The study chair for this trial is Shaji Kumar, MD (Mayo Clinic). The study co-chairs are Ajay Nooka, MD, MPH (Emory University/Winship Cancer Institute), Lale Kostakoglu, MD, MPH (University of Virginia/UVA Cancer Center), and Matthias Weiss, MD (Mayo Clinic – Franciscan Healthcare).
In current practice, transplant-eligible myeloma patients undergo a single autologous stem cell transplant followed by maintenance therapy with the immunomodulatory agent lenalidomide, administered orally. The median progression-free survival (PFS) with this approach, particularly with indefinite maintenance therapy, is about four years. In the subset of patients who have measurable or minimal residual disease (MRD) remaining in the body following maintenance treatment, researchers in the ECOG-ACRIN Myeloma Committee hypothesize that survival may be improved by escalating treatment with the addition of ixazomib, an oral proteasome inhibitor.
EAA171/OPTIMUM is a randomized phase III trial for patients who were previously diagnosed with multiple myeloma, have received an autologous stem cell transplant, and have completed approximately one year of lenalidomide maintenance therapy. Patients with these characteristics may enter Step 0 for MRD analysis, determined by either central MRD assessment at Mayo Clinic or local immunofixation test results.
The study’s primary objective is to determine if the addition of ixazomib to lenalidomide improves overall survival. Patients screened as MRD-positive will enter Step 1 and be randomized 1:1 to continue therapy either with lenalidomide plus ixazomib or lenalidomide plus placebo. Both groups will continue treatment until disease progression or unacceptable toxicity.
The ixazomib-lenalidomide combination is FDA-approved for the treatment of patients with relapsed myeloma. The combination was studied as post-transplant maintenance in a phase II trial by investigators at MD Anderson, and the results point toward this regimen being effective and well tolerated in this setting. The oral nature of the two medications is convenient for patients—plus, it allows for a blinded, placebo-controlled trial to make a true estimate of the impact of therapy escalation on quality of life and patient-reported outcomes.
The secondary imaging endpoints of this trial center on assessing the prognostic impact of PET-positive lesions, identified by 18F-FDG PET/CT. A comparison between arms should provide data on how that status may be impacted by the randomized intervention.
Evaluation of overall survival benefit for escalating therapy in patients with persistent MRD will immediately make the results of the OPTIMUM study highly relevant for clinical practice. Positive results would transform MRD assessment from its current status as a powerful prognostic factor for myeloma patients—to an important tool in clinical practice. The fundamental question that this trial is designed to address can be stated very clearly: Does escalating therapy based on the MRD positive status after a defined duration of therapy alter the outcomes in patients with myeloma?
Learn more about EAA171/OPTIMUM at ecog-acrin.org.