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heme.multiple-myeloma.chronic.v1PRODUCTION
heme.multiple-myeloma.chronic.v1

Multiple Myeloma (initial diagnosis + chronic management)

oncologychronicsubacuteadult
Hard-required inputs
0 / 7
Care setting:

Encounter flow

12/12 authored

Canonical 12-phase frame with authored status for this dossier.

Current phase

Frame

Detailed

Apply IMWG 2014 criteria — CRAB or SLiM biomarkers: >=60% PCs, FLC ratio >=100, MRI >=1 focal lesion (Rajkumar Lancet Oncol 2014)

Inputs
3
Actions
0
Advance rule
Set
Advance when

IMWG criteria met (active MM vs SMM vs MGUS)

Patient inputs (8)

Transplant eligibility cutoff + dose adjustments (NCCN 2024 MM; IMWG 2020 Rajkumar)

Determines D-VRD eligible vs D-Rd ineligible (NCCN 2024 MM; Richardson NEJM 2022 DETERMINATION)

Anemia (rouleaux), leukopenia, thrombocytopenia; CRAB criteria (IMWG 2014 Rajkumar Lancet Oncol)

CRAB renal criterion Cr >2 or eGFR <40; cast nephropathy (IMWG 2014 Rajkumar Lancet Oncol)

CRAB hypercalcemia >11 mg/dL or >1 mg above upper limit (IMWG 2014 Rajkumar Lancet Oncol)

M-protein quantification + Bence Jones; serum free light chain ratio (IMWG 2014 Rajkumar Lancet Oncol; NCCN 2024 MM)

Whole-body low-dose CT or MRI or PET/CT for lytic lesions CRAB B (IMWG 2014 Rajkumar Lancet Oncol; NCCN 2024 MM)

Plasma cell percentage; cytogenetics + FISH for risk stratification (IMWG 2014 Rajkumar Lancet Oncol; NCCN 2024 MM)

* = hard-required. Engine cannot meaningfully run until these are filled.

Severity triggers (7)

7 need judgement
  • informationallife_threateningspinal_cord_compression
    Back pain + new neurologic deficit (weakness, sensory, sphincter) (NCCN 2024 MM)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateninghyperviscosity
    IgM/IgA spike + visual blurring / neurologic / bleeding triad (NCCN 2024 MM)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverehypercalcemia_of_malignancy
    Serum Ca >12 with symptoms or Ca >14 (NCCN 2024 MM)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverecast_nephropathy_aki
    AKI + Bence Jones proteinuria + bland sediment (NCCN 2024 MM)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverecrs_after_car_t
    Fever + hypotension + hypoxia after CAR-T (ASTCT 2019 Lee)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereicans
    Encephalopathy / aphasia / seizure after CAR-T (ASTCT 2019 Lee)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatetls_in_high_burden_mm
    Initiation of cytoreductive therapy in high tumor burden MM (NCCN 2024 MM)
    Trigger could not be auto-evaluated — needs clinician judgement.

Workflow calculators

Run this disease's risk and dosing calculators inline.

RISK_STRATIFICATIONoptionalDrives severity classification
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Recommended regimen

MM treatment by transplant eligibility (NCCN 2024 MM + IMWG 2020 Rajkumar + GRIFFIN Voorhees Blood 2020 + MAIA Facon NEJM 2019)
axis: mm_induction_eligibility_drivenstep transplant_eligible_induction - Transplant-eligible — D-VRD induction (GRIFFIN Voorhees Blood 2020) → ASCT → lenalidomide maintenance
Selected step "Transplant-eligible — D-VRD induction (GRIFFIN Voorhees Blood 2020) → ASCT → lenalidomide maintenance" — Age <70-75 + good performance + adequate organ function + transplant accepted (NCCN 2024 MM; IMWG 2020 Rajkumar)
  • daratumumab
    first line
    anti_CD38_mAb
    16 mg/kg IV (or 1800 mg SC) weekly × 8 then q2w × 8 then q4w • IV/SC • weekly → q2w → q4w
    triggers: transplant_eligible
    GRIFFIN Voorhees Blood 2020 — added benefit to VRD; SC formulation daratumumab-hyaluronidase (NCCN 2024 MM)
    rxcui 1721947
  • bortezomib
    first line
    proteasome_inhibitor
    1.3 mg/m² SC • SC • days 1, 4, 8, 11 of 21-day cycle
    triggers: mm_induction
    GRIFFIN Voorhees Blood 2020 backbone; SC route reduces neuropathy (Moreau Lancet Oncol 2011)
    rxcui 358258
  • lenalidomide
    first line
    IMiD
    25 mg PO daily days 1-14 of 21-day cycle • PO • daily × 14 of 21
    triggers: mm_induction, no_severe_renal
    GRIFFIN Voorhees Blood 2020; renal-dose adjust if eGFR <60 (NCCN 2024 MM)
    rxcui 342369
  • dexamethasone
    first line
    corticosteroid
    40 mg PO weekly (20 mg if >75) • PO • weekly
    triggers: mm_induction
    GRIFFIN Voorhees Blood 2020; 20 mg if age >75 (NCCN 2024 MM)
    rxcui 3264

outpatient playbook — drug actions (5)

