[30]); DRd improved OS over Rd in older patients (MAIA, 5-year OS 66% vs 53%; MAIA^[31]), suits pre-existing neuropathy and can be given dexamethasone-sparing to the frail; VCd when lenalidomide is risky (kidney injury, clots).
Autologous transplant: induction 3–6 cycles, stem cell collection (G-CSF; plerixafor if poor mobilisation), then high-dose melphalan. Early HCT lengthened PFS (IFM 2009: 50 vs 36 months; DETERMINATION: 68 vs 46 months) without OS difference (IFM 2009^[32], DETERMINATION^[33]). Prefer early HCT for high risk; eligibility depends on fitness, not age; collect for two transplants if under 65.
Maintenance: lenalidomide after HCT or induction delays progression (Myeloma XI^[34]). Two years appear as good as indefinite with less toxicity (ENDURANCE: 7-year OS 69% in both; Kumar 2026^[35]). Add an anti-CD38 antibody if MRD-positive; high risk: lenalidomide plus bortezomib (or carfilzomib or anti-CD38) until progression.
Limited resources: VTd or VCd (VTd gave more responses than VCd before HCT; IFM2013-04^[36]), then transplant if possible and thalidomide or lenalidomide maintenance; without bortezomib, CTd or MPT (no melphalan before stem cell collection). Thalidomide maintenance prolongs remission but not survival (Ludwig 2010^[37]).
Practical rules: subcutaneous, weekly bortezomib (less neuropathy); weekly rather than more frequent dexamethasone; subcutaneous daratumumab or isatuximab; dose-adjust lenalidomide for kidney function; second cancers rise with lenalidomide after HCT.

Figure 10. Early vs delayed HCT (IFM 2009, Attal 2017; DETERMINATION, Richardson 2022; UpToDate HCT review).

Relapsed myeloma

Figure 11. Relapsed myeloma (UpToDate relapsed disease and administration reviews). D = daratumumab; P = pomalidomide; K = carfilzomib; V = bortezomib; Isa = isatuximab; d = dexamethasone.

Assess first: drug sensitivity (refractory = progression within 60 days of a drug), FISH, organ function, infection risk and eligibility for CAR-T or a second HCT; refer early to a centre with cellular therapy.
First relapse: BCMA-directed therapy for most. Cilta-cel vs DPd/PVd in lenalidomide-refractory disease: 30-month PFS 59% vs 26%, OS 76% vs 64% (CARTITUDE-4^[4]). Teclistamab plus daratumumab vs DPd/DVd: 36-month PFS 83% vs 30%, OS 83% vs 65% (MajesTEC-3^[5]). BVd vs DVd: median PFS 37 vs 13 months, OS benefit, eye toxicity (DREAMM-7^[38]; BPd in DREAMM-8^[39]).
Triplets of unused classes (DPd, DKd, KPd, PVd, IsaKd, IRd) remain right for the frail, the infection-prone and those without access; a second HCT is possible with stored cells and a long first remission.
Later relapse: BCMA if not yet used (ide-cel improved PFS: KarMMa-3^[40]; bispecifics: MajesTEC-1^[41]); after BCMA, talquetamab (GPRC5D; MonumenTAL-1^[42]), selinexor, alkylators, venetoclax only for t(11;14); trials.

Supportive care: bone, kidney, infection, clots

Figure 12. Bone disease (Myeloma IX, Morgan 2010; Raje 2018; Rudzianskiene 2017; UpToDate osteoclast inhibitor, fracture, cord compression and overview reviews).

Osteoclast inhibitors: for lytic lesions or osteopenia (many guidelines: all patients needing treatment). Zoledronic acid improved OS over clodronate (Myeloma IX: median 52 vs 46 months; Myeloma IX^[43]); denosumab matched zoledronic acid with less kidney toxicity but more hypocalcaemia (Raje 2018^[44]). Creatinine clearance >30: zoledronic acid; ≤30: denosumab. Monthly for at least 2 years; dental clearance first; calcium and vitamin D; never stop denosumab without a bisphosphonate dose.
Hypercalcaemia: fluids, glucocorticoids, zoledronic acid (preferred over pamidronate; denosumab if refractory or kidney failure); check ionised calcium if high calcium without symptoms (a protein can bind calcium). Hyperviscosity (rare in myeloma): plasma exchange if symptomatic.

Figure 13. Kidney disease (MYRE, Bridoux 2017; UpToDate kidney disease etiology/evaluation and treatment reviews). ARB: angiotensin receptor blocker.

Cast nephropathy: start bortezomib, dexamethasone ± anti-CD38 at once; fluids for about 3 L of urine a day; stop NSAIDs, ACE inhibitors, ARBs and diuretics; correct calcium; dialysis for the usual indications, not to remove light chains. Plasma exchange or high cut-off dialysis is debated (MYRE^[45]).

Figure 14. Supportive care (TEAMM, Drayson 2019; SAVED, Li 2019; IMPEDE VTE, Sanfilippo 2019; UpToDate infections and VTE reviews).

Infection is a leading cause of death, highest in the first 3 months. Levofloxacin for the first 12 weeks reduced fever or death (19% vs 27%; TEAMM^[46]); aciclovir or valaciclovir with proteasome inhibitors and anti-CD38 antibodies; pneumococcal, influenza and recombinant zoster vaccines; PJP prophylaxis and IVIG with T-cell-engaging therapies.
Thrombosis with IMiDs: SAVED ≥2 (SAVED^[47]) or IMPEDE VTE ≥8 (IMPEDE VTE^[48]) = high risk → LMWH, a DOAC or warfarin; otherwise aspirin. Single-agent IMiD maintenance: aspirin.

India now (October 2026)

Indian data are web-verified: a North Indian series of 696 patients (median age 66, 5-year OS 83%; Yanamandra 2021), an Eastern Indian FISH series (median age 57; Jha 2023) and a 2016 expert panel noting that most patients pay themselves, few undergo transplant because of cost and stigma, and generic bortezomib and lenalidomide have widened access.
Availability and cost in India of daratumumab and isatuximab, carfilzomib, pomalidomide, belantamab, BCMA CAR-T cells, teclistamab and talquetamab, denosumab, free light chain assays, FISH/NGS and PET-CT, and access to autologous transplant, to be confirmed by the treating team.

