Subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma (COLUMBA): a multicentre, open-label, non-inferiority, randomised, phase 3 trial
- Study type
- Clinical trial
- Study name
- COLUMBA
- Phase
- Phase 3
- Design
- Multicentre (147 centres in 18 countries), open-label, non-inferiority, randomised trial; ongoing
- Sample size
- 522 patients (263 in the subcutaneous group and 259 in the intravenous group)
- Source
- The Lancet Haematology · 2020
- Trial registration
- NCT03277105
In plain words
Daratumumab is a medicine for multiple myeloma that is usually given as a long infusion into a vein. In this study, an injection of the drug under the skin was compared with the infusion into a vein in patients whose disease had come back or had not responded to previous treatments. The injection under the skin was no less effective, and gave no lower drug levels in the blood, than the vein method, and according to the researchers' conclusions it was safer.
Key results
Treatment arms and regimens
Subcutaneous daratumumab 1800 mg, co-formulated with recombinant human hyaluronidase PH20 at 2000 U/mL; weekly (cycles 1 and 2), every 2 weeks (cycles 3 to 6) and then every 4 weeks (28-day cycles) until disease progression or toxicity.
Intravenous daratumumab 16 mg per kg body weight; weekly (cycles 1 and 2), every 2 weeks (cycles 3 to 6) and then every 4 weeks (28-day cycles) until disease progression or toxicity.
Source of the regimen details: Abstract of the paper
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Adult patients (aged 18 years or older) with relapsed or refractory multiple myeloma confirmed according to International Myeloma Working Group (IMWG) criteria, who had received at least three previous lines of therapy including a proteasome inhibitor and an immunomodulatory drug or were double-refractory to both drug classes (proteasome inhibitor and immunomodulatory drug), and who had an ECOG performance status score of 2 or less.
Endpoints
Co-primary endpoints: overall response and maximum trough concentration (Ctrough; cycle 3, day 1, pre-dose). The non-inferiority margin for overall response was defined by retaining 60% of the lower bound (20.8%) of the 95% CI of the SIRIUS trial. Efficacy analyses were in the intention-to-treat population. The pharmacokinetic-evaluable population comprised patients who received all eight weekly daratumumab doses in cycles 1 and 2 and provided a pre-dose pharmacokinetic blood sample on day 1 of cycle 3. The safety population comprised all patients who received at least one dose of daratumumab.
Safety and side effects
The most common grade 3 and 4 adverse events in the subcutaneous group (260 patients evaluable for safety) versus the intravenous group (258 patients) were anaemia (13% versus 14%), neutropenia (13% versus 8%) and thrombocytopenia (14% versus 14%). Pneumonia was the only serious adverse event with a frequency above 2% (7 patients [3%] in the subcutaneous group and 11 patients [4%] in the intravenous group). One death from a treatment-related adverse event occurred in the subcutaneous group (febrile neutropenia) and 4 deaths in the intravenous group (sepsis [2], hepatitis B reactivation [1] and Pneumocystis jirovecii pneumonia [1]). Three patients in the subcutaneous group and one patient in the intravenous group did not receive treatment and were not evaluable for safety.
Clinical significance and place in guidelines
This trial showed that subcutaneous daratumumab is non-inferior to the intravenous form in efficacy and pharmacokinetics and has a better safety profile. The authors state that these data could support regulatory approval of the subcutaneous formulation. Approval status and its place in clinical guidelines should be checked separately, as the abstract does not address them.
Limitations
The study is open-label. The analysis was reported at a short median follow-up of 7.5 months and the trial is still ongoing. The non-inferiority criterion was defined by retaining part of the effect of the SIRIUS trial. This abstract gives no data on progression-free or overall survival.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.