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Clinical calculator summary

Original 2015 IMWG R-ISS

Three-stage baseline prognostic system combining original ISS, LDH, and defined high-risk plasma-cell iFISH abnormalities.

Evidence-based context for fast calculator use

Purpose:
Describe original-cohort prognostic groups in newly diagnosed multiple myeloma.
Population:
Newly diagnosed multiple myeloma at baseline, with complete ISS laboratories, local LDH classification, and adequate iFISH testing.
Factors:
Beta-2 microglobulin, Albumin, LDH versus local ULN, del(17p), t(4;14), t(14;16)
Reference:
Palumbo et al. J Clin Oncol. 2015;33:2863-2869. doi:10.1200/JCO.2015.61.2267.
HomeR-ISS (Multiple Myeloma)
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R-ISS (Multiple Myeloma)

mg/L
g/dL

Clinical Context & Background

This calculator implements the original 2015 International Myeloma Working Group Revised International Staging System (R-ISS), not the later R2-ISS. It combines the original ISS classification with LDH relative to the local laboratory upper limit of normal and plasma-cell iFISH cytogenetics.
Use it only at baseline in newly diagnosed multiple myeloma. It is not intended for MGUS, smoldering myeloma, relapse, post-treatment restaging, or response assessment. Standard-risk cytogenetics should be selected only when del(17p), t(4;14), and t(14;16) were all adequately tested and absent. Historical cohort outcomes describe associations and are not individualized prognosis or treatment recommendations.
Primary Source EvidencePalumbo A, Avet-Loiseau H, Oliva S, et al. Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group. J Clin Oncol. 2015;33(26):2863-2869. doi:10.1200/JCO.2015.61.2267.
Formula Logic
ISS I: beta-2 microglobulin <3.5 mg/L and albumin >=3.5 g/dL; ISS III: beta-2 microglobulin >=5.5 mg/L; ISS II otherwise. R-ISS I: ISS I plus normal LDH plus standard-risk cytogenetics. R-ISS III: ISS III plus high LDH or high-risk cytogenetics. R-ISS II otherwise.

Reference Data

R-ISS StageExact criteriaOriginal 2015 cohort outcomes
Stage IISS I + normal LDH + standard-risk cytogenetics5-year OS 82%; 5-year PFS 55%; median OS not reached
Stage IINeither R-ISS I nor R-ISS III5-year OS 62%; 5-year PFS 36%; median OS 83 months
Stage IIIISS III + high LDH or high-risk cytogenetics5-year OS 40%; 5-year PFS 24%; median OS 43 months

Clinical Workflow

Use, Interpret, And Continue The Patient Pathway

Expand for workflow guidance, limitations, examples, and related next steps.

When To Use

  • Use at baseline in newly diagnosed multiple myeloma when all four classifications are available.
  • Use raw unrounded beta-2 microglobulin and albumin values.

How To Interpret

  • R-ISS I requires ISS I, normal LDH, and standard-risk cytogenetics.
  • R-ISS III requires ISS III plus either high LDH or high-risk cytogenetics; every other complete combination is R-ISS II.

What To Do Next

  • Integrate stage with current disease biology, patient factors, contemporary guidance, and specialist assessment.
  • Do not use historical cohort outcomes as individualized survival predictions or treatment recommendations.

Limitations

  • Not for MGUS, smoldering myeloma, relapse, post-treatment restaging, or response assessment.
  • Standard-risk cytogenetics requires adequate testing showing all three specified abnormalities absent.

Validated Population

Original 2015 IMWG cohort of newly diagnosed multiple myeloma trial participants.

Stage I example

B2M 3.49 mg/L, albumin 3.50 g/dL, normal LDH, and adequately tested standard-risk cytogenetics gives R-ISS Stage I.

Calculation verification history

Verified

  1. : Production browser revalidation

    • Three source-backed R-ISS cases passed through visible production controls across Stages I, II, and III.
    • The unsupported generic risk gauge was absent; no unexpected N/A, literal undefined value, stale control, or browser-console error was observed.
    Download latest production check (Excel)

    Case-level evidence is retained in validation/browser-revalidation/riss-Multiple-Myeloma-2026-08-03.json.

  2. : Local browser remediation

    • Valid R-ISS results now explicitly suppress the shared generic risk gauge so source-defined Stage I, II, and III remain the only displayed staging framework.
    • Ten source-backed cases passed through visible local browser controls across 11 submissions, covering ISS thresholds, LDH and cytogenetic branches, all three stages, required-field validation, and reset/repeat behavior.
    • The existing calculator-specific audit passed 292/292. Production status remains open until this commit is deployed and the public route is revalidated.

    Local case-level remediation evidence is retained in validation/browser-production/riss-Multiple-Myeloma.local-remediation.json.

  3. : Production browser validation

    • Ten source-backed cases were exercised on the public production route through visible browser controls; 10/10 case records passed their expected-versus-observed assertions across 11 visible submissions.
    • Overall browser status: failed-ui-and-console. medium: Every valid R-ISS result added a generic Low Risk / Intermediate / High Risk gauge although the source-defined classifications are R-ISS Stage I, II, and III and the calculator does not define those generic risk labels. | medium: Production emitted minified React error #418 during route loads/reloads used by this run.
    • Case-level inputs, expected and observed results, reset/repeat behavior, failure reproductions, and console evidence are retained in the production-browser evidence record.

    Case-level production evidence is retained in validation/browser-production/riss-Multiple-Myeloma.json.

  4. : Browser input adapter corrected and reverified

    • Accepted finite number values already normalized by the shared calculator form while retaining strict malformed-input rejection.
    • No equation, cutoff, unit, classification, or applicability rule changed; calculator-specific verification and the calculator-wide browser-input audit passed.

  5. : Full validation test

    • 292/292 independent source-rule, exact-boundary, malformed-input, UI, trace, immutability, and shared ISS-semantic parity checks passed.
    • Original 2015 IMWG R-ISS only; R2-ISS and the overall myeloma panel remain unverified/In review.

  6. : Calculation and input-contract correction

    • Removed favorable defaults and permissive coercion; added exact complete positive laboratory inputs, explicit LDH and adequately tested cytogenetic classifications, and exact 3.5/5.5 ISS boundaries.
    • Added source-exact trace, baseline newly diagnosed scope warnings, and historical OS/PFS wording without individualized prognosis or treatment advice.

Verification confirms the calculator implementation against the cited model; it is not independent clinical validation, regulatory approval, or medical advice.

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Frequently Asked Questions

Is R-ISS the same as R2-ISS?

No. This page implements the original 2015 R-ISS. R2-ISS is a later, separate weighted system.

How is beta-2 microglobulin exactly 5.5 mg/L handled?

A value of 5.5 mg/L is ISS Stage III. It becomes R-ISS Stage III only when LDH is high or high-risk cytogenetics is present; otherwise it is R-ISS Stage II.

What does normal LDH mean?

LDH is normal/not high when it is not above the reporting laboratory upper limit of normal. Equality to the ULN is not high.

Evidence-based oncology decision support. Verify with clinical guidelines.