Quick reference (also as a printable PDF on the Printable Teaching Resources page)

Table A. Diagnosis and staging tests and what they change

Test	When	What it changes	Pitfalls
SPEP + serum immunofixation	Every suspected plasma cell disorder	Size and type of M protein; MGUS vs SMM threshold (3 g/dL)	SPEP misses small or light-chain-only proteins
Serum free light chains (κ, λ, ratio)	Screening, light-chain myeloma, follow-up	Ratio ≥100 (involved ≥100 mg/L) = myeloma; MGUS risk	Ratio rises in kidney disease; use one manufacturer for follow-up
24-h urine electrophoresis + immunofixation	Protein found or ratio abnormal; baseline	Bence Jones protein; nephrotic albuminuria (AL, deposition disease)	Urine dipstick does not detect light chains
CBC, calcium, creatinine, albumin, LDH, B2M	Every case	CRAB; R-ISS; high-risk (B2M ≥5.5 with normal creatinine)	Check ionised calcium if high calcium without symptoms
Marrow aspirate + biopsy (CD138 or flow); FISH ± NGS	All except low-risk MGUS	≥10% clonal cells; 20/2/20; IMS/IMWG risk	Focal disease: a low count does not exclude myeloma
Whole-body low-dose CT (or PET-CT, MRI)	Every non-IgM protein except low-risk MGUS	Lytic lesions = myeloma; PET for extramedullary disease	Bone scans miss lytic lesions; X-rays are insensitive
Whole-body or spine-pelvis MRI	Suspected SMM or solitary plasmacytoma	>1 focal lesion = myeloma; rules out more lesions	Equivocal lesions: repeat in 3–6 months
Kidney biopsy	Albuminuria, or kidney injury without very high light chains	Cast nephropathy vs AL, deposition disease, MGRS	Correct bleeding risk first
HBV, HCV, HIV; echocardiogram, pulmonary function	Before anti-CD38, HCT or CAR-T	Antiviral prophylaxis; transplant fitness	Daratumumab interferes with blood-bank cross-matching

Table B. Treatment by setting

Setting	Standard choice	Key evidence	Notes
MGUS, low risk	Observe; tests at 6 months, then every 2–3 years	Rajkumar 2005^[19]	Bone drug only for osteoporosis
MGUS, other	Observe; yearly tests	Kyle 2018^[20]	Report new symptoms at once
SMM, low or intermediate risk	Observe closely	Lakshman 2018^[21]	MRI to exclude focal lesions
SMM, high risk (20/2/20)	Daratumumab for up to 3 years (or lenalidomide ± dexamethasone); trial	AQUILA^[23]	OS 93% vs 87% at 5 years
Solitary plasmacytoma of bone	RT 35–50 Gy; observe	ILROG 2018^[15]	RT even after complete excision
Extramedullary plasmacytoma	Incomplete excision: RT 40–50 Gy; complete: observe	Ozsahin 2006^[16]	Doses <40 Gy did worse
Myeloma, transplant eligible	D-VRd or Isa-VRd × 3–6 → collect → HCT → maintenance	PERSEUS^[26], GMMG-HD7^[27]	High risk: early HCT; two-drug maintenance
Myeloma, not transplant eligible	D-VRd or Isa-VRd; DRd or VRd if frail; then maintenance	CEPHEUS^[28], IMROZ^[29], MAIA^[31]	Frail: dose-reduced, dexamethasone-sparing
Limited resources	VTd or VCd (VRd if possible); CTd or MPT without bortezomib	IFM2013-04^[36]	Thalidomide maintenance after HCT
Maintenance, standard risk	Lenalidomide ~2 years (± anti-CD38)	ENDURANCE^[35]	Indefinite: same OS, more toxicity
First relapse	BCMA-directed (cilta-cel, teclistamab + daratumumab, BVd) or a triplet of unused classes	CARTITUDE-4^[4], MajesTEC-3^[5]	Triplet if infection-prone or no access
Later relapse	BCMA if unused; talquetamab; selinexor; venetoclax for t(11;14)	MonumenTAL-1^[42]	Trials encouraged

Table C. Treatment options: evidence and best fit

Option	Best for	Evidence	Watch for
D-VRd (daratumumab + VRd)	Fit patients, standard or high risk, ± HCT	PERSEUS^[26]: 48-month PFS 84% vs 68%; CEPHEUS^[28]: 54-month 68% vs 50%	Cytopenias, infections; plerixafor more often
Isa-VRd	As D-VRd	IMROZ^[29]: 5-year PFS 63% vs 45%; GMMG-HD7^[27]	Infusion reactions, infections
VRd	When a quadruplet is not possible	S0777^[30]: median OS NR vs 69 months vs Rd	Neuropathy (use subcutaneous, weekly)
DRd	Older, frail, pre-existing neuropathy	MAIA^[31]: 5-year OS 66% vs 53%	Neutropenia, pneumonia
VCd / VTd	Kidney injury, clot risk, limited resources	IFM2013-04^[36]: VTd more responses	Thalidomide: neuropathy, clots, constipation
Autologous HCT	Fit patients (age is not a bar)	DETERMINATION^[33]: PFS 68 vs 46 months; OS same	Mucositis, infection; second myeloid cancers
Lenalidomide maintenance	After HCT or induction	Myeloma XI^[34]	Second cancers, cytopenias, diarrhoea
Cilta-cel (BCMA CAR-T)	Lenalidomide-refractory, 1–3 prior lines	CARTITUDE-4^[4]: 30-month OS 76% vs 64%	CRS, ICANS, delayed neurotoxicity, cytopenias
Teclistamab + daratumumab	1–3 prior lines, not anti-CD38-refractory	MajesTEC-3^[5]: 36-month OS 83% vs 65%	CRS, infections (IVIG, prophylaxis)
Belantamab + bortezomib (BVd)	Relapse (outside the US mainly)	DREAMM-7^[38]: median PFS 37 vs 13 months	Corneal toxicity: eye checks
Talquetamab (GPRC5D)	After BCMA therapy	MonumenTAL-1^[42]	Taste, skin and nail changes; weight loss

