Statistical & Clinical Analysis
R-ISS Multiple Myeloma Staging Formula: IMWG Beta-2-Microglobulin, Albumin, FISH & LDH
Stage newly diagnosed Multiple Myeloma using Antonio Palumbo’s IMWG Revised International Staging System (R-ISS I, II, III) combining Greipp’s ISS (B2M & Albumin) with high-risk interphase FISH [del(17p), t(4;14), t(14;16)] and serum LDH.
Integrating tumor burden (B2M + Albumin) with tumor biology (interphase FISH + LDH) in IMWG R-ISS!
Philip R. Greipp’s 2005 International Staging System (ISS) staged Multiple Myeloma purely from serum Beta-2-Microglobulin (B2M: < 3.5 mg/L and Albumin >= 3.5 g/dL -> ISS I; B2M >= 5.5 mg/L -> ISS III; neither -> ISS II). Antonio Palumbo et al. (2015, Journal of Clinical Oncology — International Myeloma Working Group, 3,060 patients) refined ISS into R-ISS by adding chromosomal biology (High-Risk iFISH = del(17p), t(4;14), or t(14;16)) and elevated serum LDH (> ULN)!
Under IMWG R-ISS: R-ISS Stage I requires ALL THREE of ISS I (B2M < 3.5 mg/L AND Albumin >= 3.5 g/dL), Standard-Risk FISH (0), AND Normal LDH (0) (5-yr OS ~82%); R-ISS Stage III requires ISS III (B2M >= 5.5 mg/L) PLUS EITHER High-Risk FISH (1) OR High LDH (1) (5-yr OS ~40%); and EVERY other combination (including ISS I with del(17p), or ISS III with standard FISH and normal LDH!) maps cleanly to R-ISS Stage II (5-yr OS ~62%)!
| B2M (mg/L) & Albumin (g/dL) | High-Risk FISH / High LDH | Greipp ISS (2005) | Palumbo IMWG R-ISS (2015) |
|---|---|---|---|
| B2M = 6.4 (>= 5.5), Alb = 3.1 | del(17p) Positive (FISH = 1) | ISS Stage III | R-ISS Stage III (High-Risk Biology + Burden) |
| B2M = 2.6 (< 3.5), Alb = 3.9 (>= 3.5) | Standard FISH (0) & Normal LDH (0) | ISS Stage I | R-ISS Stage I (Favorable Prognosis) |
| B2M = 2.6 (< 3.5), Alb = 3.9 (>= 3.5) | t(4;14) Positive (FISH = 1) | ISS Stage I | Upstaged to R-ISS Stage II! |
IMWG Revised International Staging System (R-ISS Stage I, II, III) Formula
Evaluates exact Palumbo 2015 IMWG logic from Beta-2-Microglobulin (B2, mg/L), Serum Albumin (B3, g/dL), High-Risk FISH flag (B4, 0/1), and Elevated LDH > ULN flag (B5, 0/1).
=IF(OR(B2 <= 0, B3 <= 0, B4 < 0, B4 > 1, B5 < 0, B5 > 1), "Invalid Myeloma Staging Inputs", IF(AND(B2 < 3.5, B3 >= 3.5, B4 = 0, B5 = 0), "R-ISS Stage I (ISS I + Standard FISH + Normal LDH)", IF(AND(B2 >= 5.5, OR(B4 = 1, B5 = 1)), "R-ISS Stage III (ISS III + High-Risk FISH or Elevated LDH)", "R-ISS Stage II (Intermediate — Not Meeting Stage I or III)")))Underlying 2005 Greipp ISS Stage (I, II, or III from B2M & Albumin Alone)
Computes the base 2-biomarker ISS stage before FISH/LDH biological reclassification.
=IF(OR(B2 <= 0, B3 <= 0, B4 < 0, B4 > 1, B5 < 0, B5 > 1), "Invalid Myeloma Staging Inputs", IF(B2 >= 5.5, "ISS Stage III", IF(AND(B2 < 3.5, B3 >= 3.5), "ISS Stage I", "ISS Stage II")))Try the example
Use the original values or change them to test your understanding.