GeriQBank · Paper III · Q2
Plasma Cell Dyscrasias — Clinical Presentation, Diagnostic Criteria, Progression & Treatment
- Chapter
- Haematology
- Years asked
- Not recorded in the source
- Frequency
- Not set in Papers III–IV, 2009–2025
Detailed answer
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Textbook gap: No dedicated Pathy's content. Relevant fragments: Ch. 24 (paraprotein-related coagulation defects), Anaemia chapter (MGUS as clonal anaemia), Ch. 59 (chronic pain red flags — weight loss, fever, prior malignancy, progressive neurological deficit — directly applicable to myeloma back pain).
High-Yield Points
A. Clinical Presentation
MGUS/smouldering myeloma usually found incidentally on routine SPEP or a raised globulin gap/unexplained high ESR.
Symptomatic myeloma = CRAB tetrad (hyperCalcaemia, Renal impairment, Anaemia, Bone lesions) — present in ~80% at diagnosis.
Bone pain is commonest — back/rib pain, vertebral fractures, height loss, spinal cord compression (emergency).
Anaemia in ~70% — normocytic; in the elderly presents as fatigue, falls, delirium, functional decline; film shows rouleaux.
Renal impairment in 20–40% — mainly light-chain cast nephropathy, worsened by hypercalcaemia, dehydration, NSAIDs, contrast.
Recurrent infection from immune paresis (suppressed uninvolved immunoglobulins); encapsulated organisms predominate.
Syndrome-specific: hyperviscosity (Waldenström's), neuropathy (POEMS/anti-MAG), nephrotic syndrome/macroglossia (AL amyloidosis).
In the elderly, presentation is often non-specific — falls, delirium, weight loss, or a persistently raised ESR.
B. Diagnostic Criteria
Screening: SPEP + serum immunofixation + serum free light chain (FLC) assay, plus 24-hr urine electrophoresis/IFE for Bence Jones protein.
Bone marrow aspirate/biopsy with flow cytometry (CD38 bright, CD138+) and FISH (del17p, t(4;14), t(14;16), 1q gain).
Imaging: whole-body low-dose CT, whole-body MRI, or PET-CT. Plain skeletal survey is obsolete.
MGUS = M-protein <3 g/dL, marrow plasma cells <10%, no end-organ damage.
Smouldering myeloma = M-protein ≥3 g/dL (or urine ≥500 mg/24h) or plasma cells 10–60%, no MDE.
Multiple myeloma (IMWG) = ≥10% clonal plasma cells or plasmacytoma + ≥1 myeloma-defining event.
MDE = CRAB + SLiM: Ca >11 mg/dL; creatinine >2 mg/dL or CrCl <40 mL/min; Hb <10 g/dL; ≥1 lytic lesion; ≥60% plasma cells; FLC ratio ≥100; >1 MRI focal lesion.
C. Progression
Stepwise: normal → MGUS → smouldering myeloma → symptomatic myeloma → plasma cell leukaemia/extramedullary disease.
Rates: MGUS ~1%/year (lifelong); SMM ~10%/year (first 5 yrs), then ~3%, then ~1%/year.
Risk models: Mayo MGUS model (M-protein ≥1.5 g/dL, non-IgG, abnormal FLC ratio); "20-2-20" SMM model (plasma cells >20%, M-protein >2 g/dL, FLC ratio >20).
Staging: ISS → R-ISS → R2-ISS. IMWG Frailty Index independently predicts survival/toxicity in the elderly.
Treatment at a Glance
Condition Standard approach
MGUS (low risk) Observation; repeat SPEP+FLC at 6 months then 1–2 yearly Smouldering myeloma (high risk) Subcutaneous daratumumab (2025) or trial Myeloma, fit/transplant-eligible Quadruplet induction → ASCT → lenalidomide maintenance Myeloma, transplant-ineligible D-VRd (fit) or DRd/Isa-Rd (frail), until progression Myeloma, frail/very old Dose-attenuated doublet/triplet; treat to tolerability MD Geriatrics – Haematology Compendium Page 5 of 34 Relapsed/refractory BCMA CAR-T (cilta-cel, ide-cel) or bispecifics (teclistamab, elranatamab) Supportive care Zoledronic acid/denosumab, hydration, avoid NSAIDs/contrast, VTE prophylaxis with IMiDs AL amyloidosis Dara-VCd (first-line)
Waldenström's Zanubrutinib or bendamustine-rituximab; plasmapheresis for hyperviscosity Latest Updates (2023–Present)
CEPHEUS (Nat Med 2025): D-VRd gave MRD-negativity 60.9% vs 39.5%, 43% lower progression/death risk in transplant-ineligible myeloma. IMROZ (NEJM 2024): Isa-VRd gave 5-yr PFS 63% vs 45%. Both capped age at 80 and excluded frail patients — DRd/Isa-Rd remain preferred for the truly frail. AQUILA (NEJM 2025): daratumumab in high-risk SMM, FDA-approved Nov 2025 — shift to early interception. IMS–IMWG 2025 redefines high-risk myeloma (~20–25% of patients): del17p/TP53, t(4;14)/t(14;16) with 1q gain, high β2-microglobulin with normal creatinine. FDA ODAC (April 2024) voted MRD-negative CR an acceptable endpoint for accelerated approval; MIDAS trial (NEJM 2025) tested whether MRD-negative patients can skip transplant. CAR-T/bispecifics now give 60–97% response in triple-class-exposed disease; bispecifics often preferred in frail elderly (off-the-shelf, no apheresis). AL amyloidosis: anti-fibril antibodies anselamimab and birtamimab in phase III. Waldenström's: zanubrutinib preferred over ibrutinib (ASPEN — far less AF).
Current Practice Update
Domain Pathy's (2022) Current evidence
Diagnostic criteria Absent CRAB + SLiM biomarkers (IMWG)
Imaging Not addressed Skeletal survey/bone scan obsolete; WBLDCT/WB-MRI/PET-CT standard First-line therapy Not addressed Quadruplets (D-VRd/Isa-VRd) fit; DRd/Isa-Rd frail Precursor treatment Not addressed Daratumumab approved for high-risk SMM (2025)
Relapsed disease Not addressed CAR-T and bispecific antibodies MD Geriatrics – Haematology Compendium Page 6 of 34
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References
- PAPERS-2-3-4_COMBINED.pdf — page 844
- GeriQBank source PDF — p. 844
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