多发性骨髓瘤中的轻链逃逸现象-目前使用游离轻链监控病人的最大病人数量

‘Light-chain escape-multiple myeloma’—an escape phenomenon from plateau phase: report of the largest patient series using LC-monitoring (MKG487)

A. Kühnemund, P. Liebisch, K. Bauchmüller, A. zur Hausen, H. Veelken, R. Wäsch, M. Engelhardt

Journal of Cancer Research & Clinical Oncology, 18th September 2008

Background

More intensive and novel therapy options in Multiple Myeloma (MM) have the potential to improve treatment outcome. However disease evolution induced with long disease duration and extensive pre-treatment has resulted in a change in the biological behaviour of MM and novel manifestations of relapsed disease, eg. extramedullary disease or a shift in secretion from intact immunoglobulin to free light chain (FLCs) only.

This report highlights the importance of early detection of light chain escape (LCE) to prevent unnecessary complications and also states that monitoring patients by intact immunoglobulin levels is not sufficient. The article calls for all patients to be serially monitored with serum FLCs.

Method

This report studied the prevalence of light chain escape within 407 MM patients treated between 2004 and 2007. For the 10 patients who relapsed with LCE-MM, detailed analysis of patient characteristics, serum FLC changes, therapy responses and mode and speed of progression was performed.

Results

This is the largest published case series to date. The patients’ MM appeared stable as judged by conventional monitoring of intact immunoglobulin levels but they developed severe organ dysfunction as a consequence of initially undetected light chain progression. Clinical symptoms of LCE were deterioration of patients’ general condition in 10/10 cases, renal impairment in 5/10, reoccurrence of severe bone pain in 4/10 and anaemia in 3/10. Relapse of disease with LCE was difficult to treat and was usually associated with only a short period of remission. 6/10 patients were deceased after a median time of 11 months following LCE. The LCE-MM prevalence within 407 patients between 2004 - 2007 was 2.46%. Conclusion

The authors conclude that electrophoresis and quantitative immunoglobulin measurement were unable to detect disease progression with LCE. Serum FLCs were shown to be reliable markers and the authors suggest that serum FLCs should be included in the follow-up of patients rather than immunoglobulin levels alone.

“We agree, nevertheless, that LCE-MM is important to identify, especially in the era of more intensive and biological therapy options and may need more cunning treatment options.”

“With this to date largest documented series of an important mode of relapse, we demonstrate that sFLCs are reliable markers of disease progression. Early detection of LCE-MM should prevent the occurrence of unnecessary disease complications, such as renal impairment or symptomatic bone lesions in patients deemed to be progression-free by standard assessment of intact Ig kinetics.

“In summary our report demonstrates that the capacity of myeloma cells to produce intact Ig declines during the disease course and that it should be routine practice to check different aspects of the disease activity in the follow-up rather than Ig levels alone, namely SFLCs…..”

DTP 306