Table D. Managing problems during treatment

Problem	Prevent	Recognise	Act
Bacterial infection	Levofloxacin first 3 months; vaccines	Fever, cough, burning urine	Same-day assessment; IVIG if IgG low and recurrent
Herpes zoster	Aciclovir/valaciclovir with PIs and anti-CD38	Painful band-like rash	Treatment-dose antiviral
Venous thrombosis	Aspirin or anticoagulant with IMiDs (SAVED, IMPEDE VTE)	Leg swelling, breathlessness	Anticoagulate; continue until 1–3 months after IMiD
Peripheral neuropathy	Subcutaneous, weekly bortezomib; avoid in pre-existing neuropathy	Numbness, burning, unsteadiness	Reduce or hold bortezomib/thalidomide
Kidney injury	Fluids; no NSAIDs or contrast if avoidable	Less urine, rising creatinine	Urgent anti-myeloma therapy; correct calcium
Hypercalcaemia	Effective therapy; avoid dehydration	Thirst, vomiting, confusion, constipation	Fluids, steroids, zoledronic acid (denosumab if refractory)
Jaw osteonecrosis	Dental clearance before; avoid extractions	Exposed bone, jaw pain	Stop the bone drug; dental/oral surgery care
Cord compression	Imaging for new back pain	Back pain, leg weakness, bladder change	MRI within 24 h, dexamethasone, RT; surgery if retropulsed bone
CRS / ICANS (CAR-T, bispecifics)	Step-up dosing; trained centre	Fever, low BP, low oxygen; confusion, writing change	Tocilizumab, steroids per grade
Cardiac events (carfilzomib)	Blood pressure control	Breathlessness, chest pain	Hold drug; cardiology

07 Management algorithms

Five decision paths pull together sections 02–06.

Algorithm 1Suspected plasma cell disorder: to a named diagnosis

Back pain with anaemia, raised protein or ESR, unexplained kidney injury, high calcium, lytic lesion, recurrent infections → CBC, calcium, creatinine, SPEP + immunofixation, serum free light chains, immunoglobulins

Protein found

24-h urine PEP + IFE

Low-risk MGUS (IgG <1.5 g/dL, normal ratio, no CRAB) → no marrow, no imaging

Others → marrow (CD138/flow, FISH) + low-dose CT, PET-CT or MRI

IgM → Waldenström pathway; albuminuria or heart failure → AL

Classify

M <3 g/dL, marrow <10% → MGUS

M ≥3 g/dL or 10–59% → SMM

≥10% or plasmacytoma + CRAB or SLiM → myeloma

SLiM: ≥60% cells · ratio ≥100 · >1 MRI lesion

One lesion only

Biopsy the lesion (never fix first)

Marrow: no clonal cells → solitary plasmacytoma; <10% → minimal marrow involvement

PET-CT ± MRI: no other lesion

≥10% clonal cells = myeloma

All: protect the kidneys (no NSAIDs, no dehydration) while tests run · MRI the whole spine within 24 h for back pain with weakness.

Algorithm 2Newly diagnosed myeloma, transplant eligible

Active myeloma, fit for HCT → FISH risk, kidneys, neuropathy, clot and infection risk; bone drug, dental check, prophylaxis

Induction

D-VRd or Isa-VRd × 3–6 cycles

No quadruplet → VRd

Limited resources → VTd or VCd

No melphalan before collection

Transplant

Collect stem cells (two transplants if under 65)

Standard risk → early HCT or store cells

High risk → early HCT

High-dose melphalan

IFM 2009 · DETERMINATION

Maintenance

Standard → lenalidomide ~2 years (± anti-CD38)

High → lenalidomide + bortezomib to progression

Response checks every 1–3 months

Limited resources: thalidomide or lenalidomide

All: weekly dexamethasone · subcutaneous bortezomib · aspirin or anticoagulant with IMiDs · levofloxacin first 3 months · aciclovir · vaccines.

Algorithm 3Newly diagnosed myeloma, not transplant eligible

Active myeloma, not fit for HCT (or HCT deferred) → frailty assessment, kidneys, neuropathy, resources

Fit

D-VRd or Isa-VRd

8–12 cycles

Then lenalidomide-based maintenance (+ anti-CD38)

CEPHEUS · IMROZ

Frail or neuropathy

DRd (dexamethasone-sparing) or dose-reduced VRd or IsaRd

Rd if a triplet is not tolerated

MAIA: OS benefit with DRd

Limited resources

Bortezomib available → VCd or VTd (VRd if possible)

Not available → CTd or MPT

8–12 cycles, then observe or maintain

VCd if kidney injury or high clot risk

All: treat now (untreated symptomatic myeloma kills within a year) · bone drug by creatinine clearance · clot and infection prevention.

Algorithm 4Relapsed myeloma

Biochemical or clinical relapse confirmed → refractory to which classes? FISH again, organ function, infection risk, CAR-T or second HCT eligibility

First relapse

Fit, access → cilta-cel, teclistamab + daratumumab or BVd

Frail or infection-prone → triplet of unused classes

Stored cells + long remission → second HCT

CARTITUDE-4 · MajesTEC-3 · DREAMM-7

Second or later

BCMA if not yet used: CAR-T, bispecific or belantamab

After BCMA: talquetamab

Trials encouraged

Few options left

Any → selinexor-based or alkylator regimens

t(11;14) → venetoclax

Palliative RT, best supportive care

Goals-of-care discussion

All: CRS and ICANS training for T-cell therapies · IVIG if IgG low · PJP and antiviral prophylaxis · eye checks with belantamab.

Algorithm 5Precursors and solitary plasmacytoma

No myeloma-defining event → what is it, and how risky?

MGUS

Low risk → tests at 6 months, then every 2–3 years

Others → yearly

Organ damage from the protein → MGRS or other MGCS work-up

No treatment for MGUS itself

Smoldering

MRI; repeat tests in 2–3 months

Low/intermediate → observe every 3–4 months

High (20/2/20) → daratumumab or lenalidomide ± dex, or trial

AQUILA: PFS and OS benefit

Solitary plasmacytoma

Bone → RT 35–50 Gy

Soft tissue → RT 40–50 Gy if not fully excised

Then observe: M protein, light chains, imaging

Minimal marrow involvement: closer watch

All: educate about red-flag symptoms · bone drug only for osteoporosis · progression can be abrupt.

08 Survivorship, follow-up & late effects

Figure 15. Response categories (IMWG 2016, Kumar 2016; UpToDate response review).

Figure 16. Follow-up rhythm (UpToDate response, MGUS and smoldering myeloma reviews). Individualise.

Response (IMWG): partial (≥50% fall), very good partial (≥90%), complete (negative immunofixation, marrow <5%), stringent complete and MRD-negative (1 in 100,000 cells) (Kumar 2016^[49]). MRD-guided decisions remain investigational outside trials.
Monitoring: before each cycle at first (CBC, calcium, creatinine, glucose, M protein and light chains); urine every ~6 months; marrow only to confirm CR or when unsure; imaging for symptoms, plasmacytomas or non-secretory disease.
Late effects: neuropathy (bortezomib, thalidomide), second cancers (lenalidomide after HCT), cataract and diabetes (steroids), jaw osteonecrosis (bone drugs), myeloid neoplasms after HCT, vertebral collapse and height loss, chronic kidney disease.
Living with myeloma: a chronic, relapsing illness managed in lines of treatment. Encourage walking and safe exercise (avoid heavy lifting and twisting with spinal disease), hydration, vaccines, dental care, fall prevention, and honest discussion of goals at each relapse.

