Results of a Time and Motion Survey Regarding Subcutaneous versus Intravenous Administration of Daratumumab in Patients with Relapsed or Refractory Multiple Myeloma

Abstract

Purpose Daratumumab (DARA) is a humanized anti-CD38 monoclonal antibody and approved as monotherapy or in combination with standard of care regimens for the treatment of multiple myeloma (MM). DARA intravenous (IV) administration is time-consuming; availability of DARA subcutaneous (SC) is expected to reduce this burden. A time and motion survey was undertaken to elicit healthcare providers’ (HCPs’) understanding of the workflow and time estimates for administration of DARA IV and SC (beyond treatment time) in patients with relapsed/refractory MM. Patients and Methods This web-based, prospective survey collected data from HCPs at sites that actively enrolled patients in the phase 3 COLUMBA trial, a multicenter, noninferiority study of DARA IV versus DARA SC. Data collection included time actively spent on pre-specified drug preparation and drug administration/patient care activities; active HCP and chair time were extrapolated for first and subsequent treatments. Results Compared with DARA IV, DARA SC reduced median total active HCP time by 63.8% (from 265.9 to 96.3 minutes) and 49.5% (from 179.2 to 90.4 minutes) for first and subsequent treatments, respectively. When extrapolated to the anticipated number of treatments per year (23 in Year 1 and 13 in Year 2, per label), estimated active HCP time per patient was reduced by 50% in Years 1 (from 70.1 to 34.8 hours) and 2 (from 38.8 to 19.6 hours) for DARA SC versus DARA IV. Estimated chair time for DARA SC was decreased by 97% versus DARA IV for first (from 456.9 to 13.3 minutes) and subsequent treatments (from 238.0 to 8.1 minutes). Conclusion These results suggest that DARA SC is associated with less active HCP involvement during drug preparation and drug administration/patient care compared with DARA IV, potentially reducing burdens on patients and caregivers and creating efficiencies for HCPs and healthcare facilities, allowing more patients access to care.

Clinical Administration Characteristics of Subcutaneous and Intravenous Administration of Daratumumab in Patients With Multiple Myeloma at Mayo Clinic Infusion Centers

“…Other analyses have offered web-based prospective survey data on clinic time parameters and general observations on time in clinic on the basis of treatment protocols. [15][16][17] However, an empirical method for uniformly assessing individual patient time in clinic has not been described. In this study, a novel empirical data extraction approach was applied to the electronic health records (EHRs) system at the Mayo Clinic to describe DARA administration characteristics, including time parameters of interest related to in-clinic patient management.…”

Drug resistance in multiple myeloma: Soldiers and weapons in the bone marrow niche

“…In 2014, Lohr et al. showed that genes encoding RAS family members are the most frequently mutated genes in MM ( 100 ), which raised interest in BRAF/MEK targeting ( 101 – 104 ).…”

“…Mitsiates et al., demonstrated that TNF–related apoptosis-inducing ligand/Apo2 ligand (TRAIL/Apo2L) causes apoptosis in human MM cells, MM cell lines, and the MM cells of patients with disease either sensitive or resistant to dexamethasone (Dex) and chemotherapy. Doxorubicin and NF-Kβ inhibitors increase TRAIL/Apo2L expression in MM cells, but not in normal B cells, which suggests the targeting of TRAIL/Apo2L as a novel therapeutic strategy in MM ( 104 ).…”

“…Accordingly, MM cells are highly sensitive to PIs such as bortezomib, which inhibits proteasome activity and results in increased levels of misfolded protein in the ER, in turn inducing apoptosis in malignant cells ( 126 ). Gambella et al., demonstrated a correlation between higher levels of X-box binding protein 1 (XBP1) and a higher sensitivity to bortezomib ( 104 ). Nikesitch et al., showed correlations between ER size, decreased levels of the UPR regulator ATF6, the reduced expression of XBP1 activator, and bortezomib resistance.…”

Pharmacokinetic characterization, benefits and barriers of subcutaneous administration of monoclonal antibodies in oncology

“…A study was already conducted to prove that health care professionals spend less time with the patient. 44 Another example of a mAb is denosumab which is only available for SC administration. Although the primary indication for this drug is osteoporosis, it is also approved for giant cell bone tumour in the higher available dose of 120 mg (Table 1).…”