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An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
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A simple additive staging system for newly diagnosed multiple myeloma.
Nadine H Abdallah1, Moritz Binder1, S Vincent Rajkumar1
1Division of Hematology, Mayo Clinic, Rochester, MN, USA.
Blood Cancer Journal
|February 1, 2022
Summary
A new 5-factor staging system for multiple myeloma improves risk stratification by including additional genetic abnormalities. This system enhances prognostication and patient selection for clinical trials compared to the current R-ISS.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- Accurate risk stratification is crucial for multiple myeloma (MM) management, impacting prognostication, clinical trial eligibility, and treatment comparisons.
- The current Revised International Staging System (R-ISS) has limitations in capturing the full spectrum of high-risk disease features.
- Incorporating additional genetic abnormalities beyond R-ISS criteria is needed for more precise MM risk assessment.
Purpose of the Study:
- To develop and validate a novel staging system for multiple myeloma that incorporates additional fluorescence in situ hybridization (FISH) abnormalities.
- To reflect the additive effects of co-occurring high-risk disease features in MM.
- To improve upon the existing R-ISS for better prognostication and patient stratification.
Main Methods:
- Evaluated prognostic value of cytogenetic and laboratory abnormalities in 2556 Mayo Clinic MM patients (Feb 2004 - Jun 2019).
- Developed a risk stratification model using data from 1327 patients.
- Validated the model in 502 patients from the MMRF CoMMpass study.
Main Results:
- Multivariate analysis identified high-risk IgH translocations, 1q gain/amplification, chromosome 17 abnormalities, ISS III, and elevated LDH as independent predictors of decreased overall survival (OS).
- The developed 5-factor, 3-tier system showed distinct OS outcomes: Stage I (0 factors) had 11.0 years, Stage II (1 factor) had 7.0 years, and Stage III (≥2 factors) had 4.5 years in the development cohort.
- Validation in the MMRF cohort confirmed these OS differences (7.8, 6.0, and 4.3 years, respectively), demonstrating the system's robustness (P < 0.001).
Conclusions:
- A new 5-factor, 3-tier staging system incorporating key genetic abnormalities significantly improves risk stratification in multiple myeloma.
- This system is practical for clinical implementation and offers enhanced prognostic accuracy over the current R-ISS.
- The findings support the use of this refined staging system for better patient management and clinical trial design in multiple myeloma.
