Clinical Commander

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heme.multiple-myeloma.chronic.v1

Multiple Myeloma (initial diagnosis + chronic management)

oncologychronicsubacuteadultoutpatienttransitioninpatient
Start encounter →Print handoutPRODUCTION

STEP 3 deepened 2026-05-16. 2026-05-22 PMID remediation (live PubMed-verified): MAIA 30866031->31141632 (was a glioblastoma review), SWOG S0777 28157635->28017406 (was an organogel chemistry paper), DETERMINATION 36070866->35660812 (was a single-cell RNA-seq paper); IMWG 25439696 + ASPIRE/KRd 25482145 confirmed correct. RxCUI fix: zoledronic_acid 6377 (=levopropoxyphene)->77655. §5.5.1 effect sizes wired (MAIA D-Rd PFS ~61.9 vs 34.4 mo HR ~0.55; SWOG S0777 OS ~75 vs 64 mo; DETERMINATION early-ASCT PFS ~67.5 vs 46.2 mo; CARTITUDE-4 cilta-cel PFS HR ~0.26). §5.5.2 MGUS(~1%/yr)->SMM(~10%/yr)->MM progression continuum + CRAB/SLiM criteria. last_reconciled 2026-05-22. Deepened 2026-05-13: all atoms cited to NCCN 2024 MM, IMWG 2014 Rajkumar Lancet Oncol, IMWG 2020 Kumar Lancet Oncol, GRIFFIN Voorhees Blood 2020, MAIA Facon NEJM 2019, DETERMINATION Richardson NEJM 2022, CALGB 100104 McCarthy NEJM 2012, ASTCT 2019 Lee. Sources workup: workup.mm_initial (IMWG 2014 + NCCN 2024 MM). Key trials: GRIFFIN (TE D-VRD), MAIA (TI D-Rd), DETERMINATION (ASCT benefit), CARTITUDE-4 (cilta-cel), KarMMa-3 (ide-cel), MajesTEC-1 (teclistamab).

Entry points (4)

  • lab_abnormality
    M-protein on SPEP/UPEP/serum free light chain (IMWG 2014 Rajkumar Lancet Oncol)
    monoclonal_gammopathy
  • lab_abnormality
    CRAB: hyperCalcemia / Renal failure / Anemia / Bone lesion (IMWG 2014 Rajkumar Lancet Oncol)
    crab_features
  • symptom
    Bone pain / pathological fracture (NCCN 2024 MM)
    bone_pain
  • lab_abnormality
    Unexplained anemia + elevated total protein (NCCN 2024 MM)
    unexplained_anemia

Required inputs (8)

  • agerequired
    demographic • used at CONTEXT
    Transplant eligibility cutoff + dose adjustments (NCCN 2024 MM; IMWG 2020 Rajkumar)
  • cbc_with_diffrequired
    lab • used at INITIAL_WORKUP
    Anemia (rouleaux), leukopenia, thrombocytopenia; CRAB criteria (IMWG 2014 Rajkumar Lancet Oncol)
  • creatininerequired
    lab • used at INITIAL_WORKUP
    CRAB renal criterion Cr >2 or eGFR <40; cast nephropathy (IMWG 2014 Rajkumar Lancet Oncol)
  • calciumrequired
    lab • used at INITIAL_WORKUP
    CRAB hypercalcemia >11 mg/dL or >1 mg above upper limit (IMWG 2014 Rajkumar Lancet Oncol)
  • spep_upep_sflrequired
    lab • used at INITIAL_WORKUP
    M-protein quantification + Bence Jones; serum free light chain ratio (IMWG 2014 Rajkumar Lancet Oncol; NCCN 2024 MM)
  • whole_body_imagingrequired
    imaging • used at INITIAL_WORKUP
    Whole-body low-dose CT or MRI or PET/CT for lytic lesions CRAB B (IMWG 2014 Rajkumar Lancet Oncol; NCCN 2024 MM)
  • transplant_eligibilityrequired
    history • used at CONTEXT
    Determines D-VRD eligible vs D-Rd ineligible (NCCN 2024 MM; Richardson NEJM 2022 DETERMINATION)
  • bm_biopsy
    lab • used at BRANCHING_WORKUP
    Plasma cell percentage; cytogenetics + FISH for risk stratification (IMWG 2014 Rajkumar Lancet Oncol; NCCN 2024 MM)

12-phase flow (12)

