OPTIMUM trial demonstrates value of SKY92 in detecting high-risk myeloma and improving patient outcome

On September 28, 2023 SkylineDx, an innovative diagnostics company focused on research & development of molecular diagnostics for oncology and inflammatory diseases, reported that a new peer-reviewed publication will be presented during the International Myeloma Society 20th Annual Meeting and Exposition by Dr. Martin F. Kaiser ‘Defining high risk and ultra-high risk MM (Press release, SkylineDx, SEP 28, 2023, View Source [SID1234635515]).’ The publication highlights the significant impact of SKY92 in identifying high-risk multiple myeloma patients who will benefit from an intensified treatment combination with improved survival [1].

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Identification and treatment of newly diagnosed patients with high-risk myeloma remains a global challenge. Diagnostically, there is currently an unmet need as high-risk patients could remain unidentified and experience an early relapse on standard of care treatment. Identifying aggressive disease correctly and early is therefore paramount for risk-stratified treatment approaches in myeloma.

The independent prospective multi-center UK OPTIMUM trial published in the Journal of Clinical Oncology by the UK collaborative trial group, offered patients from nearly 40 hospitals across the UK extended molecular risk screening over standard of care, by combining SKY92 with standard genetic testing for two or more high-risk markers, also termed Ultra high-risk MM (UHRMM). Patients identified as having UHRMM by either marker, or those with plasma cell leukemia (PCL), were offered intensified treatment with Dara-CVRd before and for 18 cycles after autologous stem cell transplant (ASCT). In this unique prospective molecular screening and treatment trial, SKY92 identified about 10% of NDMM patients with UHRMM who otherwise could not be identified with standard of care genetic risk markers, and vice versa, confirming prior retrospective results [2]. These patients would have effectively been missed with traditional diagnostics methods alone. In addition, the majority of PCL patients were identified by SKY92, suggesting that a wider aggressive group of disease could be diagnosed with this test in the future. Importantly, outcome of UHRMM patients treated with intensified Dara-CVRd in OPTIMUM was markedly improved over that of a digital comparator group of trial patients identified by SKY92 or standard of care genetics from the UK Myeloma XI trial: at 30 months, progression free survival (PFS) was 77% in OPTIMUM vs. 39.8% for Myeloma XI treatment. This Myeloma XI treatment is similar to standard of care. At 30 months follow up, the overall survival (OS) rate was 83.5%, vs. 73.5% using the conventional method.

"Everyone recognizes that myeloma is a highly heterogeneous disease and we now see, for the first time, markedly improved outcomes for the patients with highest unmet need, those with high-risk myeloma, with new treatment combinations. However, if we want to help and direct patients toward their best possible treatment options, we urgently need access to better molecular diagnostics as well. The sense that we are currently missing patients with aggressive disease at diagnosis is very real and confirmed by both retrospective and, with OPTIMUM, prospective evidence," said Dr. Martin F. Kaiser, Consultant Hematologist at The Institute of Cancer Research; Royal Marsden Hospital Sutton, England, United Kingdom.

"Dr. Kaiser set up a unique and innovative study design focused on a patient group in high need of new treatment strategies. The initial results, showing improved PFS and OS for the UHRMM, is an important step towards personalized treatment protocols," said Jvalini Dwarkasing, Chief Scientific Officer at SkylineDx. "We are appreciative that our SKY92 test was able to support this study by identifying UHRMM patients, indicating its utility in clinical application."

About MMprofiler with SKY92

The clinical course of MM can vary significantly between patients. This variability is related to unique characteristics of each patient’s disease. There are many treatment options available, in numerous combinations. Choosing the right treatment at the right time, while planning for future lines, is essential and can be very challenging. MMprofiler with SKY92 helps navigating these complexities. SKY92 measures the activity of 92 genes in the malignant myeloma plasma cells, and determines how aggressive the myeloma is. When myeloma is more aggressive (high-risk disease) it is less likely to respond to conventional treatments and the patient might benefit from intensification of therapy. MMprofiler with SKY92 is CE-IVD registered in Europe and available as laboratory developed test (LDT) from SkylineDx’s CAP/CLIA lab in San Diego (CA, USA).