Quantitative Integrative Survival Prediction in Multiple Myeloma Patients Treated With Bortezomib-Based Induction, High-Dose Therapy and Autologous Stem Cell Transplantation

Author:

Hummel Manuela1,Hielscher Thomas1ORCID,Emde-Rajaratnam Martina2,Salwender Hans3ORCID,Beck Susanne24ORCID,Scheid Christof5ORCID,Bertsch Uta6,Goldschmidt Hartmut67ORCID,Jauch Anna8,Moreaux Jérôme9ORCID,Seckinger Anja2,Hose Dirk2ORCID

Affiliation:

1. Deutsches Krebsforschungszentrum, Abteilung für Biostatistik, Heidelberg, Germany

2. Department of Hematology and Immunology, Myeloma Center Brussels & Labor für Myelomforschung, Vrije Universiteit Brussel (VUB), Jette, Belgium

3. Asklepios Tumorzentrum Hamburg, AK Altona and St Georg, Hamburg, Germany

4. Universitätsklinikum Heidelberg, Molekularpathologisches Zentrum, Heidelberg, Germany

5. Department I of Internal Medicine, University of Cologne, Cologne, Germany

6. Universitätsklinikum Heidelberg, Medizinische Klinik V, Heidelberg, Germany

7. Nationales Centrum für Tumorerkrankungen, Heidelberg, Germany

8. Universität Heidelberg, Institut für Humangenetik, Heidelberg, Germany

9. Institute of Human Genetics, UMR 9002 CNRS-UM, Montpellier, France

Abstract

PURPOSE Given the high heterogeneity in survival for patients with multiple myeloma, it would be clinically useful to quantitatively predict the individual survival instead of attributing patients to two to four risk groups as in current models, for example, revised International Staging System (R-ISS), R2-ISS, or Mayo-2022-score. PATIENTS AND METHODS Our aim was to develop a quantitative prediction tool for individual patient's 3-/5-year overall survival (OS) probability. We integrated established clinical and molecular risk factors into a comprehensive prognostic model and evaluated and validated its risk discrimination capabilities versus R-ISS, R2-ISS, and Mayo-2022-score. RESULTS A nomogram for estimating OS probabilities was built on the basis of a Cox regression model. It allows one to translate the individual risk profile of a patient into 3-/5-year OS probabilities by attributing points to each prognostic factor and summing up all points. The nomogram was externally validated regarding discrimination and calibration. There was no obvious bias or overfitting of the prognostic index on the validation cohort. Resampling-based and external evaluation showed good calibration. The c-index of the model was similar on the training (0.76) and validation cohort (0.75) and significantly higher than for the R-ISS ( P < .001) or R2-ISS ( P < .01). CONCLUSION In summary, we developed and validated individual quantitative nomogram-based OS prediction. Continuous risk assessment integrating molecular prognostic factors is superior to R-ISS, R2-ISS, or Mayo-2022-score alone.

Publisher

American Society of Clinical Oncology (ASCO)

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