Three-Dimensional Telomere Analysis Using Teloview® Technology Identifies Smouldering Myeloma Patients with High Risk of Progression to Full Stage Multiple Myeloma in a Proof of Concept Cohort

Multiple Myeloma (MM) remains incurable in spite of the recent development of several advanced therapeutic modalities. Similar to other incurable diseases, the early diagnosis and treatment of MM patients may lead to better prognosis and increased survival rates. Multiple myeloma follows two asymptomatic precursor lesions, monoclonal gammopathy of undetermined significance (MGUS) and smouldering myeloma (SMM) [1]. In current clinical practice patients diagnosed with MGUS or SMM are monitored but not treated. MGUS and SMM may progress to the full stage of multiple myeloma at any time without clinically detectable signals. While 1% of MGUS patients progress to full stage MM every year, 10% of SMM patients progress to full stage MM every year [1]. In this study, we report for the first time that the 3-dimensional telomeres analysis using the TeloView® software platform is able to identify SMM patients with high risk of progression to full stage MM. The prospective study we conducted included a proof of concept cohort of total 21 SMM patients, 16 patients that remained stable for over 5 years, and 5 patients progressed to full stage multiple myeloma within 1 to 3 years from point of diagnosis. The disease progression of high risk SMM patients was confirmed clinically by MM caused morbidity. TeloView® analysis of the 2 SMM patient-groups revealed with high significance (p <0.001) distinct telomeres profiles of the stable patients versus the patients who progressed to full stage MM across 5 independent telomeric parameters measured by TeloView®. The study was conducted blindly on the diagnostic specimens suggesting the ability of TeloView® analysis to stratify SMM patients at point of diagnosis. The results we report have the potential, for the first time, to guide evidence-based decisions to treat SMM patients with high risk of progression, addressing a critical unmet clinical need in the management of MM. Follow up studies including expanded cohorts are needed to validate the results of this study, and to confirm the utility of TeloView® technology to predict the progression of SMM patients on the level of the individual patient.

References:

1. Boutros M. et al Genomic Profiling of Smouldering Multiple Myeloma Identifies Patients at a High Risk of Disease Progression. J Clin Oncol. 2020 Jul 20;38(21):2380-2389