P183 | DELAYED DARATUMUMAB ADDITION TO LENALIDOMIDE-DEXAMETHASONE IN OLDER MULTIPLE MYELOMA PATIENTS: INSIGHTS FROM REAL-WORLD DATA

Introduction In patients (pts) with multiple myeloma (MM), the combination of daratumumab, lenalidomide, and dexamethasone (Dara-Rd) is a standard of care, approved both for frontline treatment of non-transplant eligible (NTE) pts and in the relapsed/refractory (RR) setting. In real-life practice, however, it happens that clinicians prefer to start therapy with Rd and add daratumumab later, often due to advanced age or frailty. Limited evidence exists on the effectiveness of this stepwise approach. Methods We retrospectively analyzed a cohort of NTE newly diagnosed and RR MM pts treated at our institution with Rd with the intention to reassess daratumumab eligibility during therapy. Pts characteristics, timing of daratumumab initiation, and clinical factors influencing its addition or omission were collected. Frailty was assessed using the IMWG frailty score. The aim was to provide insights into delayed daratumumab addition to guide clinical decision-making. Results A total of 38 pts was included. Median age was 78 years (IQR 73-81). Based on frailty assessment, 18% were fit, 47% intermediate-fit, and 34% frail. Eleven percent had prior autologous stem cell transplantation (ASCT), and 47% were newly diagnosed. The median number of prior lines of therapy was 1. The mean starting doses were 17.4 mg for lenalidomide and 16.8 mg for dexamethasone. The cumulative incidence of daratumumab initiation was 41.1% at 3 months and 58.8% at 6 months. Factors associated with lower likelihood of daratumumab initiation included age >78 years (HR 0.83, p=0.020), frailty score 2 (HR 0.10, p=0.025), and higher starting lenalidomide dose (>15 mg/d) (HR 0.95, p=0.023). Prior ASCT (HR 4.02, p=0.053) and higher starting dose of dexamethasone (20mg/d) (HR 1.17, p<0.001) were associated with an increased likelihood of adding daratumumab. Conclusion This real-world analysis suggests that stepwise addition of daratumumab to Rd in older or frail pts with MM is feasible in clinical practice. Daratumumab initiation was less likely in older, frailer pts or those starting on higher lenalidomide doses, possibly reflecting clinical caution in pts with early favorable response or limited tolerance. Conversely, prior ASCT and higher dexamethasone dose were associated with increased daratumumab initiation, possibly identifying fitter pts suitable for treatment intensification. Detailed outcome data stratified by daratumumab initiation status will be presented at the conference.