  1. 1FRAME
    Apply IMWG 2014 criteria — CRAB or SLiM biomarkers: >=60% PCs, FLC ratio >=100, MRI >=1 focal lesion (Rajkumar Lancet Oncol 2014)
    inputs: spep_upep_sfl, creatinine, calcium
    advance: IMWG criteria met (active MM vs SMM vs MGUS)
  2. 2ENTRY
    Triggered from M-protein detection or CRAB workup (NCCN 2024 MM)
    inputs: cbc_with_diff
    advance: Suspicion confirmed
  3. 3CONTEXT
    Capture comorbidities, frailty (IMWG frailty score Palumbo JCO 2015), prior MGUS/SMM, transplant eligibility (NCCN 2024 MM)
    inputs: age, transplant_eligibility
    advance: Eligibility + frailty captured
  4. 4RED_FLAGS
    Cord compression; hyperviscosity; severe hypercalcemia; AKI from cast nephropathy; pathological fracture (NCCN 2024 MM)
    inputs: calcium, creatinine
    actions: workup.hyperviscosity
    advance: Emergencies stabilized
  5. 5INITIAL_WORKUP
    CBC + smear (rouleaux); CMP + Ca + albumin + LDH + B2M; SPEP + UPEP + SFL; whole-body imaging; quant Ig; viscosity if IgM/IgA (IMWG 2014 Rajkumar; NCCN 2024 MM)
    inputs: cbc_with_diff, creatinine, calcium, spep_upep_sfl, whole_body_imaging
    actions: panel.cbc, panel.renal, workup.mm_initial
    advance: Workup complete
  6. 6BRANCHING_WORKUP
    BM aspirate + biopsy + flow + cytogenetics + FISH del 17p, t(4;14), t(14;16), 1q gain; congo red if amyloid suspected (NCCN 2024 MM; IMWG 2014 Rajkumar)
    inputs: bm_biopsy
    advance: Stage + risk class assigned
  7. 7DIFFERENTIAL
    Bayesian progression continuum — MGUS (M-protein <3 g/dL, BM plasma cells <10%, no CRAB/SLiM; progression ~1%/yr) → SMM (≥3 g/dL or 10-60% PC, no CRAB/SLiM; progression ~10%/yr first 5 yr) → active MM (CRAB or SLiM biomarker: clonal PC ≥60%, FLC ratio ≥100, >1 focal MRI lesion). vs Waldenström (IgM + MYD88) / AL amyloid (Congo red) / POEMS / plasma cell leukemia — IMWG 2014 Rajkumar Lancet Oncol (PMID 25439696)
    advance: Diagnosis confirmed
  8. 8RISK_STRATIFICATION
    R-ISS staging B2M + albumin + LDH + cytogenetics (Palumbo JCO 2015); R2-ISS adds 1q (D Agostino Lancet Oncol 2022)
    advance: R-ISS stage documented
  9. 9TREATMENT
    Transplant-eligible: Dara-VRd induction (GRIFFIN — deeper sCR/MRD-negativity) → ASCT (DETERMINATION PMID 35660812: early ASCT median PFS ~67.5 vs 46.2 mo vs RVd-alone) → lenalidomide maintenance. Transplant-ineligible: Dara-Rd (MAIA Facon NEJM 2019 PMID 31141632: median PFS ~61.9 vs 34.4 mo, HR ~0.55 vs Rd); VRd alternative (SWOG S0777 Durie Lancet 2017 PMID 28017406: median OS ~75 vs 64 mo vs Rd). Relapse: anti-BCMA CAR-T cilta-cel (CARTITUDE-4 — PFS HR ~0.26 vs SoC) / ide-cel (KarMMa-3); bispecifics teclistamab (MajesTEC-1) (NCCN 2024 MM)
    inputs: transplant_eligibility
    advance: Induction started + supportive care plan
  10. 10DISPOSITION
    Heme/onc clinic; transplant referral; XRT for cord compression / lytic lesion; nephrology if cast nephropathy (NCCN 2024 MM)
    advance: Specialty referrals set
  11. 11MONITORING
    M-protein + SFL response IMWG criteria CR/VGPR/PR/MR (IMWG 2020 Kumar Lancet Oncol); CBC + CMP each cycle; bone surveillance; MRD assessment after induction (NCCN 2024 MM)
    inputs: spep_upep_sfl
    actions: panel.cbc, panel.renal
    advance: Response category assigned
  12. 12FOLLOWUP
    Maintenance lenalidomide (CALGB 100104 McCarthy NEJM 2012); relapse surveillance; second primary malignancy screening; vaccinations; bone health (NCCN 2024 MM)
    advance: Long-term plan documented