(PA-308) Efficacy and Safety of Daratumumab-Based Schemes in Over80_Years Newly Diagnosed Multiple Myeloma(NDMM)

Multiple myeloma(MM) is the second most common hematologic malignancy.Frail patients who are ineligible for autologous hematopoietic stem cell transplantation require frontline treatment strategies that are both effective and tolerable, to delay disease progression and preserve quality of life. The incorporation of daratumumab(Dara) into standard first-line regimens VMP(bortezomib/melphalan/prednisone) and Rd (lenalidomide/dexamethasone)has demonstrated improved progression-free survival (PFS) and overall survival (OS). 

Methods:   

We conducted a retrospective,observational study including over80_NDMM patients who received Dara-based therapy between August2020 and January2025.Clinical and laboratory parameters at diagnosis included disease staging (ISS and R-ISS),cytogenetic abnormalities,renal function,serum albumin,and β2-microglobulin levels.Safety was assessed by recording adverse events(AEs) using CTCAEv5.0 and analyzing treatment modifications.Efficacy outcomes included progression rate and PFS,OS with survival Kaplan–Meier curves.


Results:   

A total of 33 patients (17 women,16 men) were included,with a mean age of 82years.Treatment regimens included Dara-BTZ–based combinations in 70% of patients (n=23;20DVMP, 3DVCP) and D-Rd in 30% (n=10). Median follow-up was 26.5 months.

Baseline values (mean):Creatinine clearance:53mL/min. Serum albumin:3.6g/d. β2-microglobulin:5.2mg/L.

Cytogenetics:High-risk:9.1%;Standard-risk:30.3%;Normal karyotype:54.5%:

Disease stage(ISS/R-ISS):Stage I:15.2%/15.1%;Stage II:39.4%/57.6%;Stage III:33.3%/9.1%

Meantreatment duration:16.8±14.4 months. Median follow-up:5.4years. Progression occurred in 7 patients (21%; 5Dara-BTZ, 2D-Rd). Seven patients (21%) died [3 due to progressive disease].
Median PFS was 40.7months [95% CI:36.8–not reached]: PFS at 1 year: 88.6%[95% CI:77.1–100]PFS at 2 years: 79%[95% CI:64–97.5]

Median OS was not reached. OS at 1year:78%[95% CI:63.8–95.4]. OS at 2 years:73.4% [95% CI:58.2–92.7]

AEs were reported in 86% of patients (n=28), mostly grade 1–2(87%).

Most common toxicities included:Hematologic (33%):anemia (20%; G1–3),neutropenia (5.5%; G1–2).Infections (29%):pneumonia (16%; G1–3).Other AEs of interest:Neurologic (18%);hepatic (n=3),gastrointestinal (n=2),vascular (n=4),dermatologic (n=1),metabolic (n=1)
Serious AEs included: one case of G4 cholestatic liver injury and one fatal septic shock (G5).
Treatment modifications occurred in 54% of patients (n=16):Temporary interruptions: 37%;Drug discontinuation:44%;Dose reductions: 19%.Specific causality was difficult to assign due to regimen complexity, except in the case of cholestatic injury, which led to daratumumab discontinuation.


Conclusions:   

Daratumumab-based regimens demonstrated a favorable safety profile in NDMM patients aged ≥80 years,with predominantly mild to moderate toxicity.The observed efficacy (PFSandOS) aligns with results from pivotal clinical trials.Maintenance with Dara-Rd or Dara-BTZ appeared both safe and effective in selected patients.