09 Landmark trials

Figure 17. How to read a survival curve (illustrative). Use the absolute gap at a fixed time and overall survival, not the median or PFS alone, when weighing benefit against toxicity and cost.

Figure 18. Landmark results as reported in the UpToDate initial treatment, relapsed disease and smoldering myeloma reviews.

PERSEUS^[26] and CEPHEUS^[28]: daratumumab added to VRd → deeper MRD negativity, longer PFS → quadruplet induction for most.
IMROZ^[29]: Isa-VRd vs VRd in transplant-ineligible patients → 5-year PFS 63% vs 45%.
MAIA^[31]: DRd vs Rd in older patients → OS benefit → DRd for the frail and those with neuropathy.
IFM 2009^[32] and DETERMINATION^[33]: early HCT → longer PFS, same OS → timing can be individualised.
CARTITUDE-4^[4] and MajesTEC-3^[5]: BCMA CAR-T and teclistamab plus daratumumab improve OS at first relapse.
AQUILA^[23]: daratumumab in high-risk smoldering myeloma → fewer progressions and better OS → early treatment for high-risk SMM.
TEAMM^[46] and Myeloma IX^[43]: simple supportive care (antibiotic prophylaxis, zoledronic acid) saves lives.

10 Practice pearls & pitfalls

Back pain + anaemia + high ESR or total protein in an adult: SPEP with immunofixation and serum free light chains before more painkillers.
Unexplained kidney injury with bland urine: check free light chains the same day; cast nephropathy is a race against time.
A normal SPEP, a negative dipstick or a normal X-ray does not exclude myeloma.
Image with low-dose whole-body CT, PET-CT or MRI; bone scans miss lytic lesions.
Never fix a solitary bone lesion without a biopsy; never call a plasmacytoma "solitary" without marrow and whole-body imaging.
Most MGUS never progresses: risk-stratify, reassure, and explain red-flag symptoms.
High-risk smoldering myeloma: offer early treatment; low risk: watch.
Avoid NSAIDs, dehydration and contrast in myeloma; dose-adjust lenalidomide and bisphosphonates for kidney function.
Every patient on an IMiD needs clot prevention; every patient starting treatment needs levofloxacin, aciclovir (with PIs and anti-CD38) and vaccines.
Back pain with leg weakness or bladder change: whole-spine MRI within 24 hours and dexamethasone.
At relapse, ask "refractory to what?" before choosing; BCMA-directed therapy improves survival.

11 Case vignettes: lines of management

Nine cases from the clinic.

Case 1Myeloma · back pain · transplant eligible

Six months of "lumbar spondylosis"

58 years, manISS IIStandard risk

A 58-year-old farmer from a village near Nellore has had low back pain for 6 months, treated with diclofenac and physiotherapy. He has lost 4 kg and feels tired. Haemoglobin 8.9 g/dL, ESR 110 mm/h, total protein 9.8 g/dL with albumin 3.1 g/dL, creatinine 1.4 mg/dL, calcium 10.6 mg/dL.

Before you open the answer: what is the likely diagnosis, what must be done before treatment, and what is the plan?

Show the line of management

Suspect
Anaemia, high ESR and a wide globulin gap with back pain: myeloma until proved otherwise. Stop NSAIDs (kidneys).
Diagnose
SPEP: 4.8 g/dL spike, IgG κ on immunofixation; κ/λ ratio 38. Marrow: 42% clonal plasma cells. Low-dose whole-body CT: lytic lesions in L2, pelvis and skull; L2 wedge collapse without canal compromise.
Stage
Beta-2 microglobulin 4.1 mg/L, LDH normal; FISH: hyperdiploid, no del(17p), no high-risk translocation, no 1q gain: standard risk; R-ISS II.
Treat
Quadruplet (D-VRd) if available, otherwise VRd or VTd, for 3–6 cycles; stem cell collection; early or deferred HCT discussed; lenalidomide maintenance for about 2 years. Zoledronic acid after dental check; aspirin; levofloxacin and aciclovir; vaccines; kyphoplasty if L2 pain persists.

Teaching points

Back pain with anaemia and high ESR: test for a monoclonal protein.
Use CT, PET-CT or MRI, not X-rays.
Transplant eligibility is about fitness, not age.

See: Sections 02, 03 and 06, Algorithm 2.

Case 2Light-chain myeloma · kidney injury

Vomiting, confusion and a creatinine of 6

66 years, womanLight chain κCast nephropathy

A 66-year-old has 2 weeks of vomiting, thirst and confusion after taking painkillers for rib pain. Creatinine 6.2 mg/dL (normal 3 months ago), calcium 13.1 mg/dL, haemoglobin 9.4 g/dL. Urine dipstick: trace protein only. SPEP: no spike.

Before you open the answer: what is the likely diagnosis, what must be done before treatment, and what is the plan?

Show the line of management

Suspect
Acute kidney injury with high calcium, anaemia and bland urine: light-chain cast nephropathy. A negative SPEP and dipstick do not exclude it.
Diagnose
Serum free κ 4800 mg/L, λ 9 mg/L (ratio >500); urine immunofixation: free κ. Marrow 55% κ-restricted plasma cells. Very high light chains and no other cause: biopsy can be deferred.
Treat today
Isotonic fluids, then fluids for ~3 L urine a day; glucocorticoids; zoledronic acid is avoided (clearance <30) → denosumab or calcitonin bridge; stop NSAIDs; start bortezomib + dexamethasone ± daratumumab at once. Dialysis only for usual indications.
Then
Goal: rapid fall in free κ. Plasma exchange or high cut-off dialysis debated. Many recover kidney function; dose-adjust lenalidomide later; transplant still possible with good recovery.

Teaching points

Unexplained AKI: free light chains on day 1.
Treat the clone fast: kidney recovery depends on it.
Denosumab rather than a bisphosphonate when clearance ≤30.

See: Sections 02, 03 and 06 (kidney), Algorithm 1.

