Abstract
Risk stratification in multiple myeloma is important for prognostication, patient selection for clinical trials, and comparison of treatment approaches. We developed and validated a staging system that incorporates additional FISH abnormalities not included in the R-ISS and reflects the additive effects of co-occurring high-risk disease features. We first evaluated the prognostic value of predefined cytogenetic and laboratory abnormalities in 2556 Mayo Clinic patients diagnosed between February 2004 and June 2019. We then used data from 1327 patients to develop a risk stratification model and validated this in 502 patients enrolled in the MMRF CoMMpass study. On multivariate analysis, high-risk IgH translocations [risk ratio (RR): 1.7], 1q gain/amplification (RR: 1.4), chromosome17 abnormalities (RR: 1.6), ISS III (RR: 1.7), and elevated LDH (RR: 1.3) were independently associated with decreased overall survival (OS). Among 1327 evaluable patients, OS was 11.0 (95% CI: 9.2–12.6), 7.0 (95% CI: 6.3–9.2), and 4.5 (95% CI: 3.7–5.2) years in patients with 0 (stage I), 1 (stage II), and ≥2 (stage III) high-risk factors, respectively. In the MMRF cohort, median OS was 7.8 (95% CI: NR-NR), 6.0 (95% CI: 5.7-NR), and 4.3 (95% CI: 2.7-NR) years in the 3 groups, respectively (P < 0.001). This 5-factor, 3-tier system is easy to implement in practice and improves upon the current R-ISS.
Highlights
Multiple myeloma (MM) is the second most common hematologic malignancy and is responsible for approximately 2% of all cancer deaths in the United States [1]
Seq-fluorescence in-situ hybridization (FISH) probes were readily available for IGH translocations, MYC rearrangement, 1q gain (20% threshold), and chromosome 17 abnormalities
While minimal residual disease assessments are emerging as powerful predictors of survival outcomes for patients undergoing treatment, risk stratification in newly diagnosed patients has to rely on pre-treatment patient and disease characteristics [32]
Summary
Multiple myeloma (MM) is the second most common hematologic malignancy and is responsible for approximately 2% of all cancer deaths in the United States [1]. We included 1327 Mayo Clinic patients who had simultaneous data for all high-risk abnormalities found to be prognostic on multivariate analysis. ISS III and elevated LDH were both associated with increased risk of death on univariate analysis, so these were included in a final multivariate model with high-risk IgH translocations, MYC rearrangements, 1q gain/amplification, and chromosome 17 abnormalities.
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