Real-World Evidence Supports Split Daratumumab Dosing in Myeloma

Robert M. Rifkin, MD

Split dosing with daratumumab (Darzalex) was found to be comparable with a standard dosing schedule in terms of safety and efficacy in patients with multiple myeloma in first infusion, suggesting greater convenience for patients and providers alike.

In a retrospective, observational analysis that was presented at the 2018 ASH Annual Meeting, patients who had started on daratumumab therapy within any US Oncology Network practice between November 2015 and June 2017 were eligible for evaluation. Descriptive analyses revealed that the majority of patients were male (54.2%) and Caucasian (78.3%), with a median age of 63.6 years. Aside from Karnofsky performance status, which was higher in patients who received split dosing than in those who received standard dosing (P = .02), no other differences in baseline characteristics were observed.

Of the 622 patients included in the analysis, 58.5% (n = 364) received split dosing and 41.5% (n = 258) received a standard first dose of 1 infusion at 16 mg/kg. Split dosing, as outlined in the US Oncology Network protocol, was given at 50 mL/hour. If no infusion events occurred within the first hour, the infusion rate was increased in 50-mL/hour increments every hour, not exceeding 200 mL/hour.

A shorter infusion duration was noted on day 1 in the split dosing cohort than in the standard dosing cohort, with respective median infusion lengths of 4.5 hours (range, 0.1-8.1) and 6.5 hours (range, 0.7-9.9; P <.0001). However, the median total infusion time with split dosing (8.7 hours) exceeded that of standard dosing (6.5 hours).

Though not statistically significant, split dosing resulted in a lower rate of infusion reactions than with standard dosing. In a random sample of infusion reactions taken from both cohorts (n = 302), 47.8% of patients (n = 88) who received split dosing and 48.3% of patients (n = 57) who received standard dosing experienced ≥1 infusion reaction. The most common infusion reactions were lower-respiratory (26.1%), upper-respiratory (17.2%), gastrointestinal in nature (12.5%), chills (8.9%), and flushing (6.6%).

Notably, more patients received split dosing as opposed to standard dosing over the course of the study (P <.0001). Though standard dosing was more common among patients between the first two quarters of daratumumab administration (2015/Q4: 6/22; 2016/Q1: 33/48), split dosing superseded its use in the latter portion of the study (2016/Q2: 34/31; 2016/Q3: 48/35; 2016/Q4: 44/37; 2017/Q1: 101/55; 2017/Q2: 98/30).

“We hope going forward, this will be a direction we move toward in multiple myeloma, so that we are not just looking at all the hard, clinical data, but the convenience of infusion and its impact on patients and their caregivers,” said lead study author Robert M. Rifkin, MD.

OncLive: How did split dosing with daratumumab compare with its traditional infusion?

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In an interview with OncLive, Rifkin, attending physician, Rocky Mountain Cancer Centers, research lead, Multiple Myeloma, The US Oncology Network, highlighted the results of this trial evaluating the safety of split-dosing administration of daratumumab in patients with multiple myeloma.Rifkin: This is a very important time in multiple myeloma with the advent of many new agents. In the presentation [at the 2018 ASH Annual Meeting], we discussed making the administration of daratumumab easier in the clinic and in the community. In the initial studies that were done with daratumumab, the first infusion took around 10 hours or so. In our poster, we studied patients who received this single infusion versus splitting the dose over the course of 2 days. We showed that there's a decrease in infusion reactions with split dosing. It was also much more convenient for patients and their caregivers.We went back and looked at [the data] from a health economics and outcomes research standpoint using our electronic medical records, as well as some other tools. In this case, we were able to present very nice, real-world evidence on splitting the dose of daratumumab.The next steps will be to let the data mature. Then, we'll start to look at integrating this approach with daratumumab split-dose infusions into other research and open studies.

Rifkin R, Singer D, Aguilar K, et al. Safety of split first dosing vs standard dosing administration of daratumumab among multiple myeloma patients treated in a US community oncology setting: a real-world observational study. In: Proceedings from the 2018 ASH Annual Meeting; December 4-8, 2018; San Diego, CA. Abstract 4846.