Abstract
Purpose
More intensive and novel therapy options in multiple myeloma (MM) hold the promise to improve treatment outcome. However, disease evolution, induced with long disease duration and extensive pretreatment, has resulted in changes in the biological behaviour of MM and unusual relapse emergence, such as of extramedullary (EM) disease or a shift in secretion from intact immunoglobulin (Ig) to free-light chains (FLCs) only.
Methods
We studied ten patients since 2004, thoroughly assessed relevant patient characteristics, prominent similarities, SFLC-changes, therapy response, mode and speed of progression, and the incidence of light-chain escape (LCE)-MM within our entire myeloma patient cohort. Serum FLCs (SFLCs) were determined via Freelite-assay (Dade-Behringer Nephelometer).
Results
This report summarizes the to date largest series of ten patients, whose MM appeared stable, as judged by conventional monitoring of intact Ig levels, but developed severe organ dysfunction as a consequence of initially undetected LC-progression. Median number of anti-MM cycles before LCE occurrence was six, including autologous and/or allogeneic stem cell transplants and novel drugs, predominantly thalidomide, in 4/10. Classic diagnostics, such as electrophoresis and quantitative Ig measurement proved futile to detect LC-progression, whereas SFLCs were reliable markers. The LCE-MM prevalence within 407 MM patients treated in our institution between 2004 and 2007 was 2.46%.
Conclusions
Our report suggests that early detection of LCE-MM by means of serial SFLC measurements may prevent unnecessary complications, allows to detect unusual relapse manifestations in the era of intensive and biological therapy options and possibly also permits to improve treatment results in LCE-MM.
This is a preview of subscription content, log in via an institution to check access.
References
Avet-Loiseau H, Brigaudeau C, Morineau N, Talmant P, Lai JL, Daviet A et al (1999) High incidence of cryptic translocations involving the Ig heavy chain gene in multiple myeloma, as shown by fluorescence in situ hybridization. Genes Chromosomes Cancer 24(1):9–15. doi : 10.1002/(SICI)1098-2264(199901)24:1<9::AID-GCC2>3.0.CO;2-K
Coriu D, Weaver K, Schell M, Eulitz M, Murphy CL, Weiss DT et al (2004) A molecular basis for nonsecretory myeloma. Blood 104(3):829–831. doi:10.1182/blood-2004-02-0477
Dawson MA, Patil S, Spencer A (2007) Extramedullary relapse of multiple myeloma associated with a shift in secretion from intact immunoglobulin to light chains. Haematologica 92(1):143–144. doi:10.3324/haematol.10297
Denz U, Haas PS, Wasch R, Einsele H, Engelhardt M (2006) State of the art therapy in multiple myeloma and future perspectives. Eur J Cancer 42(11):1591–1600. doi:10.1016/j.ejca.2005.11.040
Engelhardt M, Mertelsmann R (2006) 160 years of multiple myeloma: progress and challenges. Eur J Cancer 42(11):1507–1509. doi:10.1016/j.ejca.2006.05.003
Haas PS, Bauchmuller K, Kuhnemund A, Finke J, Ihorst G, Engelhardt M (2006) Efficacy of diverse high-dose regimens followed by autologous peripheral blood stem cell transplantation in consecutive multiple myeloma patients: a single-centre analysis over a 12-year period. Ann Hematol 85(3):191–193. doi:10.1007/s00277-005-0040-x
Haas PS, Denz U, Ihorst G, Engelhardt M (2008) Thalidomide in consecutive multiple myeloma patients: single-center analysis on practical aspects, efficacy, side effects and prognostic factors with lower thalidomide doses. Eur J Haematol 80(4):303–309
Joshua DE, Gibson J, Brown RD (1994) Mechanisms of the escape phase of myeloma. Blood Rev 8(1):13–20. doi:10.1016/0268-960X(94)90003-5
Kleber M, Cybulla M, Bauchmuller K, Ihorst G, Koch B, Engelhardt M (2007) Monitoring of renal function in cancer patients: an ongoing challenge for clinical practice. Ann Oncol 18(5):950–958. doi:10.1093/annonc/mdm055
Kropff M, Bisping G, Schuck E, Liebisch P, Lang N, Hentrich M et al (2007) Bortezomib in combination with intermediate-dose dexamethasone and continuous low-dose oral cyclophosphamide for relapsed multiple myeloma. Br J Haematol 138(3):330–337. doi:10.1111/j.1365-2141.2007.06656.x
Kuipers J, Vaandrager JW, Weghuis DO, Pearson PL, Scheres J, Lokhorst HM et al (1999) Fluorescence in situ hybridization analysis shows the frequent occurrence of 14q32.3 rearrangements with involvement of immunoglobulin switch regions in myeloma cell lines. Cancer Genet Cytogenet 109(2):99–107. doi:10.1016/S0165-4608(98)00157-5
Liebisch P, Dohner H (2006) Cytogenetics and molecular cytogenetics in multiple myeloma. Eur J Cancer 42(11):1520–1529. doi:10.1016/j.ejca.2005.12.028
Palumbo A, Ambrosini MT, Benevolo G, Pregno P, Pescosta N, Callea V et al (2007) Bortezomib, melphalan, prednisone, and thalidomide for relapsed multiple myeloma. Blood 109(7):2767–2772
Sakai A, Kawano MM, Tanabe O, Kuramoto A (1993) A possible mechanism of inability of immunoglobulin heavy-chain production in Bence-Jones type myeloma cells. Int J Hematol 59(1):31–40
Szczepanski T, Van’t Veer MB, Wolvers-Tettero IL, Langerak AW, van Dongen JJ (2000) Molecular features responsible for the absence of immunoglobulin heavy chain protein synthesis in an IgH(-) subgroup of multiple myeloma. Blood 96(3):1087–1093
Zeiser R, Deschler B, Bertz H, Finke J, Engelhardt M (2004) Extramedullary vs medullary relapse after autologous or allogeneic hematopoietic stem cell transplantation (HSCT) in multiple myeloma (MM) and its correlation to clinical outcome. Bone Marrow Transplant 34(12):1057–1065. doi:10.1038/sj.bmt.1704713
Conflicts of interest statement
The authors have no potential conflicts of interest.
Author information
Authors and Affiliations
Corresponding author
Additional information
A. Kühnemund and M. Engelhardt contributed equally.
Rights and permissions
About this article
Cite this article
Kühnemund, A., Liebisch, P., Bauchmüller, K. et al. ‘Light-chain escape-multiple myeloma’—an escape phenomenon from plateau phase: report of the largest patient series using LC-monitoring. J Cancer Res Clin Oncol 135, 477–484 (2009). https://doi.org/10.1007/s00432-008-0470-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00432-008-0470-7