  1. 1. D-VRD induction
    Per axis • IV/SC/PO • q21d x 4-6 cycles
    trigger: Transplant-eligible per NCCN 2024 MM
    GRIFFIN Voorhees Blood 2020; NCCN 2024 MM
  2. 2. D-Rd induction
    Per axis • IV/SC/PO • q28d
    trigger: Transplant-ineligible per NCCN 2024 MM
    MAIA Facon NEJM 2019; NCCN 2024 MM
  3. 3. lenalidomide maintenance
    10 mg PO daily • PO • daily
    trigger: Post-ASCT per NCCN 2024 MM
    CALGB 100104 McCarthy NEJM 2012; NCCN 2024 MM
  4. 4. zoledronic acid
    4 mg IV q4 weeks • IV • q4w
    trigger: Lytic lesions or osteopenia (NCCN 2024 MM)
    NCCN 2024 MM
  5. 5. aspirin VTE prophylaxis
    81-325 mg PO daily • PO • daily
    trigger: IMiD use (NCCN 2024 MM)
    IMWG VTE prophylaxis Palumbo JCO 2008; NCCN 2024 MM

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: M-protein on SPEP/UPEP/serum free light chain (IMWG 2014 Rajkumar Lancet Oncol); CRAB: hyperCalcemia / Renal failure / Anemia / Bone lesion (IMWG 2014 Rajkumar Lancet Oncol); Bone pain / pathological fracture (NCCN 2024 MM).

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Multiple Myeloma (initial diagnosis + chronic management)** (heme.multiple-myeloma.chronic.v1).
Phenotype framing: 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)
Scope: Apply IMWG 2014 criteria — CRAB or SLiM biomarkers: >=60% PCs, FLC ratio >=100, MRI >=1 focal lesion (Rajkumar Lancet Oncol 2014)

No severity triggers fired against current inputs.

Plan

Regimen axis: **MM treatment by transplant eligibility (NCCN 2024 MM + IMWG 2020 Rajkumar + GRIFFIN Voorhees Blood 2020 + MAIA Facon NEJM 2019)** — step "Transplant-eligible — D-VRD induction (GRIFFIN Voorhees Blood 2020) → ASCT → lenalidomide maintenance".
1. daratumumab 16 mg/kg IV (or 1800 mg SC) weekly × 8 then q2w × 8 then q4w IV/SC weekly → q2w → q4w (anti_CD38_mAb, first line) — GRIFFIN Voorhees Blood 2020 — added benefit to VRD; SC formulation daratumumab-hyaluronidase (NCCN 2024 MM)
2. bortezomib 1.3 mg/m² SC SC days 1, 4, 8, 11 of 21-day cycle (proteasome_inhibitor, first line) — GRIFFIN Voorhees Blood 2020 backbone; SC route reduces neuropathy (Moreau Lancet Oncol 2011)
3. lenalidomide 25 mg PO daily days 1-14 of 21-day cycle PO daily × 14 of 21 (IMiD, first line) — GRIFFIN Voorhees Blood 2020; renal-dose adjust if eGFR <60 (NCCN 2024 MM)
4. dexamethasone 40 mg PO weekly (20 mg if >75) PO weekly (corticosteroid, first line) — GRIFFIN Voorhees Blood 2020; 20 mg if age >75 (NCCN 2024 MM)

Setting playbook (outpatient) — Initiate and maintain induction/maintenance per NCCN 2024 MM, manage supportive care, monitor MRD per IMWG 2020 Kumar Lancet Oncol, and detect complications
5. D-VRD induction Per axis IV/SC/PO q21d x 4-6 cycles — Transplant-eligible per NCCN 2024 MM (GRIFFIN Voorhees Blood 2020; NCCN 2024 MM)
6. D-Rd induction Per axis IV/SC/PO q28d — Transplant-ineligible per NCCN 2024 MM (MAIA Facon NEJM 2019; NCCN 2024 MM)
7. lenalidomide maintenance 10 mg PO daily PO daily — Post-ASCT per NCCN 2024 MM (CALGB 100104 McCarthy NEJM 2012; NCCN 2024 MM)
8. zoledronic acid 4 mg IV q4 weeks IV q4w — Lytic lesions or osteopenia (NCCN 2024 MM) (NCCN 2024 MM)
9. aspirin VTE prophylaxis 81-325 mg PO daily PO daily — IMiD use (NCCN 2024 MM) (IMWG VTE prophylaxis Palumbo JCO 2008; NCCN 2024 MM)

Non-pharmacologic actions:
- Vaccinations (pneumococcal, flu, COVID, RSV, HBV) (NCCN 2024 MM)
- Dental clearance before bisphosphonate (NCCN 2024 MM)
- Bone health Ca + vit D (NCCN 2024 MM)
- Education on neuropathy/fatigue (NCCN 2024 MM)

