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    Treatment of Newly Diagnosed Myeloma (excluding t-cell redirection therapy)

    Category: Treatment of Newly Diagnosed Myeloma (excluding t-cell redirection therapy)

    Validation of a Simplified Prognostic Score for Transplant-Ineligible Multiple Myeloma Patients in a Portuguese Cohort: A Real-World Analysis Based on the Greek Myeloma Study Group Model - MEPS

    (PA-390) Validation of a Simplified Prognostic Score for Transplant-Ineligible Multiple Myeloma Patients in a Portuguese Cohort: A Real-World Analysis Based on the Greek Myeloma Study Group Model - MEPS

    Thursday, September 18, 2025

    Introduction:      The Revised International Staging System (R2-ISS) improved risk stratification in multiple myeloma (MM), but its prognostic value in transplant-ineligible (TI) patients remains uncertain. A simplified score proposed by the Greek Myeloma Study Group—based on four adverse features: age ≥75, CKD-EPI < 40 mL/min/1.73m², ECOG ≥2, and ultra-high-risk cytogenetics (UHR: ≥2 of del(17p), t(4;14), t(14;16), +1q21)—has demonstrated improved prognostic performance. We aimed to validate this Myeloma Elderly Prognostic Score (MEPS) in a real-world cohort of Portuguese TI MM patients.

    Methods:   This retrospective study included 300 newly diagnosed TI MM patients from Portuguese hospitals (2010–2024). Each MEPS variable contributed 1 point (score range 0–4). Patients were stratified by R2-ISS and MEPS. OS was estimated via Kaplan-Meier. Variables with p < 0.05 in univariable Cox regression were included in multivariable models. Bootstrapping (1000 samples) estimated 95% CIs for overall survival (OS), progression free survival (PFS), and follow-up. Discrimination was assessed with the C-index. Survival differences were evaluated by log-rank and Bonferroni-adjusted pairwise tests.

    Results:   

    Median age was 75 (49–89); 48% female. Median diagnosis year 2017. Frequencies of MEPS features: age ≥75 (53%), ECOG ≥2 (50%), CKD-EPI < 40 (35%), UHR (7%). ISS 3 and R-ISS 3 were seen in 49% and 23%. M-protein types: IgG (62%), IgA (20%), light chain (14%). R2-ISS stages: I (10%), II (29%), III (49%), IV (12%). MEPS groups: low (0 points, 23%), low-intermediate (1, 31%), intermediate-high (2, 31%), high (≥3, 15%). First-line regimens: lenalidomide-based (21%), daratumumab-based (8%), bortezomib-based or Rd (64%). Overall response rate was 83%, with 26% complete response. Second-line therapy was used in 44% and the median of post-progression OS was 22 months (n = 179, 95% CI: 17-29). At 38-month median follow-up, 52% had died. Median PFS and OS were 22 and 38 months, respectively.

    Median OS by R2-ISS: I (60), II (52), III (31), IV (25) months (p < .001); by MEPS: low (50), low-intermediate (42), intermediate-high (29), high (20) months (p < .001). Although the log-rank test did not reach conventional statistical significance (p = 0.052), the observed effect size (8 months) suggests a potentially meaningful clinical effect. In contrast, R2-ISS stages III and IV did not differ significantly (p = 0.999).
    Multivariable analysis confirmed age ≥75, CKD-EPI < 40, and ECOG ≥2 as independent predictors (p < .001); UHR trended toward significance (p = .085). MEPS showed stronger discrimination than R2-ISS for OS (C-index 0.795 vs. 0.732, p < .001) and PFS (0.762 vs. 0.676, p < .001).

    Conclusions:   MEPS effectively stratifies TI MM patients into prognostically distinct groups, outperforming R2-ISS in this cohort. Its simplicity and superior accuracy support its clinical applicability in elderly MM management. Further validation in broader cohorts is warranted.