多發性骨髓瘤

Buzzwords → Dx

Diagnostic Criteria (IMWG 2014, refined 2025)

• Active MM = clonal BMPC ≥10 % (or extramedullary plasmacytoma) + ≥1 of:
  • CRAB end-organ damage, OR
  • SLiM biomarker (any one of: BMPC ≥60 %, FLC ratio ≥100, MRI focal lesion >5 mm).
• Smoldering MM (SMM): meets clonal threshold but no CRAB/SLiM. High-risk SMM (Mayo "20-2-20": M-protein >2 g/dL, BMPC >20 %, FLC ratio >20) → consider treatment / trial.
• Solitary plasmacytoma: single lesion (bone or extramedullary), <10 % clonal BMPC, no CRAB.
• AL amyloidosis: Congo-red apple-green birefringence + LC clonality + organ involvement.

Workup

• CBC, BMP, Ca, albumin, LDH, β2-microglobulin, free light chains (sFLC).
• SPE + IFE + UPE/UIFE + sFLC ratio — quantify M-protein (note: daratumumab interferes — see Pearls).
• Bone marrow aspirate + biopsy with FISH for t(4;14), t(14;16), t(14;20), del 17p, gain/amp 1q21, t(11;14).
• Whole-body low-dose CT (or PET-CT) — preferred over skeletal survey; MRI spine + pelvis if suspected SMM/solitary plasmacytoma.
• Echo + cardiac MRI + NT-proBNP, troponin if AL amyloid suspected.
• 24-hr urine for protein quantification (vs nephrotic-range proteinuria of AL).
• HBV/HCV/HIV serology, echo/MUGA before anthracycline.
• Type & screen BEFORE first daratumumab dose (avoids panagglutination later).

Treatment Algorithm

flowchart TD
  A[Active MM<br>≥10% BMPC + SLiM-CRAB] --> B{Frailty assessment<br>fit / unfit / frail?}
  B -- fit / transplant-eligible --> C[Quadruplet induction<br>Dara-VRd PERSEUS<br>or Isa-VRd]
  B -- non-frail<br>not transplant --> D[Quadruplet OR triplet<br>Dara-VRd CEPHEUS &lt;80<br>or DRd MAIA]
  B -- frail --> E[VRd-lite<br>or DRd]
  C --> F[Stem cell collection<br>before prolonged Len/Dara]
  F --> G[ASCT consolidation]
  G --> H{Risk?}
  D --> H
  E --> H
  H -- standard --> I[Lenalidomide maintenance<br>category 1]
  H -- high-risk --> J[Dara-Len<br>or Bortezomib + Len]
  I --> K{Relapse?}
  J --> K
  K -- ≥1 prior line<br>Len-refractory --> L[Cilta-cel CAR-T<br>CARTITUDE-4 — OS benefit]
  K -- ≥2 prior lines<br>triple-class exposed --> M[Ide-cel CAR-T<br>KarMMa-3]
  K -- ≥4 prior lines --> N[BCMA bispecifics<br>teclistamab / elranatamab<br>or GPRC5D talquetamab]

Pearls / Pitfalls

• SLiM defines active MM by itself. Any one of (BMPC ≥60 %, FLC ratio ≥100, >1 MRI focal lesion ≥5 mm) qualifies — do NOT wait for CRAB end-organ damage to start treatment. The board trap is "patient has BMPC 65 % but no CRAB; defer therapy." Wrong — start treatment.⁴
• R2-ISS now includes 1q+ (0.5 pts). Old R-ISS did not. Sole 1q21 alone is not "high-risk" per NCCN, but it adds 0.5 to R2-ISS score and worsens prognosis when combined with other CAs.⁵
• Lenalidomide maintenance increases SPM risk. Hematologic SPM ~7.5 % vs 3.3 % placebo post-ASCT; overall SPM ~14.9 % vs 8.8 % at long follow-up. PFS/OS benefit still outweighs — but counsel patients and continue surveillance.⁶
• Daratumumab dual lab interference — board favorite:
  • (1) Type & screen panagglutination: binds CD38 on reagent RBCs → false-positive indirect Coombs. Get a baseline T&S BEFORE first dose; mitigate with DTT-treated panel cells (denatures CD38) or anti-idiotype antibody.
  • (2) SPE/IFE interference: appears as IgG-kappa band, mimics residual M-protein → confounds CR/sCR assessment. Use mass-spec–based assays (e.g., MASS-FIX) or DIRA assay to differentiate.⁷
• Plasma-cell leukemia threshold lowered to ≥5 % circulating PCs (was 2 × 10⁹/L absolute count). NCCN/IMWG 2025 — likely board-relevant update.⁸
• AL amyloid clincher = periorbital purpura + macroglossia. Nephrotic-range proteinuria + low-voltage ECG + restrictive CMP completes the gestalt. Factor X deficiency (Xa adsorption by amyloid) → don't miss the bleeding diathesis.

Cross-references

• MGUS / SMM differentials
• AL Amyloidosis
• Waldenström — competing IgM gammopathy
• Cytogenetics Atlas — t(4;14), t(11;14), del(17p), 1q+
• Drug Regimens — Dara-VRd, DRd, Cilta-cel
• Staging — ISS, R-ISS, R2-ISS
• BCMA CAR-T (cilta-cel, ide-cel)
• Hypercalcemia of malignancy

相關題目

• Q-058 — MM — SLiM criterion as myeloma-defining event
• Q-059 — MM — frontline therapy in transplant-eligible patient
• Q-060 — MM — daratumumab and type & screen interference
• Q-145 — Auto-HCT in MM — conditioning regimen
• Q-184 — Cord compression — initial management
• Q-190 — Hypercalcemia of malignancy — first-line therapy
• Q-191 — Hypercalcemia — denosumab in renal failure
• Q-212 — Bone pain in MM — multimodal management

Sources

Drafted from OpenEvidence query 2026-05-07; cross-checked against NCCN MM 2026-01 and CARTITUDE-4 OS update.