CHICAGO, IL—Single-agent daratumumab is safe and had high activity in patients with relapsed/refractory multiple myeloma, preliminary results of a dose expansion study presented at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting has found.

The preliminary overall response rate (ORR) was 35% in the 16 mg/kg cohort compared with 10% in the 8 mg/kg cohorts, reported Henk M. Lokhorst, MD, PhD, of UMC Utrecht, Utrecht, Netherlands.

Of 16 patients who had received daratumumab 16 mg/kg, two patients had a complete response, one, a very good partial response, and four, a partial response. All four patients who achieved a PR or better at the 16 mg/kg dose and who had bone marrow involvement cleared bone marrow plasma cells after treatment with daratumumab. At the 8 mg/kg dose, three of 29 patients had PRs. The current median progression-free survival (PFS) in the 16 mg/kg arm—which is immature—is 23 weeks, which is also the longest follow-up of any patient in this cohort, Dr. Lokhorst said.

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The goal of the expansion phase of the study was to evaluate safety and efficacy of two doses of daratumumab for up to 24 months using alternative dose schedules. Dr. Lokhorst presented preliminary data from the first 50 patients.

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The investigators enrolled patients who had relapsed or were refractory to at least two prior lines of therapy, including IMiDs® and proteasome inhibitors, and ineligible for autologous stem cell transplant (ASCT) at two dose levels, 8 mg/kg both with and without a 10 mg predose weekly for the first eight infusions or 16 mg/kg without predose with a 3-week washout period between the first two doses followed by seven weekly doses.

All patients were dosed every second week for 16 weeks followed by dosing every fourth week until disease progression, toxicity, or a maximum of 24 months.

In the 8 mg/kg arm, median age of the patients was 59 years (range, 38–77 years); the median number of prior treatment lines was 5 (range, 3–11 lines). In the 16 mg/kg arm, median age was 62 years (range, 51–76 years), and prior treatment lines were 4 (range, 2-12 lines).

The median number of daratumumab infusions was 10.5 (range, 1-21 infusions) in the 8 mg/kg arm versus 11.5 (range, 1-15 infusions) in the 16 mg/kg arm.

Dr. Lokhorst said that 12 patients (40%) in the 8 mg/kg dosing cohort had a serious adverse events, as did five (25%) in the 16 mg/kg cohort. No severe infusion-related reactions were seen; all were grade 1 and 2 across all four cohorts. He added that infusion times could be reduced to approximately 3.4 hours as of the third infusion.

A phase 3 trial is beginning this month of daratumumab in combination with lenalidomide and dexamethasone, with other monotherapy trials ongoing, he said.


  1. Lokhorst HM, Laubach J, Nahi H et al. Abstract 8513. Presented at: 2014 American Society of Clinical Oncology (ASCO) Annual Meeting; May 30-June 3, 2014; Chicago, IL.