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Multiple Myeloma Prognosis

Inter-laboratory comparison of beta-2 microglobulin methods: impact of assay variation on multiple myeloma staging. Pasquale Fedele, Kay- Weng Choy, James Doery , Jake Shortt , George Grigoriadis, Zhong Lu. Multiple Myeloma Prognosis.

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Multiple Myeloma Prognosis

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  1. Inter-laboratory comparison of beta-2 microglobulin methods: impact of assay variation on multiple myeloma staging Pasquale Fedele, Kay-WengChoy, James Doery, Jake Shortt, George Grigoriadis, Zhong Lu.

  2. Multiple Myeloma Prognosis

  3. 10,750 previously untreated symptomatic myeloma patients from 17 institutions, including sites in North America, Europe and Asia. • Data collected from 1981 through 2002.

  4. Serum β2M, albumin, platelet count, creatinine and age emerged as powerful predictors of survival • Combination of serum β2M and albumin provided the simplest, most powerful and reproducible three stage classification Greipp et al J Clin Oncol 2005 23(15): 3412 - 3420

  5. Subsequent findings • Discordant albumin results previously reported Snozek et al Clin Chem. 2007; 53(6): 1099-103 Quick et al Clin Chem. 2009; 55(3): 594-6. Review of 496 patients: ISS staging discordant between BCG vs SPEP in 69 patients. No statistically significant difference in survival compared with “true” stage I and II patients. Rajkumar et al J Clin Oncol 2008

  6. β2M Analysis • Several methods of β2M detection: • Nephelometry • Turbidimetry • Chemiluminescence immunoassay • Enzyme immunoassay • Correlation previously thought to be satisfactory • Cf: Radioimmunoassay – poor correlation with other methods. Tichy et al Neoplasma 2006 53(6): 492 - 494

  7. RCPA Chemical Pathology QAP • β2M (Tumour Marker Program Cycle 39)

  8. Aim • Investigate the inter-method/inter-laboratory variation of β2M on human samples. • Determine the implications this has on ISS prognostic scores.

  9. Methods: stability of β2M analyte • 10 samples spun down, tested and simultaneously aliquoted for storage at: • Room temp • Refrigerated at 4°C • Frozen at -20°C and later thawed at 37°C • Frozen at -20°C and later thawed at room temp • Results stable after freeze/thawing

  10. Methods: interlaboratory variability • 21 patient serum samples sent frozen to 4 labs Lab1: Nephelometric (Immage 800) Lab3: Turbidimetric (Roche Cobas c502a) http://www.beckmancoulter.com http://www.roche.com (actually Cobas c602) Lab4: Tubidimetric (Abbott Architect c16200) http://www.abbottdiagnostics.de (Architect c16200) Lab2: Chemiluminescence Immunoassay (Immunlite 2000) http://www.healthcare.siemens.com (Immulite 2000 XPi)

  11. Results Lab1: Nephelometric (Immage) Lab4: Turbidimetric (Architect) 0.51 (-9.3%) (0.29-0.73 p<0.001) Lab3: Turbidimetric (Cobas) 1.09 (-20.1%) (0.78-1.41 p<0.001) Lab2: CLIA (Immulite) 1.55 (-28.5%) (1.02-2.09 p<0.001)

  12. Results – compare with QAP Lab3 & Lab4 Lab2 Lab1

  13. Results – ISS scores ISS scores concordant by all 4 labs in only 12/21 (57%) patients Initial ISS survival data (Greipp 2005)

  14. Discussion – Why is this important • Significant implications on the validity of the ISS for individual patients. • Illustrates difficulties in applying any test or staging system in the “real world”. • Implications for clinical trials: • Patient stratification (ensure same method for β2M) • Comparison between trials.

  15. Discussion • Harmonisation of β2M methods is needed. • Currently no recognised international reference material available. • β2M method in the initial ISS study not reported. • involved 17 sites across 3 continents – unlikely methodology was concordant across all institutions.

  16. Conclusion • Re-validation of the ISS system required: • Difficulties in standardisation of β2M methods. • Myeloma treatment and supportive care measures have advanced significantly since the original ISS study. • It seems appropriate that we re-evaluate the prognostic information we give to our patients.

  17. Acknowledgements • Monash Medical Centre • Kay-Weng Choy • Zhong Lu • James Doery • George Grigoriadis • Jake Shortt • George Streitberg • Healthscope • MiretteSaad • Alfred Hospital • Christina Trambas • RCPA Chemical Pathology QAP

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