AVOID / contraindication checks:
- Bortezomib neuropathy monitor and SC route (NCCN 2024 MM; Moreau Lancet Oncol 2011)
- Lenalidomide VTE prophylaxis (IMWG 2014 Palumbo JCO; NCCN 2024 MM)
- Lenalidomide renal dose if egfr lt 60 (NCCN 2024 MM)
- Dara infusion reaction premedicate (NCCN 2024 MM)
- Bisphosphonate renal dose (NCCN 2024 MM)
- Bisphosphonate ONJ dental clearance (NCCN 2024 MM)
- CAR T CRS ICANS monitoring (NCCN 2024 MM; ASTCT 2019 Lee)

Monitoring

Regimen monitoring:
- M-protein + SFL each cycle (IMWG 2020 Kumar Lancet Oncol; NCCN 2024 MM)
- CBC + CMP each cycle (NCCN 2024 MM)
- Bone surveillance annually (NCCN 2024 MM)
- MRD assessment after induction + maintenance (IMWG 2020 Kumar Lancet Oncol; NCCN 2024 MM)
- Echo before bortezomib/carfilzomib (NCCN 2024 MM)
- eGFR each cycle for renal dose adjustment (NCCN 2024 MM)
- IVIG monthly if hypogammaglobulinemia IgG <400 (NCCN 2024 MM)

Setting (outpatient) monitoring:
- Per cycle labs (NCCN 2024 MM)
- IMWG response criteria (IMWG 2020 Kumar Lancet Oncol)
- Neuropathy assessment q visit (NCCN 2024 MM)
- MRD post-induction (IMWG 2020 Kumar Lancet Oncol; NCCN 2024 MM)

Follow-up plan: Maintenance lenalidomide (CALGB 100104 McCarthy NEJM 2012); relapse surveillance; second primary malignancy screening; vaccinations; bone health (NCCN 2024 MM)
- Close-out criterion: Long-term plan documented

Monitoring phase: 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)

Disposition

Current setting: outpatient — Initiate and maintain induction/maintenance per NCCN 2024 MM, manage supportive care, monitor MRD per IMWG 2020 Kumar Lancet Oncol, and detect complications

Disposition criteria:
- Continue induction if responding (IMWG 2020 Kumar Lancet Oncol)
- ASCT referral after 4-6 cycles (NCCN 2024 MM; Richardson NEJM 2022 DETERMINATION)
- Transition to maintenance at remission (NCCN 2024 MM)

Escalation triggers (move to higher acuity):
- Hypercalcemia → ED + IV fluids + bisphosphonate (NCCN 2024 MM)
- New back pain + neurologic deficit → STAT MRI for cord compression (NCCN 2024 MM)
- AKI → cast nephropathy workup (NCCN 2024 MM)
- Severe neuropathy on bortezomib → switch to SC or hold (Moreau Lancet Oncol 2011; NCCN 2024 MM)

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] Back pain + new neurologic deficit (weakness, sensory, sphincter) (NCCN 2024 MM)
- [LIFE_THREATENING] IgM/IgA spike + visual blurring / neurologic / bleeding triad (NCCN 2024 MM)
- [SEVERE] Serum Ca >12 with symptoms or Ca >14 (NCCN 2024 MM)

Citations

- NCCN 2024 Multiple Myeloma + IMWG 2014 Diagnostic Criteria (Rajkumar Lancet Oncol 2014) + IMWG 2020 Response Criteria (Kumar Lancet Oncol) + GRIFFIN (Voorhees Blood 2020) + MAIA (Facon NEJM 2019) + DETERMINATION (Richardson NEJM 2022) + SWOG S0777 (Durie Lancet 2017) + KRd (Stewart NEJM 2015) + CARTITUDE-4 (San-Miguel NEJM 2023) [PMID:25439696](https://pubmed.ncbi.nlm.nih.gov/25439696/)
- Cited evidence (PMID 31141632) [PMID:31141632](https://pubmed.ncbi.nlm.nih.gov/31141632/)
- Cited evidence (PMID 28017406) [PMID:28017406](https://pubmed.ncbi.nlm.nih.gov/28017406/)
- Cited evidence (PMID 25482145) [PMID:25482145](https://pubmed.ncbi.nlm.nih.gov/25482145/)
- Cited evidence (PMID 35660812) [PMID:35660812](https://pubmed.ncbi.nlm.nih.gov/35660812/)

Last reconciled with current guidelines: 2026-05-22.
References
  • NCCN 2024 Multiple Myeloma + IMWG 2014 Diagnostic Criteria (Rajkumar Lancet Oncol 2014) + IMWG 2020 Response Criteria (Kumar Lancet Oncol) + GRIFFIN (Voorhees Blood 2020) + MAIA (Facon NEJM 2019) + DETERMINATION (Richardson NEJM 2022) + SWOG S0777 (Durie Lancet 2017) + KRd (Stewart NEJM 2015) + CARTITUDE-4 (San-Miguel NEJM 2023) — PMID:25439696
  • Cited evidence (PMID 31141632) — PMID:31141632
  • Cited evidence (PMID 28017406) — PMID:28017406
  • Cited evidence (PMID 25482145) — PMID:25482145
  • Cited evidence (PMID 35660812) — PMID:35660812