Finding better, safer ways to administer drugs is an important part of cancer research. The use of monoclonal antibodies via subcutaneous (SC) administration has changed practice and has led to the question of whether this dosing route improves the safety and efficiency of administration. In the last issue of the Journal of Hematology Oncology Pharmacy, Kye and colleagues attempted to answer this question by looking at the results of their single-center experience with SC daratumumab.1
When given as an intravenous (IV) infusion, daratumumab, an anti-CD38 monoclonal antibody, has a high rate of infusion-related reactions (IRRs) as one of its drawbacks.2 The IRRs occur most frequently in the first cycle of treatment and less often in later cycles, which results in extended infusion times and an extended time in the infusion clinic.2 On the other hand, the SC administration of daratumumab has been associated with fewer IRRs than IV daratumumab3-5 and has led to a significant decrease in infusion center time.6 The study by Kye and colleagues examines the use of SC daratumumab at Stanford Health Care and quantifies the rate of IRRs with SC administration.1
In this study, 82 patients (33 of whom were daratumumab-naïve) who were receiving SC daratumumab were evaluated.1 IRRs were documented in 10% of the patients, all of which were grade 1 or 2. All but 1 of the 8 patients with an IRR were from the daratumumab-naïve group.
One concern with the SC administration of daratumumab is that IRRs may be delayed. Kye and colleagues defined a delayed reaction as more than 4 hours after the SC administration of daratumumab.1 According to this criterion, more than half of the IRRs in this study were delayed reactions, with a median onset of 6.4 hours (range, 0.25-24 hours). This creates a dilemma for clinicians regarding how much time is needed to observe patients after the SC administration of daratumumab. Based on the result of Kye and colleagues’ study, their institution adjusted its monitoring plan to an observation time of 1 hour after cycle 1 of treatment with daratumumab.1 They believed that this timing was reasonable because all of the study patients, except 1 patient who had a reaction just before the end of the 4-hour observation period, had immediate (onset of <15 minutes) or delayed (onset of >4 hours) reactions, all of which were mild and easily manageable in the outpatient setting.1
When conducting this type of retrospective study, it may be difficult to determine if the IRR being reported is a result of receiving the drug in question or another reason. The study by Kye and colleagues is no different, and the investigators mention in their limitations that the documentation of the IRR was needed for evaluation within the study. Any IRR that occurred that was not reported or documented was not included in the study results.1 Although this report includes a table that shows the reactions that are considered IRRs, it would have been helpful if they had listed which of the IRRs were delayed reactions.
The advantage of using SC daratumumab versus IV daratumumab is shown in the study by Kye and colleagues, which confirms the results of other studies.5,6 The safety advantage of SC daratumumab, decrease in chair time needed in the clinic, and expected improvement in patient satisfaction can result in a significant improvement in the delivery of daratumumab.
- Kye J, Patel S, Seyer M, et.al. Safety of SC daratumumab in the treatment of plasma-cell disorders: a single-center experience. J Hematol Oncol Pharm. 2023;13(2):65-70.
- Darzalex (daratumumab) injection, for intravenous use [prescribing information]. Janssen Biotech; January 2023. www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX-pi.pdf. Accessed April 27, 2023.
- Darzalex Faspro (daratumumab and hyaluronidase-fihj) injection, for subcutaneous use [prescribing information]. Janssen Biotech; November 2022. www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX+Faspro-pi.pdf. Accessed April 27, 2023.
- Mateos MV, Nahi H, Legiec W, et al. Subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma (COLUMBA): a multicentre, open-label, non-inferiority, randomised, phase 3 trial. Lancet Haematol. 2020;7:e370-e380. Erratum in: Lancet Haematol. 2020;7:e710.
- Usmani SZ, Nahi H, Legiec W, et al. Final analysis of the phase III non-inferiority COLUMBA study of subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma. Haematologica. 2022;107:2408-2417.
- Soefje SA, Carpenter C, Carlson K, et al. Clinical administration characteristics of subcutaneous and intravenous administration of daratumumab in patients with multiple myeloma at Mayo Clinic Infusion Centers. JCO Oncol Pract. 2023;19(4):e542-e549.