Real-world prospective data confirms improved risk stratification in multiple myeloma using SKY92 gene expression profiling

• According to clinical guidelines, high-risk myeloma patients should receive intensified treatment regimens. However, heterogeneity in clinical markers and staging systems lead to various interpretations of the high-risk multiple myeloma patient.
• The gene expression-based signature SKY92 is a standardized and precise tool to identify high-risk myeloma patients with significantly shorter progression-free (PFS) and overall survival (OS).

ROTTERDAM, Netherlands and SAN DIEGO, June 12, 2025 /PRNewswire/ -- SkylineDx, an innovative diagnostics company specializing in molecular diagnostics for oncology, inflammatory, and infectious diseases, proudly announces the publication of new results from the PRospective Observational Multiple Myeloma Impact Study (PROMMIS) in the British Journal of Haematology^[1]. The paper prospectively validates SKY92's prognostic performance using real-world data and assesses its impact on risk classification and (hypothetical) treatment decisions compared to conventional markers. This prospective, real-world study reinforces the clinical utility of the SKY92 gene expression profiling (GEP) classifier in improving risk stratification and guiding treatment decisions in multiple myeloma (MM) patient care.

Key findings:

• A total of 251 newly diagnosed multiple myeloma patients were enrolled in 9 top-tier US cancer centers; this all-comers study allows for a broad and diverse patient population, mimicking the real-world setting.
• Progression-Free Survival (PFS) showed a significant difference between the standard- and high-risk groups, while Overall Survival (OS) did not differ significantly based on conventional clinical risk markers.
• Risk stratification by SKY92 showed significant differences in both survival PFS and OS endpoints:
  - SKY92 standard-risk patients have a 3-year PFS and OS of 66% and 92% respectively
  - SKY92 high-risk patients have a 3-year PFS and OS of 39% and 76% respectively

The study demonstrates that integrating SKY92 into routine practice can enhance prognostic accuracy and support personalized treatment planning, marking an important milestone toward the widespread clinical implementation of the SKY92 classifier in MM management. The PROMMIS study was made possible through the close collaboration of nine renowned U.S. hospitals and research centers. Together, these institutions enrolled 251 newly diagnosed multiple myeloma (NDMM) patients between 2018 and 2021. This broad representation underscores the generalizability of the study's findings to clinical practice. The study prospectively confirmed that SKY92 significantly improves risk stratification over conventional clinical and genetic markers. Patients classified as high risk by SKY92 exhibited significantly shorter PFS and OS, validating the signature's prognostic strength in real-world data.

After receiving SKY92 results, clinicians revised their initial hypothetical treatment plans in 50% of the cases. By accurately identifying high-risk patients, SKY92 supports more intensive or trial-based treatment approaches for those who need them. At the same time, by accurately identifying standard-risk patients, SKY92 can reduce the overestimation of risk in patients who may not require aggressive treatment, minimizing unnecessary toxicity associated with intensive therapy. The integration of SKY92 into clinical decision-making increased physician confidence in 40% of cases. Clinicians reported greater certainty and objectivity when interpreting complex risk profiles, leading to improved alignment of treatment with patient prognosis.

"These findings offer strong evidence that SKY92 can help clinicians better define high-risk multiple myeloma patients, enabling more targeted and appropriate therapeutic strategies," said Dr. Noa Biran, M.D., study investigator and Associate Professor at Hackensack Meridian School of Medicine.

"This publication confirms years of scientific work and collaboration," said Jvalini Dwarkasing, PhD, Chief Scientific Officer at SkylineDx. "The SKY92 signature brings molecular precision to the clinic, giving physicians a powerful tool to reduce uncertainty in a highly complex disease. It's incredibly rewarding to see its positive impact on real-world patient care".

The results from the PROMMIS study underscore the powerful role SKY92 can play in modernizing risk stratification and guiding personalized treatment decisions for multiple myeloma patients. By providing molecular-level insights that outperform traditional risk assessment tools, SKY92 supports clinicians in delivering more precise, confident, and effective care. This study brings us one step closer to making precision medicine a standard in hematology and reaffirms SkylineDx's commitment to improving patient outcomes through innovation in diagnostics.

About SKY92

Multiple Myeloma is a heterogeneous disease, and its course can vary significantly between patients. The SKY92 biomarker enhances biological insights into the disease. This molecular diagnostic test 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. The test is CE-IVD registered in Europe and available as laboratory developed test (LDT) from SkylineDx's CAP/CLIA lab in San Diego (CA, USA).

About SkylineDx

SkylineDx is a biotechnology company focused on research and development of molecular diagnostics in oncology, inflammatory, and infectious diseases. SkylineDx uses its expertise to bridge the gap between academically discovered gene expression signatures and commercially available diagnostic products with high clinical utility, assisting healthcare professionals in accurately determining the type or status of disease or predicting a patient's response to treatment. Based on test results, healthcare professionals can tailor the treatment approach to the individual patient. SkylineDx is headquartered in Rotterdam, the Netherlands, complemented by a US base of operations and a CAP/CLIA certified laboratory in San Diego California, USA. To learn more about SkylineDx, please visit www.skylinedx.com.

Footnotes:

^1. N. Biran et. al., Enhancing risk stratification and treatment decision in Multiple Myeloma with SKY92 GEP in real-world data. Link to original article.

Media Contact:
Alexis Feinberg
ICR Healthcare
+1-203-939-2225
alexis.feinberg@icrhealthcare.com