Safety of 90-minute daratumumab infusion

Daratumumab (dara) is a human IgG1κ monoclonal antibody shown to induce target-cell killing of CD38-expressing tumor cells and is approved for the treatment of relapsed and refractory multiple myeloma (RRMM) in a number of indications – click here for more information. Due to CD38 expression on airway smooth muscle cells, infusion-related reactions (IRRs) are common with the administration of dara and a number of clinical trials reported a high incidence of IRRs in MM  patients during the first infusion (95.8% from the pooled data analysis of SIRIUS and GEN501 trials). However, the incidence of IRRs decreased dramatically during second and subsequent infusions, and therefore it was hypothesized that increasing the speed of subsequent infusions would not affect the number of IRRs.

Hallie Barr, from Wexner Medical Center, Ohio State University, Columbus, USA, and colleagues, conducted a study in which they assessed the safety of an accelerated daratumumab infusion in MM patients who had previously received dara. The findings of this study were published in Leukemia in March 2018.

Study design:

• A single-center, prospective and open-label study
• Patients (pts) were enrolled between February 2017 and June 2017
• Pts eligible for the study had to have received ≥ 2 doses of daratumumab at standard infusion rates, which equated to a total volume of 550 ml daratumumab
• Protocol for the accelerated infusion:
  • 20% of the dose was given over 30 min (200 ml/hr)
  • Remaining 80% given over 60 min (450 ml/hr)
  • Total volume = 550mL; 90 minute infusion
• Monitoring of standard vital signs: prior to infusion start, every 15 min for 1 h and at the end of the infusion

Key Highlights:

• N =28 pts
• Median age (range) = 67 years (44–90)
• No of prior daratumumab doses: 2 doses = 8 pt; 3–5 doses = 7 pts; 6–9 doses = no pt; ≥10 doses = 13 pts and median (range) = 5 (2–26)
• History of daratumumab reactions: first dose = 11 pts; second dose = no pt
• An accelerated infusion was well-tolerated in all patients
• No grade 3 or above IRRs observed
• One single grade 2 hypertension event
• All pts remained on the accelerated infusion at the 4-week follow-up point

A 90-minute accelerated infusion of dara in MM patients was successful, with no serious side-effects and a reduction in IRRs. Consequently, this protocol has now been implemented as a new standard-of-care in the authors’ institutions, with the added benefit of a decrease in the use of healthcare resources.