EHA2021: MRD Negativity as Myeloma Treatment Endpoint for Maintenance Therapy
Posted: Thursday, July 1, 2021
Utilizing measurable residual disease (MRD) kinetics during treatment for multiple myeloma enhances the prognostic value of MRD status at the beginning of maintenance therapy. The achievement and sustainability of MRD negativity can be used as a treatment endpoint in the maintenance setting, according to Bruno Paiva, PhD, of the Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain. This analysis was presented during the European Hematology Association (Virtual Congress (EHA2021; Abstract S184).
Researchers performed a pooled analysis of the phase III TOURMALINE-MM3 and -MM4 trials. Patients with a partial response or better after proteasome inhibitor and/or immunomodulatory drug induction plus single bone marrow transplant (MM3) or 6 to 12 months of standard-of-care induction therapy (MM4) were included in the study. Patients were randomly assigned 3:2 to receive 3 mg of oral ixazomib maintenance therapy or placebo for up to 2 years. Bone marrow aspirates were collected from 2,077 patients in complete response or very good partial response at screening, halfway through therapy, at the end of treatment or at the time of new suspected complete response and assessed for MRD status.
MRD status was available for 1,280 patients at screening; 262 patients achieved MRD negativity and 1,018 were MRD-positive. Those who were MRD-positive at the beginning of maintenance therapy saw a significant progression-free survival benefit with ixazomib therapy (18.8 months) compared with placebo (11.6 months, P < .001).
MRD negativity was sustained by 10% of patients, whereas 5% converted from MRD positivity to MRD negativity, 10% converted from MRD negativity to MRD positivity, and 75% had persistently positive MRD. Progression-free survival has not yet been reached among patients converting from MRD positivity to MRD negativity during maintenance therapy. In comparison, progression-free survival was 23.1 months among patients converting from MRD negativity to MRD positivity and 14.1 months for those remaining MRD-positive. Failure to achieve MRD status after screening resulted in an eightfold higher risk of disease progression or death in this cohort (hazard ratio = 8.20).
Disclosure: For full disclosures of the study authors, visit library.ehaweb.org.
