"These results underscore the importance of bone resorption and myeloma bone disease not only for the quality of life of the patients, but also for the outcome."
Dr. Orhan Sezer
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 The Bone Resorption Marker Serum-ICTP and the Circulating Proteasome Levels Separate ISS-Stages 1-3 and Are the Most Powerful Prognostic Factors for Overall Survival in Newly Diagnosed Symptomatic Multiple Myeloma. Session Type: Poster Session, Board #629-I
Christian Jakob, Peter Liebisch, Karl Egerer, Jan Sterz, Martin Kaiser, Susanne Rötzer, Ulrike Heider, Jessica Rademacher, Claudia Fleissner, Peter M. Kloetzel, Evangelos Terpos, Orhan Sezer Department of Hematology and Oncology, Charit - Universittsmedizin Berlin; Department of Hematology and Oncology, University-Hospital Ulm; Department of Rheumatology and Clinical Immunology, Charit - Universittsmedizin Berlin; Department of Biochemistry, Charit - Universittsmedizin Berlin, Germany; Department of Medical Research, 251 General Air Force Hospital, Athens, Greece
Prognostic markers are important to identify high-risk patients in Multiple Myeloma (MM). Several prognostic models have been published, including parameters of tumor burden and cytogenetics. Recently the International Staging System (ISS) for Multiple Myeloma, which includes beta2-microglobulin (beta2-MG) and albumin, has been introduced for newly diagnosed patients with symptomatic MM. We previously reported about the prognostic significance of circulating proteasome levels (cProteasomes) in MM patients (Jakob et al., Blood 2007). In the present study we investigated the prognostic relevance of the bone resorption marker carboxy-terminal telopeptide of type-I collagen (ICTP) and cProteasome levels in comparison to the classical prognostic factors (beta2-MG), albumin, deletion 13q14 and type of chemotherapy (high-dose-therapy versus conventional dose chemotherapy) in 92 patients with newly diagnosed active MM. ICTP and cProteasome were significantly elevated parallel to ISS stages (P<0.001). ICTP (cut off: normal value), cProteasome levels (cut off: median value) and a combined ICTP-cProteasome score (1: ICTP < normal value and cProteasome < median; 2: one of both parameters elevated; 3: both parameters elevated) were significant univariate prognostic factors for overall survival in active MM (P<0.001, P=0.002 and P<0.001, respectively). Survival rates at 5-yrs were 95%, 66% and 27% in the groups of patients with ICTP-cProteasome score 1, 2 and 3, respectively. In a further analysis ICTP alone and the combined ICTP-cProteasome score significantly separated each of the three ISS stages into two distinct groups with a better versus worse prognosis. In a multivariate Cox regression analysis, including beta2-MG, albumin, deletion 13q14, type of chemotherapy, cProteasome levels and ICTP, ICTP was the parameter with the strongest prognostic power (P<0.001, hazard-ratio: 7.9) and cProteasomes (P=0.011, hazard-ratio: 3). Our study underlines that the activity of myeloma bone disease, as reflected by the collagen-I degradation product ICTP, has a major impact on the prognosis of symptomatic MM. This result is in line with published data showing a positive feedback between myeloma cells and osteoclasts, i.e. a vicious cycle. The inclusion of the bone resorption marker ICTP and cProteasome levels into multivariate models add substantial prognostic information on overall survival in newly diagnosed active MM.
Abstract #1475 appears in Blood, Volume 110, issue 11, November 16, 2007