IMROZ post hoc analysis: MRD dynamics with Isa‑VRd/Isa‑Rd for TI‑NDMM

A post hoc analysis of the phase III IMROZ study (NCT03319667) evaluated measurable residual disease (MRD) dynamics by next-generation sequencing in previously untreated, transplant-ineligible (TI) patients with newly diagnosed multiple myeloma (NDMM) treated with isatuximab + bortezomib + lenalidomide + dexamethasone (Isa‑VRd) induction followed by Isa‑Rd maintenance or VRd followed by Rd. The analysis included 361 evaluable patients (Isa‑VRd/Isa‑Rd, n = 223; VRd/Rd, n = 138). Results were published in Blood by Orlowski et al.

Key data: Isa‑VRd/Isa‑Rd maintained higher MRD-negativity rates (10⁻⁵) than VRd/Rd over time (76.1% vs 40.0% at 60 months; odds ratio [OR], 4.59; 95% confidence interval [CI], 1.34–17.04). Among patients MRD-negative at induction, fewer converted to MRD-positive during maintenance with Isa‑VRd/Isa‑Rd vs VRd/Rd (5.6% vs 26.9% at 24 months; 12.3% vs 34.8% at 36 months). Among patients who converted from MRD-negative to MRD-positive at any timepoint, time to progression favored Isa‑VRd/Isa‑Rd (hazard ratio [HR], 0.275; 95% CI, 0.114–0.664; p = 0.0041).

Key learning: Higher rates of MRD negativity and lower rates of conversion from MRD-negative to MRD-positive were observed with Isa‑VRd/Isa‑Rd than VRd/Rd in TI‑NDMM, supporting its use as a standard-of-care first-line treatment option in this setting.