The PLEIADES study basically is a three arm study looking at the utilisation of daratumumab subcutaneous formulation in combination with other standard anti-myeloma regimens, in particular daratumumab with VRD in newly diagnosed transplant eligible, daratumumab with VMP in newly diagnosed transplant ineligible and daratumumab RD for relapsed disease.
Would you be able to explain the trial design?
This is a phase II where we know that the dose of daratumumab subcutaneous is 1,800mg flat dosing. It was given in combination with the approved backbone regimens, so VRD in the US particularly, VMP as in the ALCYONE study and RD as in the POLLUX study. So it’s essentially the subcutaneous version of the intravenous daratumumab based formulations.
What were the main results of the endpoints that were assessed?
The primary endpoint was greater than VGPR for the DVRD and the overall response rate for the other two studies. So what we found is that all of those endpoints were comparable so the conversion of daratumumab from IV to subcutaneous still yields comparable efficacy compared to the known daratumumab IV formulations with the same backbone regimens.
Were any adverse events observed?
An important secondary endpoint was really pharmacokinetics and adverse events/infusion related reactions. The pharmacokinetics were comparable between the daratumumab subcutaneous and IV studies, historical comparison. Then the infusion related reactions were quite interesting because the infusion related reactions in PLEIADES across all subjects in all three cohorts was only 7.5% which is the lowest of published daratumumab studies to date and highlights the safety of the subcutaneous formulation. Importantly, most of those infusion related reactions were grade 1/2, approximately 93%, and 93% were also during the first infusion. So what’s important about this study is that we have what we look for in medicine which is you have comparable efficacy, better safety and, most importantly for patients, convenience going from a median first infusion time of seven hours to five minutes. So it’s the holy grail of medicine to look for a drug that’s as efficacious, more convenient and more safe.
What’s next for the study?
This study there is another cohort with daratumumab subcutaneous in combination with carfilzomib. Currently the daratumumab subcutaneous formulation is under review by health authorities so we look forward to that approval. I think that will be great for patient convenience and wellbeing.