Case 3MGUS · low risk

An incidental band on a health check

61 years, manIgG κ 0.7 g/dLNormal ratio

A 61-year-old bank manager had SPEP at a corporate health check because total protein was 8.4 g/dL. A 0.7 g/dL IgG κ band was found. He is well; CBC, calcium and creatinine are normal.

Before you open the answer: what is the likely diagnosis, what must be done before treatment, and what is the plan?

Show the line of management

Classify
IgG, <1.5 g/dL, normal free light-chain ratio, no CRAB features: low-risk MGUS (20-year progression about 5%).
Avoid harm
No marrow biopsy and no imaging needed; no treatment; no bone drug unless osteoporosis.
Follow
Repeat SPEP, light chains, CBC, calcium and creatinine at 6 months; if stable, every 2–3 years.
Educate
Report new bone pain, fatigue, frothy or reduced urine, numbness or infections promptly; progression can be abrupt.

Teaching points

Most MGUS never progresses.
Three risk factors guide follow-up intensity.
Over-investigation and over-labelling harm patients.

See: Section 06 (MGUS), Algorithm 5.

Case 4Smoldering myeloma · high risk

A large protein, no symptoms

54 years, woman20/2/20: 3 factorsMRI clear

A 54-year-old teacher is found to have an IgA λ protein of 3.4 g/dL during evaluation of a raised ESR. She is well. Haemoglobin, calcium and creatinine are normal.

Before you open the answer: what is the likely diagnosis, what must be done before treatment, and what is the plan?

Show the line of management

Work up
Marrow: 30% clonal plasma cells (no ≥60%); light-chain ratio 26 (not ≥100); whole-body MRI: no focal lesions; low-dose CT: no lytic lesions. Smoldering myeloma.
Stratify
Plasma cells >20%, M protein >2 g/dL, ratio >20: all three 20/2/20 factors = high risk.
Decide
Discuss early treatment: daratumumab for up to 3 years (AQUILA: better PFS and OS) or lenalidomide-based therapy if that is what is available; a trial if one exists. Full myeloma regimens are not used.
Follow
If she declines: tests every 3–4 months and yearly MRI, with clear red-flag advice.

Teaching points

SMM is a spectrum: 20/2/20 separates watch from treat.
SLiM features make it myeloma, not SMM.
Early treatment of high-risk SMM improves survival.

See: Section 06 (smoldering), Algorithm 5.

Case 5Solitary plasmacytoma of bone

Mid-back pain and a collapsed vertebra

47 years, manT9 lesionMarrow clean

A 47-year-old electrician has 2 months of mid-back pain. MRI: a destructive T9 lesion with mild epidural extension, no cord signal change, no weakness.

Before you open the answer: what is the likely diagnosis, what must be done before treatment, and what is the plan?

Show the line of management

Diagnose
CT-guided biopsy: sheets of λ-restricted plasma cells (CD138+). Marrow aspirate and biopsy: no clonal plasma cells. PET-CT and whole-spine MRI: no other lesion. Small IgG λ band; no CRAB.
Stabilise
SINS score and spinal surgery opinion: stable; dexamethasone not needed (no deficit).
Treat
Involved-site RT 40–45 Gy over about 4 weeks covering T8–T10 with margin; no chemotherapy, no bisphosphonate.
Follow
M protein and light chains every 3–6 months, imaging if symptoms; persistence of the M protein at 1 year increases myeloma risk; half or more eventually develop myeloma.

Teaching points

Biopsy before fixation or RT.
Solitary needs marrow and whole-body imaging to prove it.
RT 35–50 Gy cures some; follow for life.

See: Sections 03, 05 and 06, Algorithm 5.

Case 6Solitary extramedullary plasmacytoma

Nose bleeds and a blocked nostril

52 years, manNasal cavityIncompletely excised

A 52-year-old shopkeeper has had right nasal obstruction and recurrent epistaxis for 4 months. An ENT surgeon removed a "polyp" piecemeal; histology shows plasma cells.

Before you open the answer: what is the likely diagnosis, what must be done before treatment, and what is the plan?

Show the line of management

Confirm
Immunohistochemistry: CD138+, κ-restricted plasma cells; exclude MALT lymphoma with plasmacytic differentiation (CD20, light chains, flow).
Stage
PET-CT: residual nasal disease only; marrow <5% polyclonal plasma cells; no M protein; normal CBC, calcium, creatinine.
Treat
Involved-site RT 40–50 Gy (incompletely excised); no chemotherapy.
Follow
Local recurrence <7%; about 10–15% develop myeloma; median survival over 10 years. ENT review and blood tests every 3–6 months at first.

Teaching points

Nasal "polyp" with plasma cells: full staging before calling it solitary.
Incomplete excision → RT 40–50 Gy.
SEP behaves better than SPB.

See: Sections 02, 05 and 06, Algorithm 5.

Case 7Myeloma · frail older adult

Fatigue, falls and an IgA protein

78 years, womanFrailNeuropathy (diabetes)

A 78-year-old widow with diabetic neuropathy, two recent falls and haemoglobin 8.6 g/dL has IgA κ myeloma (2.9 g/dL) with lytic lesions and 35% marrow plasma cells. Creatinine clearance 45 mL/min. She lives with her son.

Before you open the answer: what is the likely diagnosis, what must be done before treatment, and what is the plan?

Show the line of management

Assess
Frailty assessment (age, function, comorbidity): frail. Not a transplant candidate. FISH: t(11;14), standard risk.
Treat
DRd with early stopping of dexamethasone (avoids bortezomib neuropathy; MAIA OS benefit), doses adjusted for kidney function; if daratumumab is unaffordable: dose-reduced Rd or VCd with subcutaneous weekly bortezomib if neuropathy allows.
Prevent
Aspirin with lenalidomide (SAVED low); levofloxacin for 3 months; aciclovir with daratumumab; vaccines; zoledronic acid with dental check; fall prevention, vitamin D and calcium.
Plan
Lenalidomide maintenance as tolerated; t(11;14) noted for venetoclax at relapse.

Teaching points

Frailty, not age, decides intensity.
DRd suits neuropathy and older patients.
Supportive care prevents early deaths.

See: Sections 04 and 06, Algorithm 3.

Case 8Myeloma · first relapse

Rising protein on maintenance

55 years, manLenalidomide-refractoryPost-HCT

A 55-year-old engineer received VRd, autologous HCT and lenalidomide maintenance. At 30 months his IgG rises from 0.2 to 1.4 g/dL over two visits, with new rib pain.

Before you open the answer: what is the likely diagnosis, what must be done before treatment, and what is the plan?

