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

Manuela Hummel, Thomas Hielscher, Martina Emde-Rajaratnam, Hans Salwender, Susanne Beck, Christof Scheid, Uta Bertsch, Hartmut Goldschmidt, Anna Jauch, Jérôme Moreaux, Anja Seckinger, Dirk Hose

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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.

Original languageEnglish
Article numbere2300613
Number of pages12
JournalJCO precision oncology
Volume8
DOIs
Publication statusPublished - Jul 2024

Bibliographical note

Funding Information:
Supported by the German Federal Ministry of Education (BMBF) CLIOMMICS (FKZ 01ZX1309 and FKZ 01ZX1609) and CAMPSIMM (FKZ 01ES1103). The HOVON65/GMMG-HD4 (EudraCT no. 2004-000944-26) and GMMG-MM5 trial (EudraCT No. 2010-019173-16) were funded as previously reported.

Funding Information:
The authors thank Maria D\u00F6rner, Ewelina Nickel, and Birgit Schneiders for technical assistance in the enrichment of CD138-positive plasma cells; Tine Borowski, Michaela Brough, Michelle Ebentheuer, Marie-Christine Meffert, and Stephanie Pschowski-Zuck for technical assistance in iFISH; and V\u00E9ronique Pantesco for performing DNAmicroarrays, as well as the Transcriptomics Platform at CHU Montpellier.

Publisher Copyright:
© 2024 American Society of Clinical Oncology.

Keywords

  • Multiple Myeloma/mortality
  • Humans
  • Bortezomib/therapeutic use
  • Male
  • Female
  • Middle Aged
  • Transplantation, Autologous
  • Nomograms
  • Aged
  • Prognosis
  • Hematopoietic Stem Cell Transplantation
  • Antineoplastic Agents/therapeutic use
  • Induction Chemotherapy
  • Adult
  • Survival Rate

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