The trial was a randomised, double-blind, placebo-controlled study that compared maintenance after transplant with ixazomib, that is an oral proteasome inhibitor, given up to two years versus treatment with placebo. The trial enrolled patients younger than 60, patients eligible for high dose chemotherapy and transplant that received an induction with proteasome inhibitors and/or immunomodulatory agents and then a single transplant.
How many patients?
About 650 patients were enrolled in the study. We found that maintenance with ixazomib significantly improved the progression free survival with a median overall improvement in progression free survival from 21 months with placebo up to 26.5 months with ixazomib and overall a 39% improvement in PFS with a hazard ratio of 0.72 in favour of ixazomib. We also saw that the advantage in PFS was retained in most of the subgroup of patients analysed, including patients with high risk disease that represents an unmet medical need.
We also see that the advantage was present in patients MRD positive at the beginning of the study before the entrance as well as in patients MRD negative. With patients MRD negative at the beginning of the study that received ixazomib maintenance that achieved a median PFS around 38 months.
Treatment was very well tolerated with only 7% of patients that had to discontinue for toxicity and the rate was comparable to the rate of discontinuation in the placebo arm. The main adverse events were thrombocytopenia or gastrointestinal events, mainly nausea, diarrhoea and vomiting, but most of these events were mild, grade 1/2, and were manageable. There was no increase in second primary malignancies.
What is the message for doctors?
I think the message is that this trial that is the first double-blind, randomised, placebo-controlled trial evaluating a proteasome inhibitor oral maintenance in the myeloma setting shows that ixazomib can be another option for the maintenance treatment of patients after transplant.