GeriQBank · Paper III · Q3
Multiple Myeloma — Aetiology, Diagnosis & Management
- Chapter
- Haematology
- Years asked
- Not recorded in the source
- Frequency
- Not set in Papers III–IV, 2009–2025
Detailed answer
Pro · free in betaAttempt it firstOutline your answer before revealing it — definition, causes, evaluation, management and the geriatric angle.Reveal answer
Textbook gap: No myeloma chapter in Pathy's. Transferable content: Ch. 24 (paraprotein coagulopathy), Anaemia chapter (clonal anaemia), Ch. 59 (spinal red flags), and — most valuably — Ch. 26/27's geriatric-oncology philosophy (CGA is standard of care; treatment must not be chosen on chronological age alone; frailty/comorbidity assessment via gait speed, SPPB, Charlson index, CRASH score, Hurria/CARG tool).
High-Yield Points
A. Definition & Epidemiology
Malignant clonal plasma cell proliferation producing M-protein and end-organ damage.
10–15% of haematological malignancies; median diagnosis age 65–70; >30% of patients >75 years.
B. Aetiology & Risk Factors
Cause unknown; arises from a post-germinal-centre plasma cell; every case preceded by MGUS.
Host factors: age (dominant), male sex, African ancestry (~2× risk, 5–10 yrs earlier), family history (2–3×), obesity/T2DM.
Environmental: ionising radiation, benzene, pesticides/herbicides/dioxins, agriculture/woodworking/paper industry.
Predisposing states: MGUS (~1%/yr progression), smouldering myeloma (~10%/yr), solitary plasmacytoma.
C. Pathogenesis
Primary genetic events (mutually exclusive): hyperdiploidy (55–60%, better prognosis) vs IgH translocations — t(11;14)→CCND1, t(4;14)→NSD2/FGFR3, t(14;16)→MAF.
Secondary events drive progression: MYC rearrangement, RAS mutations, del(17p)/TP53 loss, 1q21 gain.
Marrow microenvironment: IL-6, IGF-1, VEGF from stroma; bone disease from ↑RANKL/MIP-1α + ↓osteoprotegerin (osteoclast activation) and DKK1/IL-3 suppressing osteoblasts — purely lytic lesions, bone scan is falsely negative.
D. Diagnosis
SPEP + immunofixation + serum FLC + 24-hr urine IFE.
Marrow biopsy with flow cytometry and FISH (del17p, t(4;14), t(14;16), t(14;20), 1q gain).
Imaging: WBLDCT/WB-MRI/PET-CT (skeletal survey/bone scan obsolete).
IMWG criteria: ≥10% clonal plasma cells or plasmacytoma + ≥1 myeloma-defining event (CRAB + SLiM).
E. Staging & Management Principles
ISS → R-ISS → R2-ISS; IMWG Frailty Index independently predicts survival/toxicity.
Four rules: treat only symptomatic disease; decide transplant eligibility by fitness not age; CGA/frailty assessment before intensity; supportive care equally important.
Management at a Glance
Setting Approach
Transplant-eligible Quadruplet induction (D-VRd/Isa-VRd) → ASCT (melphalan 200 mg/m²) → lenalidomide ± daratumumab maintenance Transplant- D-VRd (fit, ≤80) or DRd/Isa-Rd (frail), until progression ineligible/older Frail/very elderly Dose-attenuated; SC bortezomib weekly; reduce dexamethasone to 20 mg weekly Relapsed Carfilzomib, pomalidomide, isatuximab, elotuzumab, or cilta-cel CAR-T Triple-class-exposed BCMA CAR-T or bispecifics (teclistamab, elranatamab, talquetamab) Bone disease Zoledronic acid 4mg IV monthly (avoid if eGFR<30) or denosumab 120mg SC monthly Renal impairment Hydration ~3L/day; stop NSAIDs/ACEi/contrast; urgent bortezomib-based therapy Cord compression Emergency — urgent MRI + high-dose dexamethasone + radiotherapy/surgery MD Geriatrics – Haematology Compendium Page 7 of 34 Latest Updates (2023–Present)
PERSEUS (NEJM 2024): D-VRd + Dara-R maintenance gave 4-yr PFS 84.3% vs 67.7% (VRd) — new standard for transplant-eligible. CEPHEUS/IMROZ: quadruplets now standard for transplant-ineligible too (age capped at 80, excludes frail). AURIGA: Dara-R maintenance boosts MRD-negative conversion in post-transplant MRD-positive patients. IMS–IMWG 2025 redefines high-risk myeloma. FDA ODAC (2024) accepts MRD-negative CR as regulatory endpoint; MIDAS (2025) tests transplant omission if MRD-negative. CAR-T/bispecifics transform relapsed disease — bispecifics favoured in frail elderly. AQUILA (2025): daratumumab approved for high-risk SMM. Frailty subgroup analyses of MAIA/IMROZ confirm anti-CD38 benefit persists in frail patients but quadruplets tolerated poorly.
Current Practice Update
Domain Pathy's (2022) Current evidence
Aetiology/diagnosis No content at all Fully defined by IMWG/WHO-HAEM5 First-line therapy Not addressed Quadruplets (D-VRd/Isa-VRd) fit; DRd/Isa-Rd frail Transplant Not myeloma-specific; RIC principle for MDS/AML ASCT melphalan 200mg/m², increasingly deferred if MRD-transfers negative Role of CGA Strongly endorsed for haematological malignancy Formalised as IMWG Frailty Index with frailty-adapted dosing MD Geriatrics – Haematology Compendium Page 8 of 34
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References
- PAPERS-2-3-4_COMBINED.pdf — page 846
- GeriQBank source PDF — p. 846
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