Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma

Saad Z. Usmani, Brendan M. Weiss, Torben Plesner, Nizar J. Bahlis, Andrew Belch, Sagar Lonial, Henk M. Lokhorst, Peter M. Voorhees, Paul G. Richardson, Ajai Chari, A. Kate Sasser, Amy Axel, Huaibao Feng, Clarissa M. Uhlar, Jianping Wang, Imran Khan, Tahamtan Ahmadi and Hareth Nahi

Key points

  • A pooled analysis of 2 daratumumab monotherapy trials showed no new safety signals, an ORR of 31%, and rapid, durable, and deep responses.

  • Median overall survival was 20.1 months (95% CI, 16.6-NE); benefit was also shown in patients who achieved minimal response/stable disease.


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.

  • Submitted March 14, 2016.
  • Accepted May 6, 2016.