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Mieloma múltiplo com R-ISS estágio 3 — ISS-3 (β2M ≥5,5) PLUS LDH acima de ULN PLUS alto risco...

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IDRF-R-ISS-3-HIGH-RISK
TipoSinal de alerta
Estadoreviewed 2026-04-27 | pending_clinical_signoff
DoençasDIS-MM
FontesSRC-ESMO-MM-2023 SRC-NCCN-MM-2025

Origem da bandeira vermelha

DefiniçãoMultiple myeloma with R-ISS stage 3 — ISS-3 (β2M ≥5.5) PLUS LDH above ULN PLUS high-risk cytogenetics by FISH (any of t(4;14), t(14;16), del(17p)) — most aggressive presentation; supports four-drug D-VRd induction + ASCT (eligible) or D-Rd intensification (unfit) + maintenance
Direcção clínicaintensificar
Categoriarisco-ponto
Algoritmo de deslocamentosALGO-MM-1L

Lógica de Desencadeamento

{
  "all_of": [
    {
      "comparator": ">=",
      "finding": "beta2_microglobulin_mg_per_l",
      "threshold": 5.5
    },
    {
      "finding": "ldh_above_uln",
      "value": true
    },
    {
      "any_of": [
        {
          "finding": "mm_high_risk_cytogenetics",
          "value": true
        },
        {
          "finding": "fish_t_4_14",
          "value": true
        },
        {
          "finding": "fish_t_14_16",
          "value": true
        },
        {
          "finding": "fish_del_17p",
          "value": true
        },
        {
          "finding": "tp53_deletion",
          "value": true
        }
      ]
    }
  ],
  "type": "composite_score"
}

Notas

R-ISS (Palumbo et al., JCO 2015) refined ISS by adding LDH and FISH cytogenetics: R-ISS-3 = ISS-3 + LDH-high + high-risk FISH. R-ISS-3 median OS ~43 mo pre-daratumumab; modern PERSEUS / IsKia / GRIFFIN show D-VRd benefits across risk groups but absolute outcomes in R-ISS-3 remain inferior — argues for tandem ASCT consideration (StaMINA / EMN02) and aggressive maintenance (lenalidomide +/- daratumumab + ixazomib in selected protocols). Severity `critical` for conflict resolution: this should win over standard de-escalation flags. Co-fires with biomarker-actionability flags for individual cytogenetic hits.

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Algoritmos

Sinal de alerta