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Development of an International Molecular Prognostic Scoring System

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YARDVILLE, NJ, June 12, 2022 (GLOBE NEWSWIRE) — Today, the MDS Foundation announced the development of a new prognostic scoring system, the IPSS-Molecular, which will significantly improve risk stratification in diagnosis to to better inform how treatment plans are constructed for patients with myelodysplastic syndromes.

“By taking into account the genetic makeup of each patient in the IPSS-M, we can now truly offer patient-tailored risk stratification,” says Dr. Elli Papaemmanuil of Memorial Sloan Kettering Cancer Center. “This will enable optimized treatment decisions tailored to those most in need of intervention, and sets a biological framework for the design of future clinical trials.”

For more than two decades, risk stratification of patients with MDS at diagnosis was based on diagnostic blood count, morphology, and cytogenetics through the International Prognostic Scoring System. In recent years, a complete catalog of mutated genes in MDS has been discovered. However, even though patients are increasingly receiving panel genetic testing at the time of diagnosis, there were no guidelines on how this information could be used clinically to guide risk stratification and treatment decisions. .

Creating an effective set of prognostic guidelines was particularly important for MDS because current clinical outcomes are very heterogeneous. In the absence of targeted therapies, risk stratification at the time of diagnosis is essential to guide treatment decisions. For example, supportive care with less toxic treatments would be considered for low-risk patients, while patients with high-risk disease require higher-intensity treatments to mitigate the risk of disease progression. leukemia and death.

International collaboration to improve risk stratification

Through the efforts of the International Working Group for the Prognosis of MDS – a consortium of expert clinicians, pathologists, computational biologists and statisticians – and under the auspices of the MDS Foundation, a total of 2,957 blood and marrow samples from patients were sampled at 24 centers in 13 countries. These samples were all uniformly sequenced by panel testing at Memorial Sloan Kettering Cancer Center and analyzed at Papaemmanuil’s lab. Each sample was profiled for mutations in 152 genes, and clinical and molecular variables were assessed for associations with leukemia-free survival, leukemic transformation, and overall survival. In order to validate the IPSS-M, the study used 754 other samples from the Japanese MDS consortium. The results of this survey, conducted by Drs Elsa Bernard, Elli Papaemmanuil and their colleagues at the IWG, ‘Molecular International Prognostic Scoring System for MDS (IPSS-M)’, have just been published in the June 12, 2022 issue. of the magazine New England Journal of Medicine Evidence.

Determination of the IPSS-M risk score and risk categories

The study found at least one driver genomic alteration in 94% of patients (41% of patients with cytogenetic alterations and 90% of patients with genetic mutations). On average, the higher the number of changes, the worse the results.

Using this data, the researchers developed the IPSS-Molecular which integrates information from 31 genetic mutations along with diagnostic and clinical parameters to provide a personalized, patient-specific risk score. The IPSS-M Risk Score indicates the continuum of prognostic risk seen in patients with MDS and produces six risk categories (very low, low, moderate low, moderate high, high, very high) that can be used to determine the eligibility criteria for clinical trials, correlative studies and therapeutic recommendations.

In addition to its effective prognostic categorization of primary MDS, the IPSS-M effectively stratifies patients with treatment-emergent MDS, a diagnostic subtype that was considered to be uniformly high risk and therefore lacked no applicable prognostic system. Compared to the previous IPSS-R, 46% (approximately 1 in 2) of patients were reassigned to a different risk category in the IPSS-M, resulting in improved prognostic discrimination. It is important to note that 7% of patients were reassigned by more than one stratum (eg, IPSS-R Low to IPSS-M High or vice versa).

The future of MDS risk stratification

The IPSS-Molecular is set to become a new international standard for risk stratification of patients with MDS at the time of diagnosis. The IPSS-M score is personalized, interpretable, reproducible and provides a flexible and transparent strategy to account for missing values. It also provides a list of 31 genes that should be considered in the design of diagnostic tests.

