Inter-laboratory comparison of beta-2 microglobulin and albumin methods: impact of assay variation on multiple myeloma staging

Myeloma prognostication is largely defined by the International Staging System (ISS)1 using serum beta-2 microglobulin ((32M) and albumin results. Local EQA (RCPA-QAP) data showed substantial, method-dependant variations in (β2M results). We determined the variability of different (32 M methods using patient samples, and whether this influences ISS prognostic scores. (β2M stability after freeze-thawing was established first. Specimens (n = 21) were then sent frozen to three laboratories using different methods for (β2M [lab 1, nephelometric; lab 2, chemiluminescent immunoassay (CLIA); and lab 3, enzyme immunoassay (EIA)]. All laboratories use the same albumin method (bromocresol purple). Results were assessed using Passing-Bablok regression and concordance for ISS scores. Lab 1 produced (β2M results consistently higher than other laboratories ((β2MLab2 = 0.79×(β2MLabl-0.09; (β2MLab3 = 0.70×(β2MLabl+0.17). Only 12 of 21 (57%) of the ISS prognostic scores were concordant by all three laboratories. Compared to Lab1, ISS scores were classified one stage lower in five and seven patients by Lab 2 and Lab 3, respectively. One additional patient was classified as stage 3 by Lab 1 but stage 1 by Lab 3. Albumin methods aligned well and had minimal impact on ISS score. Results from different (β2M methods are highly variable and harmonisation is required. This study has important implications on the validity of ISS staging for myeloma.