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EHA 2021 | MRD evaluation during ixazomib maintenance in myeloma

Bruno Paiva, PhD, University of Navarra, Pamplona, Spain, discusses the importance of measurable residual disease (MRD) in the treatment of multiple myeloma commenting on data from the maintenance portion of the Phase III TOURMALINE-MM3 trial (NCT02181413) and the Phase III TOURMALINE-MM4 trial (NCT02312258) which both randomized patients with myeloma to receive either ixazomib or placebo maintenance. Dr Paiva reports that MRD assessment prior to maintenance is prognostically relevant, and that the prognostic value or MRD is enhanced by measuring MRD throughout maintenance treatment as serial MRD assessments enable detection of patients who convert to MRD-positive or MRD-negative during maintenance. This monitoring means that relapse can be anticipated, which can guide treatment decisions. This interview took place at the virtual European Hematology Association (EHA) Congress 2021.

Transcript (edited for clarity)

At EHA, I am pleased to present data on behalf of my co-authors on which may represent the largest dataset with MRD data collected during maintenance in the Phase III randomized clinical trials TOURMALINE-MM3 and MM4, which randomized either transplant-eligible as well as non-transplant candidates, to receive oral ixazomib or a placebo for up to two years as a maintenance strategy.

Our results, I believe are important as they provide three or four key messages...

At EHA, I am pleased to present data on behalf of my co-authors on which may represent the largest dataset with MRD data collected during maintenance in the Phase III randomized clinical trials TOURMALINE-MM3 and MM4, which randomized either transplant-eligible as well as non-transplant candidates, to receive oral ixazomib or a placebo for up to two years as a maintenance strategy.

Our results, I believe are important as they provide three or four key messages. Number one is the confirmation that MRD assessment prior to maintenance is prognostically relevant. Number two, that the prognostic value of MRD assessment is enhanced by measuring throughout maintenance. And MRD genetics are much more powerful in stratifying risk. And this is because patients that convert from MRD-positive to negative, have favorable outcome, similar to those with sustained negative MRD.

On the contrary, patients that convert from MRD-negative to positive, have clearly inferior PFS, almost similar to those patients with persistent MRD throughout maintenance. Therefore, the appearance of MRD, as well as persistent MRD emerged during maintenance as high-risk features that could warrant individualized treatment approaches.

In this regard, ixazomib shown to be of benefit when compared to placebo in similar patient populations, particularly those associated with MRD reappearance, as well as persistent MRD. Collectively, this study clearly demonstrates the value of MRD genetics throughout maintenance. And more importantly, that achieving or sustaining negative MRD should be considered as an endpoint also of maintenance treatment.

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