To support widespread adoption and use, the research team developed a web-based calculator where clinicians can enter patients’ clinical and molecular data to provide personalized prediction of risk, outcome and likelihood. transformation of leukemia to guide the cost-benefit analysis of treatment. the decisions.

“It has been a privilege to work closely with expert MDS clinicians, pathologists, biologists, statisticians and the broader IWG community to develop the IPSS-M, aiming to better guide and ultimately improve care. patients with MDS,” says Dr. Elsa Bernard of Memorial Sloan Kettering Cancer Center. “While the IPSS-M can be calculated using a relatively simple formula, we have built a web-based calculator and an R package to facilitate its application, which we hope will prove useful for the community.”

Explore the web IPSS-M Calculator.

Read it IPSS-M study.

Study investigators:

Elsa Bernard, Ph.D., Heinz Tuechler, Peter L. Greenberg, MD, Robert P. Hasserjian, MD, Juan E. Arango Ossa, MS, Yasuhito Nannya, MD, Ph.D., Sean M. Devlin, Ph. D., Maria Creignou, MD, Philippe Pinel, MS, Lily Monnier, MS, Gunes Gundem, Ph.D., Juan S. Medina-Martinez, MS, Dylan Domenico, BS, Martin Jädersten, MD, Ph.D., Ulrich Germing, MD, Guillermo Sanz, MD, Ph.D., Arjan A. van de Loosdrecht, MD, Ph.D., Olivier Kosmider, MD, Ph.D., Matilde Y. Follo, Ph.D., Felicitas Thol, MD, Lurdes Zamora, Ph.D., Ronald F. Pinheiro, Ph.D., Andrea Pellagatti, Ph.D., Harold K. Elias, MD, Detlef Haase, MD, Ph.D., Christina Ganster, Ph.D., Lionel Ades, MD, Ph.D., Magnus Tobiasson, MD, Ph.D., Laura Palomo, Ph.D., Matteo Giovanni Della Porta, MD, Akifumi Takaori-Kondo, MD, Ph.D . ., Takayuki Ishikawa, MD, Ph.D., Shigeru Chiba, MD, Ph.D., Senji Kasahara, MD, Ph.D., Yasushi Miyazaki, MD, Ph.D., Agnes Viale, Ph.D. , Kety Huberman, BS, Pierre Fenaux, MD, Ph.D., Monika Belickova, Ph.D., Michael R. Savona, MD, Virg ini a M. Klimek, MD, Fabio PS Santos, MD, Ph.D., Jacqueline Boultwood, Ph.D., Ioannis Kotsianidis, MD, Ph.D., Valeria Santini, MD, Francesc Sole, Ph.D., Uwe Platzbecker, MD, Michael Heuser, MD, Peter Valent, MD, Kazuma Ohyashiki, MD, Ph.D., Carlo Finelli, MD, Maria Teresa Voso, MD, Lee-Yung Shih, MS, Michaela Fontenay, MD, Ph. D. ., Joop H. Jansen, Ph.D., Jose Cervera, MD, Ph.D., Norbert Gattermann, MD, Benjamin L. Ebert, MD, Ph.D., Rafael Bejar, MD, Ph.D. , Luca Malcovati, MD, Mario Cazzola, MD, Seishi Ogawa, MD, Ph.D., Eva Hellstrom-Lindberg, MD, Ph.D., and Elli Papaemmanuil, Ph.D.

The MDS Foundation, Inc. is an international non-profit advocacy organization whose mission is to support and educate patients and healthcare providers through innovative research in the areas of MDS, Acute Myeloid Leukemia (AML) and associated myeloid neoplasms to accelerate progress towards the diagnosis, control and cure of these diseases.

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Media Contact:

Tracey Iraca, Executive Director, MDS Foundation, Inc.

Phone: (609) 298-1600 ext. 211

Mobile: (609) 647-2080

Email: [email protected]

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