P-117: A prognostic score based on age, eGFR (CKD-EPI), performance status and ultra-high-risk disease outperforms R2-ISS for elderly myeloma patients: An analysis of the Greek Myeloma Study Group Registry

Introduction: Second revision of ISS (R2-ISS) enhanced the prognostic value of R-ISS; however, its impact on transplant ineligible (TI) Multiple Myeloma (MM) patients was not clearly defined. We aimed to evaluate prognostication of R2-ISS in TI population in the real-world in comparison with other well-known prognostic factors for OS i.e., age, performance status, renal function, and ultra-high-risk MM (UHR).

Methods: We analyzed 780 newly diagnosed TI MM patients with complete data for R2-ISS diagnosed between 2003-2022 (median age 74 years, range 65-91; M/F: 384/396; IgG: 475, IgA: 209, light chain: 75, IgD: 7, non-secretory: 11, IgM: 3).

Results: Forty-seven percent were ≥75 years, 52% had ECOG ≥2, 27% had CKD-EPI eGFR < 40mL/min/1.73m2, 46% had anemia (Hb < 10g/dL), and 29%/12% had ISS-3/R-ISS-3, respectively. Per R2-ISS, 128 patients were classified in low (I), 254 in low-intermediate (II), 355 in intermediate-high (III) and 43 in high risk (IV) group; UHR MM [including two of the following: del17p, t(4;14), t(14;16) and +1q21] was found in 68/780 (8.7%) patients. Regarding therapy, 215 patients received upfront either lenalidomide-based triplets (LBT; n=135) or daratumumab-based regimens (DBR; n=80) (28%) . The rest received mostly bortezomib combinations or Rd (389; 50%); ORR was 83% (CR: 18%). After a median follow up of 72 months (mo) (95% CI: 65-79), 478 patients died (61%); median PFS and OS was 24 mo (95% CI: 22-26) and 50 mo (95% CI: 44-56), respectively; 2nd line therapy was given in 369/780 patients; median post-progression OS was 17 mo (95% CI: 13-20). In the univariate cox regression analysis age ≥75 vs. 65-74, R-ISS, R2-ISS, UHR MM, ECOG ≥2, CKD-EPI < 40 vs. ≥40 mL/min/1.73m, anemia and treatment with LBT/DBR were significant predictors for OS. Age ≥75, CKD-EPI < 40 mL/min/1.73m2, ECOG ≥2 and UHR MM maintained their negative prognostication in the multivariate analysis [HzRs: age ≥75: 1.4, CKD-EPI < 40 mL/min/1.73m2: 1.57, ECOG ≥2: 1.76 and UHR MM: 1.6; p< 0.05); prognostic significance of R2-ISS was marginal (p=0.05). Median OS for R2-ISS I-IV was, 72.6 mo (95% CI: 59-86), 66 mo (95%CI: 53-82), 43 mo (95% CI: 37-49) and 15 mo, respectively (p < 0.001). Age ≥75, CKD-EPI < 40, mL/min/1.73m2, ECOG ≥2 and UHR MM, scoring 1 point each, composed a model that recognized 4 prognostic risk groups: low: 0 points, low-intermediate: 1 point, intermediate-high 2 points and high ≥3 points. Median OS for patients classified as low risk (n=185), low-intermediate (n=298), intermediate-high (n=203) and high (n=94) was 79 mo (95% CI: 65-92), 60 mo (95% CI: 52-68), 42 mo (95% CI: 36-48) and 15 mo (95% CI:9-20), respectively (HzR: low vs. high: 0.21, low-intermediate vs. high: 0.32 and intermediate-high vs. high: 0.46; p< 0.001).

Conclusions: In conclusion, age ≥75 years, CKD-EPI < 40mL/min/1.73m2, ECOG≥2 and UHR MM were the strongest negative predictors for OS, building up a 4-group prognostic score for TI MM patients. Prognostic impact of R2-ISS was marginal. Further validation is warranted.