DP116 | FRAILTY SCORE, SARCOPENIA AND MYOSTEATOSIS: STRATIFYING RISK AND OUTCOMES IN NON-TRANSPLANT ELIGIBLE MULTIPLE MYELOMA PATIENTS TREATED WITH DARATUMUMAB-BASED DOSE-ADJUSTED COMBINATION THERAPIES

Background: Daratumumab-based regimens are standard in non-transplant eligible (NTE) newly diagnosed multiple myeloma (NDMM), but frail patients show poorer outcomes due to reduced treatment tolerance. Dose reductions are recommended to balance efficacy and safety. Sarcopenia and myosteatosis—loss of skeletal muscle mass and quality—are emerging prognostic markers, assessable via CT at L3 and complementing geriatric scores. Aims and Methods: We retrospectively analyzed 94 NTE NDMM patients diagnosed between April 2021 and January 2024, treated with DRD or DVMP. To enhance tolerability, DRD included reduced dexamethasone (20 mg weekly in cycles 1–2, then 10 mg as premedication in responsive patients); other agents were adjusted per EHA-ESMO guidelines. Frailty was assessed by IMWG score, grouping fit and intermediate-fit as non-frail. Sarcopenia was defined by low skeletal muscle index (SMI) using gender-specific cut-offs. Myosteatosis was assessed via intermuscular adipose tissue (IMAT) and myosteatosis index (MS), calculated as the ratio of skeletal muscle density (SMD) to subcutaneous adipose tissue density (SATD). ORR, PFS, OS, and safety were evaluated by by using frailty, sarcopenia, and myosteatosis. Results: Patients’ characteristics are listed in table 1. Sarcopenia was present in 73% (63% frail vs 36% non-frail, p=0.05). Dose reduction was applied in 79% overall and 100% of frail patients. ORR was 83% (≥VGPR 65%, CR 17%, sCR 1%). After a median follow-up of 25 months, two-years PFS was 78% and two-years OS was 89%. No significant differences were observed by regimen (PFS 80% vs 70%, p=0.67; OS 90% vs 84%, p=0.79), frailty (PFS 84% vs 73%, p=0.26; OS 94% vs 85%, p=0.16), or sarcopenia (PFS 80% vs 72%, p=0.86; OS 90% vs 86%, p=0.83). When stratifying by myosteatosis parameters, patients in the highest quartile for IMAT had significantly inferior 2-year PFS (65% vs 84%, p=0.04) and OS (78% vs 92%, p=0.03). Similarly, patients in the highest quartile for MS showed inferior 2-year PFS (68% vs 85%, p=0.03) and OS (80% vs 93%, p=0.04). No significant differences in adverse events were observed among subgroups, with no relevant safety concerns. Conclusion: DRD and DVMP are effective and safe in real-life NTE NDMM. Upfront dose-reduction, including dexamethasone sparing, improves tolerability, even in frail patients. While sarcopenia shows limited prognostic value, myosteatosis (IMAT, MS) appears more sensitive and may support tailored treatment strategies.