Evaluating Maintenance In Light chain Amyloidosis (EMILIA) - PROJECT SUMMARY/ABSTRACT Light chain (AL) amyloidosis is a rare plasma cell disorder. It is caused by abnormal misfolding of monoclonal immunoglobulin light chains causing extracellular deposition of amyloid, which ultimately results in organ dysfunction and death. The treatment goal in AL amyloidosis is elimination of the production of the amyloidogenic light chains by means of anti-plasma cell therapies, which can allow for organ recovery and extended survival. The phase III randomized ANDROMEDA study, which showed superiority of daratumumab- CyBorD over CyBorD induction in the rate of complete hematological response and overall hematological response rate, established the standard of care for newly diagnosed AL amyloidosis as daratumumab-CyBorD. However, the study continued with daratumumab maintenance for up to 18 cycles in those receiving daratumumab-CyBorD induction, in a non-randomized manner, thus providing no proof of the need for maintenance therapy in this disease or for its optimal duration. Our main objective in this study is to assess the optimal duration of maintenance in the post-Andromeda era. The proposed study is a phase II randomized study where patients achieving adequate hematological response to daratumumab-CyBorD induction will be randomized in a 1:1 ratio to single agent daratumumab maintenance of 6 months (experimental arm), versus 18 months of daratumumab maintenance (control arm). The study will have a pragmatic trail design with the use of broadened eligibility criteria to allow participants at different stages of the disease to take part. In Aim 1, the primary assessment of efficacy will be event-free survival (EFS). In Aim 2, we will assess secondary efficacy endpoints including hematological response; measurable residual disease (MRD) assessed by next generation multiparametric flow cytometry; depth of organ response; adverse events (especially infections and IVIG use); time to next therapy, and overall survival. In Aim 3 we will assess patient-reported quality of life assessed in a longitudinal manner throughout maintenance and after maintenance completion using the PROMIS29 questionnaire and selected items from the PRO-CTCAE questionnaire. The study will be conducted at Mayo Clinic campuses in Arizona, Florida, and Minnesota with 96 patients planned to be accrued to meet the statistical design for a non-inferiority study. The study’s key strength is its design as a pragmatic trial, thus reflecting real world practice. As part of that, we will allow treatment by the local medical doctor with interval visits to the Mayo Clinic campus for efficacy and safety assessments. We bring a research alliance in plasma cell disorders between the three Mayo Clinic campuses. Lastly, MRD testing and quality of life assessment are innovative tools in clinical research in AL amyloidosis, and will be assessed longitudinally in this study.
