Prognostic Significance of Isolated Beta 2-Microglobulin Elevation in Thai Multiple Myeloma: Impact of Renal Function Assessment

Abstract

Background: The 2024 International Myeloma Society–International Myeloma Working Group consensus classifies isolated elevated β₂-microglobulin (β2M) with normal serum creatinine (SCr) as high-risk multiple myeloma (MM). However, creatinine-based renal definitions may be inaccurate in Asian populations with lower muscle mass. We aimed to evaluate the prognostic impact of isolated elevated β2M on overall survival (OS) using SCr- and Cockcroft–Gault-derived creatinine clearance (CrCl)-based definitions.

Methods: This retrospective study included newly diagnosed MM patients (2006–2023). Patients were classified as group A (β2M < 5.5 mg/L), group B (β2M ≥ 5.5 mg/L, SCr < 1.2 mg/dL), or group C (β2M ≥ 5.5 mg/L, SCr ≥ 1.2 mg/dL). In secondary analyses, renal function was redefined using CrCl (≥ 60 mL/min).

Results: Among 250 patients (mean age 61.0 ± 12.1 years; 62.0% male), 34.4% underwent autologous stem cell transplantation. Groups A, B, and C included 109 (43.6%), 29 (11.6%), and 112 (44.8%) patients, respectively. At a median follow-up of 4.55 years, 4-year OS for groups A, B, and C was 79.8%, 71.6%, and 60.0% (P = 0.015). Group B did not demonstrate significantly inferior OS compared with group A (adjusted hazard ratio (aHR), 1.51; 95% confidence interval (CI), 0.70–3.24), whereas group C had significantly worse OS (aHR, 1.79; 95% CI, 1.11–2.86). When renal function was defined by CrCl, reclassified group B (n = 19) showed significantly inferior OS (aHR, 2.61; 95% CI, 1.17–5.86).

Conclusions: Isolated β2M elevation showed a trend toward inferior OS using the SCr-based definition. CrCl-based reclassification appeared to improve prognostic stratification by identifying occult renal impairment not detected by SCr alone. These findings require validation in larger studies.