Minimal residual disease is potential early outcome measure in myeloma
Meta-analysis data show cancer cell measure may be used as trial endpoint
Minimal residual disease or MRD — defined as a very small number of cancer cells that remain in the body during or after treatment — may be used as an early outcome measure or endpoint in clinical trials testing multiple myeloma therapies, new data from a meta-analysis study suggests.
According to the researchers, the use of MRD negativity as a proxy of clinical response, combined with lessons on timing, collaboration, and data sharing, may allow for shorter testing times and a faster roadmap to approval for cancer therapies.
With survival as an endpoint, the team noted, it can take years to show how well a treatment works before it can be approved.
Data from that meta-analysis, dubbed EVIDENCE — which stands for Evaluating Minimal Residual Disease as an Intermediate Clinical Endpoint for Multiple Myeloma — supported last year’s unanimous vote by a U.S. Food and Drug Administration (FDA) committee in favor of adopting MRD negativity as an endpoint likely to predict longer survival.
In a newly published review, C. Ola Landgren, MD, PhD, of the Sylvester Myeloma Research Institute at the University of Miami in Florida, and Sean M. Devlin, PhD, of Memorial Sloan Kettering Cancer Center in New York City, outline how EVIDENCE, which combined data from more than 12 clinical trials involving more than 6,000 patients, influenced the voting.
“The acceptance of MRD-negative complete response as an endpoint that is reasonably likely to predict clinical benefit will allow for the design of streamlined clinical trials for accelerated approval, enabling significantly faster patient access to novel therapies,” the researchers wrote.
The review, titled “Minimal Residual Disease as an Early Endpoint for Accelerated Drug Approval in Myeloma: A Roadmap,” was published in the journal Blood Cancer Discovery.
FDA committee adopted minimal residual disease as endpoint last year
Using MRD as an endpoint will make clinical trials faster and more efficient, giving patients quicker access to new treatments, according to the researchers.
They noted that achieving this required teamwork among researchers, pharmaceutical companies, and the FDA to gather and analyze data from many trials, even with limited resources.
This change addresses a growing challenge in multiple myeloma research: While existing treatments help patients live longer, it has become harder for new treatments to prove they are better using traditional clinical endpoints.
Drug approval will now happen much faster [for multiple myeloma]. … It’s an exciting time.
MRD offers a quicker way to measure treatment response, allowing smaller, shorter trials, the data showed.
“Drug approval will now happen much faster” for multiple myeloma, Landgren said in a university press release.
MRD is already being added to multiple myeloma clinical trials, and companies are working on better tools to measure it. Saying “it’s an exciting time,” Landgren noted that these changes mean doctors can know sooner how well new treatments are working.
In the vote last year, the FDA’s Oncologic Drugs Advisory Committee adopted MRD negativity 12-0 as a clinical trial endpoint.
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