Show the line of management

Confirm
Progression (≥25% rise, ≥0.5 g/dL absolute, new rib lesion on PET-CT): clinical relapse on lenalidomide = lenalidomide-refractory. Repeat FISH: new 1q gain.
Options
BCMA-directed: cilta-cel (CARTITUDE-4) at a CAR-T centre, teclistamab plus daratumumab (MajesTEC-3), or BVd (DREAMM-7). Alternatives if not accessible: DPd, DKd or KPd.
Safety
CRS/ICANS monitoring with T-cell therapies; IVIG for low IgG; PJP and antiviral prophylaxis; eye checks with belantamab.
Also
Palliative RT 8 Gy single fraction to the painful rib; continue zoledronic acid.

Teaching points

Ask "refractory to what?" at every relapse.
BCMA-directed therapy improves survival from first relapse.
Refer early for cellular therapy.

See: Section 06 (relapse), Algorithm 4.

Case 9Emergency · cord compression

Back pain, then weak legs

69 years, manKnown myelomaT6 compression

A 69-year-old on VRd for myeloma reports worsening thoracic back pain for a week and, since yesterday, difficulty climbing stairs and passing urine.

Before you open the answer: what is the likely diagnosis, what must be done before treatment, and what is the plan?

Show the line of management

Recognise
Back pain then weakness and urinary retention: epidural spinal cord compression until proved otherwise.
Image
MRI of the whole spine with contrast within 24 hours (transfer if needed): T6 plasmacytoma compressing the cord; no retropulsed bone.
Treat
Dexamethasone at once; urgent RT with fractionation (better motor recovery); spinal surgery if the spine is unstable, bone is in the canal or weakness progresses; systemic therapy continued or intensified.
Support
Bladder catheter, bowel care, pressure care, clot prevention, physiotherapy and rehabilitation.

Teaching points

Motor outcome depends on how fast you act.
Image the whole spine, not one level.
Most myeloma compressions respond to RT plus dexamethasone.

See: Sections 05 and 06, Algorithm 1.

12 References & guidelines

NCCN Guidelines: Multiple Myeloma, and Systemic Light Chain Amyloidosis/Waldenström for the differentials (current versions); International Myeloma Working Group and IMS/IMWG consensus papers listed below; ILROG radiotherapy guidelines; WHO Classification 5th edition and the International Consensus Classification (2022).
Cross-checked in October 2026 against 28 UpToDate topic reviews: multiple myeloma: clinical features, laboratory manifestations and diagnosis; pathobiology; staging and prognostic studies; overview of management; initial treatment; use of hematopoietic cell transplantation; determining eligibility for autologous HCT; treatment of relapsed disease; evaluating response to treatment; administration considerations for common therapies; treatment protocols; management in resource-limited settings; the use of osteoclast inhibitors; prevention of venous thromboembolism; infections in patients with multiple myeloma; kidney disease in myeloma and other monoclonal gammopathies (etiology and evaluation; treatment and prognosis); monoclonal gammopathy of renal significance; clinical presentation and evaluation, and management, of pathologic fractures; neoplastic epidural spinal cord compression; radiation therapy for painful bone metastases; laboratory methods for analyzing monoclonal proteins; diagnosis of MGUS; clinical course and management of MGUS; smoldering multiple myeloma; solitary plasmacytoma of bone; solitary extramedullary plasmacytoma. All trial citations below come from the reference lists of these reviews; the three Indian papers were found and verified by web search on 17 October 2026.
Reviewed and approved by Dr. Haritha Chiramana, 17 October 2026.

Core trials and papers cited on this page (54)

Journal, year, volume and first page (or DOI); each links to PubMed.

