C. Ola Landgren, Leader of Translational and Clinical Oncology Program/Experimental Therapeutics at Sylvester Comprehensive Cancer Center, shared on LinkedIn:
“The future of cancer drug development is arriving faster, and minimal residual disease (MRD) is helping lead the way!
The scientific journey began in 2009 at the National Cancer Institute (NCI) with a simple observation: increasingly effective therapies were allowing more patients with multiple myeloma to achieve remission, yet many eventually relapsed. If conventional tests could no longer detect disease, the next step was clear. We needed more sensitive tools to identify the residual cancer cells responsible for future recurrence.
That vision led to the EVIDENCE meta-analysis and, subsequently, the creation of i2TEAMM by International Myeloma Foundation in 2012. Working in parallel, these international collaborations assembled patient-level data from randomized trials across newly diagnosed and relapsed/refractory myeloma.
The findings were remarkably consistent. MRD negativity at a sensitivity of at least 10⁻⁵, measured by next-generation sequencing or multicolor flow cytometry, was strongly associated with improved progression-free and overall survival across major patient populations.
After independently validating the analyses, the FDA presented the evidence to the Oncologic Drugs Advisory Committee in April 2024. The committee voted unanimously that MRD negativity could serve as an early endpoint to support accelerated approval in myeloma.
This was a landmark moment, but also the beginning of something much larger. Traditional trials in newly diagnosed myeloma may require 10-15 years to generate mature progression-free survival data. MRD can be assessed approximately one year after randomization, potentially producing the evidence needed to support accelerated approval within a few years of trial initiation.
That difference can bring promising therapies to patients many years earlier, make innovative clinical trials more feasible, and sustain investment in developing the next generation of treatments. Accelerated approval must still be followed by confirmation of long-term clinical benefit.
And the opportunity now extends far beyond myeloma. The next frontier is to develop and validate MRD endpoints across hematologic malignancies and solid tumors, integrate blood-based assays and advanced imaging, and move from using MRD only as a regulatory endpoint to using it as a real-time guide for precision medicine.
Imagine a future in which treatment intensity can be increased, reduced, changed, or discontinued according to each patient’s residual disease, delivering the right therapy, at the right intensity, for the right duration.
Myeloma has provided the proof of concept. The next chapter is pan-cancer.”
Other articles about Myeloma on OncoDaily.