MRD Conversion During Maintenance Predicts Progression-Free Survival in Myeloma

Among patients with multiple myeloma (MM), conversion of minimal residual disease (MRD) status during maintenance appears to affect the risk of disease progression, according to research published in Blood.

Although MRD status during continuous therapy among patients with relapsed or transplant-ineligible MM is effective at predicting clinical outcomes, whether this prognostic tool is useful among patients undergoing maintenance therapy has not been firmly established.

Ixazomib has previously been evaluated as a maintenance therapy among patients with transplant-eligible or -ineligible disease; 2 phase 3 randomized trials explored its safety and efficacy compared with placebo. For this pooled analysis, researchers evaluated data from these trials to determine the prognostic significance of MRD status and conversion among patients with MM.

Overall, data from 1280 patients with MM were included. The pooled data were taken from the phase 3 TOURMALINE-MM3 and TOURMALINE -MM4 trials (ClinicalTrials.gov Identifiers: NCT02181413 and NCT02312258, respectively), which were placebo-controlled studies evaluating 2-year ixazomib maintenance.

Analysis showed that, at randomization, MRD status was independently prognostically significant, with a median progression-free survival (PFS) of 38.6 months among patients with MRD-negative status vs 15.6 months among patients with MRD-positive status (hazard ratio, 0.47).

At 14 months of maintenance therapy, regardless of group allocation, prolonged PFS was noted among patients who converted from  MRD-positive to MRD-negative (2-year PFS rate, 76.8% vs 27.6% among patients with persistent  MRD-positive status). Similarly, patients with sustained M MRD-negative status had improved 2-year PFS rates compared with those who converted from MRD-negative to MRD-positive (75.0% vs 34.2%, respectively).

The authors noted, furthermore, that the 28-month landmark analysis yielded similar results. Ixazomib maintenance also appeared to improve PFS among patients who had MRD-positive status at randomization (hazard ratio, 0.65).

“Importantly, our results highlight that MRD-directed therapy should rely on MRD dynamics rather than MRD status assessed at a single time point,” the authors noted in their report. “Thus, our study sets the stage for serial MRD monitoring during maintenance or observation in clinical trials.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference

Paiva B, Manrique I, Dimopoulos MA, et al. MRD dynamics during maintenance for improved prognostication of 1280 patients with myeloma in the TOURMALINE-MM3 and -MM4 trials. Blood. 2023;141(6):579-591. doi:10.1182/blood.2022016782

This article originally appeared on Hematology Advisor