Study Design

  • Phase 2, open-label, multicentre study
  • Patients randomized 1:1 to receive daratumumab
    • 8 mg/kg every 4 weeks, or
    • 16 mg/kg every week for 8 weeks, every 2 weeks for 16 weeks, then every 4 weeks thereafter
  • Response was evaluated at first interim
    analysis and 16 mg/kg daratumumab was
    established as the recommended dose for
    further study
  • Results are reported for all patients who
    were treated with 16 mg/kg
    daratumumab (n = 106)

Inclusion Criteria

  • 18 years of age
  • Documented secretory multiple myeloma and evidence of disease progression
  • Responded to at least one previous treatment regiment
  • Received ≥ 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or have disease refractory to both a PI and IMiD
  • Received an alkylating agent alone or in combination with other myeloma treatments
  • Absolute neutrophil count >1 x 109/L
  • Hemoglobin > 7.5 g/dL
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  • Platelet count ≥ 50 x 109/L
  • Creatinine clearance > 20 ml/min/1.73 mm2

Exclusion Criteria

  • Any anti-myeloma treatment within 2 weeks
  • Autologous stem cell transplantation within 12 weeks
  • Meningeal involvement of multiple myeloma and other malignancies within 5 years
  • Myocardial infarction within 1 year
  • Uncontrolled or unstable angina
  • Congestive heart failure
    (NYHA Class III or IV)
  • Arrhythmia (≥ grade 2)
  • QTcF interval > 470 ms
  • Chronic obstructive pulmonary disease
  • Persistent or a history of asthma within 5 years

Efficacy Endpoints

  • Primary Endpoint
    • Overall response rate (ORR)
      • ORR = Stringent complete response (sCR) + complete
        response (CR) + very good partial response (VGPR) + partial
        response (PR)
  • Secondary Endpoint
    • Duration of response
    • Progression-free survival (PFS)
    • Overall survival (OS)
    • Clinical benefit rate (minimal response [MR] + ORR)

Safety

  • Safety assessments included:
    • Monitoring of adverse events (AEs)
    • Physical examinations
    • Electrocardiogram monitoring
    • Clinical laboratory measurements
    • Vital sign measurements
    • ECOG performance status