The efficacy and favorable safety profile of daratumumab monotherapy in multiple myeloma (MM) was previously reported. An updated pooled analysis of 148 patients treated with daratumumab 16 mg/kg is presented. Data were combined from part 2 of a "first-in-human," phase 1/2 study of patients who relapsed after or were refractory to ≥2 prior therapies and a phase 2 study of patients previously treated with ≥3 prior lines of therapy (including a proteasome inhibitor [PI] and immunomodulatory drug [IMiD]) or were double refractory. Among the pooled population, patients received a median (range) of 5 (2-14) prior lines of therapy, and 86.5% were double refractory to a PI and IMID. Overall response rate was 31.1%, including 13 very good partial responses, 4 complete responses, and 3 stringent complete responses. The median duration of response was 7.6 months (95% confidence interval [CI], 5.6-not evaluable [NE]). The median progression-free survival (PFS) and overall survival (OS) was 4.0 months (95% CI, 2.8-5.6) and 20.1 months (95% CI, 16.6-NE), respectively. When stratified by responders versus stable disease/minimal response versus progressive disease/NE, median PFS was 15.0 months (95% CI, 7.4-NE) versus 3.0 months (95% CI, 2.8-3.7) versus 0.9 months (95% CI, 0.9-1.0), respectively, and median OS was NE (95% CI, NE-NE) versus 18.5 months (95% CI, 15.1-22.4) versus 3.7 months (95% CI, 1.7-7.6), respectively. No new safety signals were identified. In this pooled dataset, daratumumab 16 mg/kg monotherapy demonstrated rapid, deep, and durable responses, with a clinical benefit that extended to patients with stable disease or better.