Numbered in order of first citation in the text

MGUS precedes myeloma (Landgren 2009): Landgren O, Kyle RA, Pfeiffer RM, et al. Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study. Blood 2009;113:5412. PubMed MGUS, smoldering myeloma and solitary plasmacytoma
IMWG diagnostic criteria (Rajkumar 2014): Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 2014;15:e538. PubMed Diagnosis, imaging, staging and response
IMS/IMWG high-risk definition (Avet-Loiseau 2025): Avet-Loiseau H, Davies FE, Samur MK, et al. IMS/IMWG consensus recommendations on the definition of high-risk multiple myeloma. J Clin Oncol 2025;43:2739. PubMed Diagnosis, imaging, staging and response
CARTITUDE-4 OS (Einsele 2026): Einsele H, San-Miguel J, Dhakal B, et al. Cilta-cel in lenalidomide-refractory multiple myeloma (CARTITUDE-4): updated analysis including overall survival. Lancet Oncol 2026;27:254. PubMed Relapsed myeloma
MajesTEC-3 (Costa 2026): Costa LJ, Bahlis NJ, Perrot A, et al. Teclistamab plus daratumumab in relapsed or refractory multiple myeloma. N Engl J Med 2026;394:739. PubMed Relapsed myeloma
Presentation of 1027 patients (Kyle 2003): Kyle RA, Gertz MA, Witzig TE, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc 2003;78:21. PubMed Diagnosis, imaging, staging and response
MGUS prevalence (Kyle 2006): Kyle RA, Therneau TM, Rajkumar SV, et al. Prevalence of monoclonal gammopathy of undetermined significance. N Engl J Med 2006;354:1362. PubMed MGUS, smoldering myeloma and solitary plasmacytoma
SMM natural history (Kyle 2007): Kyle RA, Remstein ED, Therneau TM, et al. Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma. N Engl J Med 2007;356:2582. PubMed MGUS, smoldering myeloma and solitary plasmacytoma
Myeloma outcomes in North India (Yanamandra 2021): Yanamandra U, Sharma R, Shankar S, et al. Survival outcomes of newly diagnosed multiple myeloma at a tertiary care center in North India (IMAGe: 001A study). JCO Glob Oncol. 2021. doi:10.1200/GO.20.00625. PubMed India
Myeloma cytogenetics in Eastern India (Jha 2023): Jha et al. Cytogenetic alterations and correlation with age and gender in patients of multiple myeloma: a study from a tertiary care center in Eastern India. Indian J Med Paediatr Oncol. 2023. doi:10.1055/s-0043-1761441. PubMed India
IMWG imaging consensus (Hillengass 2019): Hillengass J, Usmani S, Rajkumar SV, et al. International Myeloma Working Group consensus recommendations on imaging in monoclonal plasma cell disorders. Lancet Oncol 2019;20:e302. PubMed Diagnosis, imaging, staging and response
Solitary plasmacytoma: European panel (Caers 2018): Caers J, Paiva B, Zamagni E, et al. Diagnosis, treatment, and response assessment in solitary plasmacytoma: updated recommendations from a European Expert Panel. J Hematol Oncol 2018;11:10. PubMed MGUS, smoldering myeloma and solitary plasmacytoma
R-ISS (Palumbo 2015): 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;33:2863. PubMed Diagnosis, imaging, staging and response
R2-ISS (D'Agostino 2022): D'Agostino M, Cairns DA, Lahuerta JJ, et al. Second revision of the International Staging System (R2-ISS) for overall survival in multiple myeloma. J Clin Oncol 2022;40:3406. PubMed Diagnosis, imaging, staging and response
ILROG plasmacytoma and myeloma RT (Tsang 2018): Tsang RW, Campbell BA, Goda JS, et al. Radiation therapy for solitary plasmacytoma and multiple myeloma: guidelines from the International Lymphoma Radiation Oncology Group. Int J Radiat Oncol Biol Phys 2018;101:794. PubMed MGUS, smoldering myeloma and solitary plasmacytoma
Rare Cancer Network plasmacytoma (Ozsahin 2006): Ozsahin M, Tsang RW, Poortmans P, et al. Outcomes and patterns of failure in solitary plasmacytoma: a multicenter Rare Cancer Network study of 258 patients. Int J Radiat Oncol Biol Phys 2006;64:210. PubMed MGUS, smoldering myeloma and solitary plasmacytoma
Palliative RT 8 Gy vs 30 Gy (Rudzianskiene 2017): Rudzianskiene M, Inciura A, Gerbutavicius R, et al. Single vs. multiple fraction regimens for palliative radiotherapy treatment of multiple myeloma: a prospective randomised study. Strahlenther Onkol 2017;193:742. PubMed Supportive care
CAFE kyphoplasty (Berenson 2011): Berenson J, Pflugmacher R, Jarzem P, et al. Balloon kyphoplasty versus non-surgical fracture management for painful vertebral body compression fractures in patients with cancer. Lancet Oncol 2011;12:225. PubMed Supportive care
MGUS risk model (Rajkumar 2005): Rajkumar SV, Kyle RA, Therneau TM, et al. Serum free light chain ratio is an independent risk factor for progression in MGUS. Blood 2005;106:812. PubMed MGUS, smoldering myeloma and solitary plasmacytoma
MGUS long-term follow-up (Kyle 2018): Kyle RA, Larson DR, Therneau TM, et al. Long-term follow-up of monoclonal gammopathy of undetermined significance. N Engl J Med 2018;378:241. PubMed MGUS, smoldering myeloma and solitary plasmacytoma
SMM 20/2/20 model (Lakshman 2018): Lakshman A, Rajkumar SV, Buadi FK, et al. Risk stratification of smoldering multiple myeloma incorporating revised IMWG diagnostic criteria. Blood Cancer J 2018;8:59. PubMed MGUS, smoldering myeloma and solitary plasmacytoma
IMWG SMM risk model (Mateos 2020): Mateos MV, Kumar S, Dimopoulos MA, et al. International Myeloma Working Group risk stratification model for smoldering multiple myeloma. Blood Cancer J 2020;10:102. PubMed MGUS, smoldering myeloma and solitary plasmacytoma
AQUILA (Dimopoulos 2025): Dimopoulos MA, Voorhees PM, Schjesvold F, et al. Daratumumab or active monitoring for high-risk smoldering multiple myeloma. N Engl J Med 2025;392:1777. PubMed MGUS, smoldering myeloma and solitary plasmacytoma
E3A06 (Lonial 2020): Lonial S, Jacobus S, Fonseca R, et al. Randomized trial of lenalidomide versus observation in smoldering multiple myeloma. J Clin Oncol 2020;38:1126. PubMed MGUS, smoldering myeloma and solitary plasmacytoma
QuiRedex (Mateos 2013): Mateos MV, Hernández MT, Giraldo P, et al. Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma. N Engl J Med 2013;369:438. PubMed MGUS, smoldering myeloma and solitary plasmacytoma
PERSEUS (Sonneveld 2024): Sonneveld P, Dimopoulos MA, Boccadoro M, et al. Daratumumab, bortezomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med 2024;390:301. PubMed First-line treatment, transplant and maintenance
GMMG-HD7 (Goldschmidt 2022): Goldschmidt H, Mai EK, Bertsch U, et al. Addition of isatuximab to lenalidomide, bortezomib, and dexamethasone as induction therapy (GMMG-HD7). Lancet Haematol 2022;9:e810. PubMed First-line treatment, transplant and maintenance
CEPHEUS (Usmani 2025): Usmani SZ, Facon T, Hungria V, et al. Daratumumab plus bortezomib, lenalidomide and dexamethasone for transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma: the CEPHEUS trial. Nat Med 2025;31:1195. PubMed First-line treatment, transplant and maintenance
IMROZ (Facon 2024): Facon T, Dimopoulos MA, Leleu XP, et al. Isatuximab, bortezomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med 2024;391:1597. PubMed First-line treatment, transplant and maintenance
SWOG S0777 (Durie 2017): Durie BG, Hoering A, Abidi MH, et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone (SWOG S0777). Lancet 2017;389:519. PubMed First-line treatment, transplant and maintenance
MAIA OS (Facon 2021): Facon T, Kumar SK, Plesner T, et al. Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): overall survival results. Lancet Oncol 2021;22:1582. PubMed First-line treatment, transplant and maintenance
IFM 2009 (Attal 2017): Attal M, Lauwers-Cances V, Hulin C, et al. Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. N Engl J Med 2017;376:1311. PubMed First-line treatment, transplant and maintenance
DETERMINATION (Richardson 2022): Richardson PG, Jacobus SJ, Weller EA, et al. Triplet therapy, transplantation, and maintenance until progression in myeloma. N Engl J Med 2022;387:132. PubMed First-line treatment, transplant and maintenance
Myeloma XI maintenance (Jackson 2019): Jackson GH, Davies FE, Pawlyn C, et al. Lenalidomide maintenance versus observation for patients with newly diagnosed multiple myeloma (Myeloma XI). Lancet Oncol 2019;20:57. PubMed First-line treatment, transplant and maintenance
ENDURANCE maintenance duration (Kumar 2026): Kumar S, Jacobus S, Cohen A, et al. Continuous or fixed-duration maintenance therapy in multiple myeloma. N Engl J Med 2026;395:221. PubMed First-line treatment, transplant and maintenance
IFM2013-04 VTd vs VCd (Moreau 2016): Moreau P, Hulin C, Macro M, et al. VTD is superior to VCD prior to intensive therapy in multiple myeloma: results of the prospective IFM2013-04 trial. Blood 2016;127:2569. PubMed First-line treatment, transplant and maintenance
Thalidomide maintenance (Ludwig 2010): Ludwig H, Adam Z, Tóthová E, et al. Thalidomide maintenance treatment increases progression-free but not overall survival in elderly patients with myeloma. Haematologica 2010;95:1548. PubMed First-line treatment, transplant and maintenance
DREAMM-7 (Hungria 2024): Hungria V, Robak P, Hus M, et al. Belantamab mafodotin, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med 2024;391:393. PubMed Relapsed myeloma
DREAMM-8 (Dimopoulos 2024): Dimopoulos MA, Beksac M, Pour L, et al. Belantamab mafodotin, pomalidomide, and dexamethasone in multiple myeloma. N Engl J Med 2024;391:408. PubMed Relapsed myeloma
KarMMa-3 (Rodriguez-Otero 2023): Rodriguez-Otero P, Ailawadhi S, Arnulf B, et al. Ide-cel or standard regimens in relapsed and refractory multiple myeloma. N Engl J Med 2023;388:1002. PubMed Relapsed myeloma
MajesTEC-1 (Moreau 2022): Moreau P, Garfall AL, van de Donk NWCJ, et al. Teclistamab in relapsed or refractory multiple myeloma. N Engl J Med 2022;387:495. PubMed Relapsed myeloma
MonumenTAL-1 (Chari 2022): Chari A, Minnema MC, Berdeja JG, et al. Talquetamab, a T-cell-redirecting GPRC5D bispecific antibody for multiple myeloma. N Engl J Med 2022;387:2232. PubMed Relapsed myeloma
Myeloma IX bisphosphonate (Morgan 2010): 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). Lancet 2010;376:1989. PubMed Supportive care
Denosumab vs zoledronic acid (Raje 2018): Raje N, Terpos E, Willenbacher W, et al. Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma. Lancet Oncol 2018;19:370. PubMed Supportive care
MYRE high-cutoff dialysis (Bridoux 2017): Bridoux F, Carron PL, Pegourie B, et al. Effect of high-cutoff hemodialysis vs conventional hemodialysis on hemodialysis independence among patients with myeloma cast nephropathy. JAMA 2017;318:2099. PubMed Supportive care
TEAMM levofloxacin (Drayson 2019): Drayson MT, Bowcock S, Planche T, et al. Levofloxacin prophylaxis in patients with newly diagnosed myeloma (TEAMM). Lancet Oncol 2019;20:1760. PubMed Supportive care
SAVED score (Li 2019): Li A, Wu Q, Luo S, et al. Derivation and validation of a risk assessment model for immunomodulatory drug-associated thrombosis among patients with multiple myeloma. J Natl Compr Canc Netw 2019;17:840. PubMed Supportive care
IMPEDE VTE (Sanfilippo 2019): Sanfilippo KM, Luo S, Wang TF, et al. Predicting venous thromboembolism in multiple myeloma: development and validation of the IMPEDE VTE score. Am J Hematol 2019;94:1176. PubMed Supportive care
IMWG response and MRD criteria (Kumar 2016): Kumar S, Paiva B, Anderson KC, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol 2016;17:e328. PubMed Diagnosis, imaging, staging and response

