Posted: Friday, February 4, 2022
The addition of the oral proteasome inhibitor ixazomib to a maintenance regimen of lenalidomide and dexamethasone following autologous stem cell transplantation in patients with newly diagnosed multiple myeloma does not appear to improve outcomes, according to the results of the GEM2014MAIN trial presented at the 2021 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 466). “This could be partially explained by the higher toxicity leading to dose reductions or discontinuation of ixazomib in the [ixazomib/lenalidomide/dexamethasone] arm,” explained Laura Rosiñol, MD, PhD, of the IDIBAPS, Hospital Clínic, Barcelona, and colleagues.
In this study, patients with stable disease or better following an autologous hematopoietic stem cell transplantation were randomly assigned to receive maintenance therapy with either lenalidomide and dexamethasone (n = 161) or lenalidomide and dexamethasone plus ixazomib (n = 171). After 2 years of treatment, patients with negative minimal residual disease (MRD) discontinued maintenance therapy; for those with positive MRD, lenalidomide plus dexamethasone was continued for 3 additional years.
After a follow-up of 56 months, there was no difference in progression-free survival between the control arm and the ixazomib arm (63% vs. 62%). No significant differences in progression-free or overall survival were seen among patients with standard- versus high-risk cytogenetics.
For patients with standard cytogenetics who achieved MRD negativity at screening, significantly longer progression-free and overall survival were observed compared with patients with MRD positivity. Those with both high-risk cytogenetics and MRD positivity had a “dismal” prognosis compared with patients who achieved MRD negativity.
As for safety, grade 3 or 4 neutropenia was similar in the ixazomib and control arms (37% vs. 39%). However, the incidence of grade 3 or 4 thrombocytopenia (16% vs. 7%) and grade 3 or 4 gastrointestinal toxicity (15% vs. 2%) was significantly higher with the addition of ixazomib, and one-third of patients treated with ixazomib required dose reductions.
Disclosures: For full disclosures of the study authors, visit ash.confex.com.
2021 ASH Annual Meeting & Exposition