medwireNews: Post-treatment minimal residual disease (MRD) status can serve as a marker of long-term survival in patients with newly diagnosed multiple myeloma, shows a meta-analysis.
These findings confirm those of earlier “small-to-medium-sized” studies suggesting an association between MRD negativity and longer progression-free and overall survival (PFS, OS), say the researchers, adding that the analysis provides “quantitative evidence to support the integration of MRD assessment as an end point in clinical trials of [multiple myeloma].”
They pooled data from 21 studies reporting on the impact of MRD status – as assessed by any method with a limit of detection of at least 0.01% – on survival outcomes in patients who had received any treatment other than allogeneic stem cell transplantation for newly diagnosed multiple myeloma. Fourteen studies provided information on PFS while 12 reported on OS; the total number of included participants was 1273 and 1100, respectively.
PFS was a median of 54 months for patients who were MRD negative after treatment and 26 months for those who remained MRD positive, equating to a significant hazard ratio (HR) of 0.41.
The corresponding median OS times were 98 and 82 months, also a significant difference, giving an HR of 0.57.
The investigators, led by Nikhil Munshi (Dana-Farber Cancer Institute, Boston, Massachusetts, USA), observed similar results when they restricted the analysis to studies that provided information on complete response rates.
Specifically, in patients who attained a complete response, the absence versus presence of MRD was associated with a significantly longer PFS and OS, with respective HRs of 0.44 and 0.47, they write in JAMA Oncology.
Highlighting that the association between MRD status and outcomes was irrespective of the treatment used or the method used to detect MRD, Munshi et al conclude that their results “support the conceptual basis for integrating MRD assessment into the treatment of [multiple myeloma].”
Writing in an associated editorial, Nicole Gormley (US Food and Drug Administration, Silver Spring, Maryland, USA) and colleagues applaud the study authors for taking this “considerable first step” towards elucidating the prognostic role of MRD and its potential as a surrogate endpoint.
However, they believe that many unanswered questions remain – such as, the MRD level threshold that correlates best with clinical benefit, the ability of MRD to predict responses in a relapsed or refractory setting, and the appropriate timing of MRD evaluation.
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