Objectives: The CANDOR trial showed that KdD (carfilzomib, dexamethasone, and daratumumab) improved progression-free survival (PFS) vs Kd (carfilzomib and dexamethasone; hazard ratio, 0.63; 95% confidence interval, 0.46–0.85) in patients with relapsed or refractory multiple myeloma (RRMM). We present the results of subgroup analyses in CANDOR by number of prior lines of therapy (pLOTs) and prior therapies (Tx). Material and methods: Patients with RRMM (1–3 pLOTs) were randomized 2:1 to receive KdD or Kd. The primary endpoint was PFS; secondary endpoints included overall response rate (ORR), minimal residual disease (MRD)–negative complete response (CR) at 12 months (threshold, 10−5), and safety. Patients were evaluated by number of pLOTs and prior lenalidomide (LEN) or bortezomib (BOR) Tx. Results: Of the 466 patients randomized, 43% had one pLOT; 57% had ≥ 2 pLOTs; 42% were LEN exposed; 33% were LEN refractory; 91% were BOR exposed; and 33% were BOR refractory. Treatment effects were generally consistent and improved with KdD vs Kd treatment across subgroups for PFS, ORR, and MRD-negative CR rates. Median PFS could not be estimated in most subgroups, especially in the KdD treatment arm, except for BOR refractory (14.2 months for KdD vs 14.9 months for Kd). The ORR for the one-pLOT subgroup was 90% for KdD vs 76% for Kd; these rates were 80% vs 74% for ≥ 2 pLOTs, 79% vs 74% for LEN exposed, 88% vs 75% for LEN naïve, 80% vs 73% for LEN refractory, 86% vs 76% for LEN nonrefractory, 79% vs 69% for BOR refractory, and 87% vs 78% for BOR nonrefractory. The interaction test for all presented subgroups (treatment by subgroup) was not statistically significant (with multivariate model adjusting for other baseline factors as appropriate). MRD-negative CR rates were consistently higher in KdD-treated patients vs Kd-treated patients across all subgroups (eg, 17% vs 2% for one pLOT, 10% vs 1% for ≥ 2 pLOTs, 11% vs 0% for LEN exposed, 13% vs 3% for LEN naïve, 13% vs 0% for LEN refractory, 12% vs 2% for LEN nonrefractory, 7% vs 2% for BOR refractory, and 15% vs 1% for BOR nonrefractory). The rate of grade ≥ 3 treatment-emergent adverse events in the pLOT subgroups (83% KdD vs 74% Kd for one pLOT and 82% KdD vs 74% Kd for ≥ 2 pLOTs) was similar to that in the broader CANDOR population. A comprehensive analysis of these subgroups, including patient characteristics and safety profiles, will be presented at the meeting. Discussion: Median PFS was not reached in the KdD treatment arm in most subgroups. While there were no differences in overall survival, KdD-treated patients across multiple subgroups had better ORR and MRD-negative CR rates compared with Kd-treated patients. Conclusion: Safety and efficacy results were generally consistent across subgroups, irrespective of LEN- or BOR-refractory status or number of pLOTs. ClinicalTrials.gov: NCT03158688. This encore abstract was accepted and originally published at EHA 25 Virtual (European Hematology Association) in June 2020.