Results of a phase 3 study of daratumumab monotherapy administered subcutaneously (SC) compared with intravenous (IV) administration in patients with relapsed/refractory multiple myeloma (R/R MM) showed no significant differences in efficacy or pharmacokinetic end points. The findings of this study were presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.1
Daratumumab is a monoclonal antibody that targets CD38, a glycoprotein expressed on the surface of different types of cells, including malignant plasma cells in multiple myeloma and many types of immune cells. It is believed to inhibit the growth of multiple myeloma cells through induction of antibody-dependent cell-mediated toxicity, and immune-mediated cell lysis, as well as other mechanisms of action.2
The IV formulation of daratumumab has been approved by the US Food and Drug Administration (FDA) as either monotherapy or in combination with standard-of-care regimens for patients with R/R MM, or when combined with bortezomib/melphalan/dexamethasone for transplant-ineligible, newly diagnosed patients with multiple myeloma.2 However, IV daratumuab is typically infused over hours, and is associated with infusion reactions in a substantial percentage of patients.
In the open-label, multicenter, phase 3 COLUMBA trial (ClinicalTrials.gov Identifier: NCT03277105), 522 adult patients with R/R MM were randomly assigned in a 1:1 ratio to receive an SC formulation of daratumumab (including recombinant human hyaluronidase to temporarily break down the hyaluronan barrier to allow for the more rapid administration of large volumes of drug). The formulation was a fixed dose of 1800 mg once weekly in cycles 1 and 2, every 2 weeks in cycles 3 to 6, and every 4 weeks in cycle 7 and beyond, with each cycle lasting 4 weeks, and administered using alternating left/right abdominal site injections. This was compared with the IV formulation (16 mg/kg once weekly in cycle 1 and 2, every 2 weeks in cycle 3 to 6, and every 4 weeks in cycle 7 and beyond).
The coprimary end points of the study were overall response rate and the maximum pre-dose trough concentration of daratumumab on day 1 of cycle 3, with both end points analyzed for noninferiority.
Patient- and disease-related characteristics of the study population included a median age of 67 years, a median of 4 previous lines of therapy, as well as prior treatment with both an immunomodulatory drug and a proteasome inhibitor in all patients.
At a median follow-up of 7.5 months, the overall response rates were 41.1% and 37.1% for patients receiving SC and IV formulations, respectively. In addition, the ratio of the maximum pre-dose trough concentration of daratumumab on day 1 of cycle 3 for SC daratumumab over IV daratumumab was 108%. Furthermore, median PFS was 5.6 months versus 6.1 months for patients receiving the SC and IV formulations of daratumumab, respectively (P =.9258).
Anemia, neutropenia, thrombocytopenia, and diarrhea were the most common treatment-emergent adverse events reported in the study. There with generally comparable safety profiles for the 2 study arms, although rates of grade 3/4 neutropenia were slightly higher for patients receiving SC daratumumab (13%) compared with IV daratumumab (8%). The rates of treatment discontinuation due to an adverse event were 7% and 8% for those receiving SC and IV daratumumab, respectively.
While 34.5% of patients receiving IV daratumumab experienced infusion reactions, these were reported in only 12.7% of those receiving SC daratumumab. Injection-site reactions occurred in approximately 7% of patients receiving SC daratumumab.
Importantly, the median duration of injection for SC daratumumab was 5 minutes compared with infusion times of 421 minutes, 255 minutes, and 205 minutes for patients receiving the first, second, and subsequent infusions of IV daratumumab.
A striking difference was noted in assessments of treatment satisfaction over time of patients in the 2 study arms, showing higher levels of satisfaction with treatment for patients receiving SC daratumumab compared with IV daratumumab.
In her concluding remarks, Dr Mateos noted that “these results support the use of flat-dose 1800 mg daratumumab SC, which is comparable to daratumumab IV.”
- Mateos M-V, Nahi H, Legiec W, et al. Efficacy and safety of the randomized, open-label, non-inferiority, phase 3 study of subcutaneous (SC) versus intravenous (IV) daratumumab (DARA) administration in patients (pts) with relapsed or refractory multiple myeloma (RRMM): COLUMBA. Presented at: 2019 American Society of Clinical Oncology (ASCO) Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract 8005.
- Daratumumab (Darzalex®) (package insert]. Horsham, PA: Janssen Biotech, Inc.; 2019.
This article originally appeared on Cancer Therapy Advisor