MRD negativity dynamics in the IMROZ study

Dr Robert Orlowski, a haematologist at the University of Texas MD Anderson Cancer Center in Houston, Texas, provided a comprehensive summary of his presentation on MRD testing in the context of the IMROZ trial. 

For transplant-ineligible NDMM patients, one of the most commonly used initial therapeutic regimens is VRd. The IMROZ trial was a randomised study comparing standard VRd induction therapy followed RD maintenance, with an experimental arm that incorporated isatuximab, an anti-CD38 monoclonal antibody, into the VRd regimen (Isa-VRd) during induction, followed by maintenance with Isa-RD. The primary results of the trial, published earlier this year, demonstrated superior outcomes for the isatuximab-containing quadruplet therapy. Specifically, the Isa-VRd regimen resulted in a higher CRR and improved PFS compared to the standard VRd regimen. Adverse events associated with isatuximab were consistent with those observed for other anti-CD38 antibodies, predominantly manifesting as increased cytopenias and infection risk.

At ASH, MRD data were presented, which provides one of the most sensitive measures of residual disease in MM. MRD negativity at a sensitivity threshold of 10⁻⁵ was achieved at a higher rate in the Isa-VRd group compared to the VRd group after the initial six months of therapy. Moreover, the proportion of patients achieving MRD negativity continued to increase with ongoing treatment. Patients achieving MRD negativity with Isa-VRd demonstrated longer PFS in subsequent therapies compared to those treated with VRd. This addresses prior concerns that frontline use of an anti-CD38 antibody might limit future treatment options or lead to more aggressive disease upon relapse. These results strongly support Isa-VRd as an optimal upfront therapy for transplant-ineligible NDMM patients.