Oral Presentation 29th Australian and New Zealand Bone and Mineral Society Annual Scientific Meeting 2019

Serum CTX-1 levels to predict smouldering myeloma patients at high risk of progression to multiple myeloma (#29)

Melissa D Cantley 1 2 , Kate Vandyke 1 2 , Cindy Lee 3 , Oi-Lin Lee 3 , Noemi Horvath 3 , Bik To 3 4 5 , Andrew CW Zannettino 1 2
  1. Myeloma Research Laboratory, School of Biomedicine, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, South Australia, Australia
  2. Cancer Program, Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
  3. Department of Haematology, Royal Adelaide Hospital, Adelaide, South Australia, Australia
  4. Department of Haematology, SA Pathology, Adelaide, South Australia, Australia
  5. Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, South Australia, Australia

Osteolytic bone disease affects up to 90% of patients with the hematological malignancy multiple myeloma (MM). Patients with asymptomatic pre-malignant stages known as monoclonal gammopathy of undermined significance (MGUS) and smouldering myeloma (SMM) do not have detectable osteolytic lesions but do show evidence of abnormal bone remodelling. Histomorphometric studies suggest increased bone resorption may be characteristic of SMM and MGUS patients at high-risk of progression to MM. We therefore aimed to investigate whether serum levels of the bone resorption marker C-terminal telopeptide 1 (CTX-1) may identify patients at high-risk of progression to active MM.

Serum CTX-1 levels were assessed in previously untreated patients with MGUS (n=67) or SMM (n=29). CTX-1 measurements were performed using a Roche E170 automated immunoassay analyser. Disease progression was defined by development of active MM following the International Myeloma Working Group (IMWG) diagnostic criteria. Patients with newly diagnosed active MM (n=304) were included as controls.

In the MGUS cohort, 14.9% of patients progressed during follow-up (median follow up: 141.7 weeks; range: 2-797 weeks); there was no significant difference in time-to-progression in patients with high or low CTX-1 levels (stratified at median=349 ng/L, p=0.4, log-rank test). In the SMM cohort, 40% of patients progressed within 47.4 weeks (range: 2-234 weeks) of follow-up. Notably, time to progression was significantly shorter in patients with high CTX-1 levels (above cohort median:315 ng/L) with a median time to progression of less than one year (median: 45.6 weeks), compared with 106.1 weeks in the CTX-1 low cohort (p=0.02, log-rank test).

Results suggest that elevated CTX-1 levels may predict patients at high-risk of rapid progression to active MM. These data provide proof-of-concept for future prospective studies to assess whether identification of high-risk SMM patients on the basis of CTX-1 levels may identify those who would benefit from increased monitoring or early therapeutic intervention.