Further reading (not cited in the text above)

Myeloma care in India: cost and generics (2016 panel): India and Ukraine Haemato-oncology Group, Garg A, et al. Management of multiple myeloma and usage of bortezomib: perspective from India and Ukraine. Front Oncol 6:243. 2016. doi:10.3389/fonc.2016.00243. PubMed India
SPB flow cytometry risk (Paiva 2014): Paiva B, Chandia M, Vidriales MB, et al. Multiparameter flow cytometry for staging of solitary bone plasmacytoma: new criteria for risk of progression to myeloma. Blood 2014;124:1300. PubMed MGUS, smoldering myeloma and solitary plasmacytoma
MAIA (Facon 2019): Facon T, Kumar S, Plesner T, et al. Daratumumab plus lenalidomide and dexamethasone for untreated myeloma. N Engl J Med 2019;380:2104. PubMed First-line treatment, transplant and maintenance
ALCYONE OS (Mateos 2020): Mateos MV, Cavo M, Blade J, et al. Overall survival with daratumumab, bortezomib, melphalan, and prednisone in newly diagnosed multiple myeloma (ALCYONE). Lancet 2020;395:132. PubMed First-line treatment, transplant and maintenance
ENDURANCE (Kumar 2020): Kumar SK, Jacobus SJ, Cohen AD, et al. Carfilzomib or bortezomib in combination with lenalidomide and dexamethasone (ENDURANCE). Lancet Oncol 2020;21:1317. PubMed First-line treatment, transplant and maintenance

How to cite this page

VancouverChiramana H. Multiple Myeloma: a mini review for clinicians. Oncology Knowledge Hub [Internet]. Nellore (India): drharitha.co.in; 2026 [updated 2026 Oct 17; cited year month day]. Available from: https://drharitha.co.in/professionals/multiple-myeloma

APA 7Chiramana, H. (2026, October 17). Multiple Myeloma: A mini review for clinicians. Oncology Knowledge Hub. Retrieved Month Day, Year, from https://drharitha.co.in/professionals/multiple-myeloma

Free to use and share for education with attribution; please do not alter or use commercially (CC BY-NC-ND 4.0). Replace the italic parts with the date you accessed the page.

Educational summary for health professionals, written in our own words from current guidelines and primary trials. No drug doses are given. Hodgkin, aggressive B-cell, indolent B-cell, T-cell and cutaneous lymphomas are parts 1–5; Waldenström macroglobulinaemia is covered in the indolent B-cell module; AL amyloidosis, POEMS syndrome and plasma cell leukaemia are mentioned here only as differentials. Verify current guidelines, Indian regulatory approvals and individual patient factors before treatment decisions.

Written by Dr. Haritha ChiramanaSenior Medical Oncologist & Hemato-Oncologist · MD, DM (Medical Oncology) · C.R. Reddy Cancer Center, Nellore, Andhra Pradesh, India

Medically reviewed by Dr. Haritha Chiramana on 17 October 2026. This page is general education and cannot replace an individual consultation.