Source: Myeloma – Hematology Advisor
In transplant-eligible patients with newly diagnosed multiple myeloma (MM), a recent study identified factors related to whether measurable residual disease (MRD) negativity was sustained over time. Study results were reported in the journal Blood.
The study was a retrospective analysis of data obtained from the FORTE trial (ClinicalTrials.gov Identifier: NCT02203643), which enrolled transplant-eligible patients with newly diagnosed MM.
In this analysis, the researchers evaluated data from the study to identify possible factors associated with losing MRD negativity over time. This analysis had a primary endpoint of the cumulative incidence of MRD resurgence or progressive disease after MRD negativity was initially established.
MRD negativity was characterized through the use of multiparametric flow cytometry, with a sensitivity of 10-5. MRD was assessed at the time of suspected complete response, at premaintenance in patients with a very good partial response or better, and at 6-month intervals during maintenance.
There were 474 patients enrolled, of whom 310 (65%) reached MRD negativity. Among those with MRD negativity, 306 patients were included in further analyses. Patients had a median time to first MRD negativity of 8.9 months.
With a median follow-up of 50.4 months after MRD negativity was demonstrated, there were 185 patients (60%) who continued to have MRD negativity and progression-free status. However, there were 118 patients (39%) who had lost MRD-negative status, and 3 patients (1%) died but had not experienced disease progression.
Among the 118 patients in whom MRD negativity was not sustained, MRD positivity was observed in bone marrow prior to the onset of progressive disease in 70 patients (59%). Criteria for progressive disease were met before detection of bone marrow MRD positivity in 48 patients (41%).
A greater risk of unsustained MRD negativity appeared significantly associated with multiple factors. These included the presence of 1q amplification (hazard ratio [HR], 2.07; 95% CI, 1.12-3.82; P =.02), having 2 or more high-risk cytogenetic abnormalities rather than 0 (HR, 2.22; 95% CI, 1.33-3.71; P =.0024), a high baseline level of circulating tumor cells (HR, 1.86; 95% CI, 1.17-2.96; P =.008), and a time to first MRD negativity occurring after the start of consolidation rather than preconsolidation (HR, 1.56; 95% CI, 1.04-2.32; P =.029).
A factor associated with a lower risk of unsustained MRD negativity was the use of carfilzomib combined with lenalidomide during the first 2 years of maintenance therapy, compared with receiving lenalidomide alone (HR, 0.58; 95% CI, 0.35-0.96; P =.033).
“The results of our analysis, limited by the number of patients and the retrospective nature, should be validated in larger prospective cohorts of patients, including daratumumab-based combinations and new immune therapies,” the researchers wrote in their report.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.