A study on the value of courtesy of multiple myeloma (MM) patients treated with Ninraro (ixazomib), a second-generation oral proteasome inhibitor (PI) developed by Takeda, evaluated at a single time point. Periodic evaluation of MRD dynamics has been shown to show better prognostic value than measurable residual disease (MRD) status.
The results of a study investigating the prognostic value of MRD changes from the combined cohorts of Ninraro’s TOURMALINE-MM3 and TOURMALINE-MM4 clinical trials were published in Blood, the journal of the American Society of Hematology, on the 9th (local time).
The TOURMALINE-MM3 and TOURMALINE-MM4 studies were phase 3 clinical trials evaluating single maintenance therapy with Ninra versus placebo in patients with newly diagnosed multiple myeloma eligible or ineligible for transplantation.
In this clinical trial, researchers evaluated the MRD status at the time of ‘random assignment’, ’13 cycles of treatment’, and ‘end of treatment’ through bone marrow aspirates of participants (2,077) who showed complete response (CR). The final analysis included bone marrow aspirate analyzes from a total of 1,280 patients.
As a result of the analysis, the median progression-free survival (mPFS) was 38.6 months in MRD-negative patients at the time of randomization, which was longer than 15.6 months in MRD-positive patients. In addition, prolongation of PFS in these MRD-negative patients was consistent in most subgroups irrespective of demographics, disease characteristics at diagnosis (cytogenetic risk, previous therapy, previous response, etc.), and geographical area of MRD testing.
A total of 1,226 patient data were available during the Ninlaro or placebo treatment period, and 1,166 patients were included in the evaluation of MRD change.
The researchers found that MRD changes in the maintenance phase provided greater risk stratification than MRD status.
A landmark analysis at 14 months showed a prolonged PFS in patients who switched from MRD-positive to negative status (2-year PFS 76.8%) compared to patients with persistent MRD-positive status (2-year PFS 27.6%).
In addition, a longer PFS was observed in patients who remained MRD-negative (2-year PFS 75.0%) compared to patients who switched from MRD-negative to positive (2-year PFS 34.2%), which was similar to the 28-month landmark analysis. showed
Compared with placebo, maintenance therapy with Ninlaro improved PFS in MRD-positive patients at randomization (mPFS 18.8 months versus 11.6 months) or at 14-month analysis (mPFS 16.8 months versus 10.6 months). There was no difference in MRD-negative patients.
“Patients included in the analysis are the largest multiple myeloma population ever reported, undergoing annual MRD evaluations during the maintenance period,” said the authors. By doing so, we demonstrated that single-point MRD evaluation has limited prognostic value.”
“This shows that MRD-negative status is a reliable endpoint during the maintenance therapy phase, and that there is an increased risk of disease progression in patients whose MRD status transitions from negative to positive,” the researchers added.
