Cancer Research in the Wake of a Key FDA Decision on Minimal Residual Disease
Summary
- Cancer research is shifting after a key ruling at the FDA that was based on data from Sylvester researchers.
- An FDA panel green-lit a new way to measure success in multiple myeloma clinical trials, using a measurement called minimal residual disease.
- The ruling spurred changes in clinical trial designs for multiple myeloma, interest from other oncology fields and knock-on effects on technology development.
It’s been almost one year since the speed of multiple myeloma research got a big boost at the U.S. Food and Drug Administration (FDA).
Last April, a key agency committee ruled in favor of using a measurement called minimal residual disease (MRD) as an endpoint to support the accelerated approval of new treatments.
The FDA has not yet issued its final guidance, but MRD is already beginning to supplant older ways of assessing success in clinical trials, said C. Ola Landgren, M.D., Ph.D., from Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine.
Dr. Landgren, a professor in the Miller School’s Division of Myeloma, led an intensive research effort that propelled the new ruling supporting the use of MRD, a biomarker of disease that involves measuring minute numbers of cancer cells in the body. He spoke with us about key developments in the wake of the ruling, some of which will be discussed at the Miami Myeloma MRD Meeting 2025 on April 11.
Below are some of the key trends.
New Clinical Trial Designs to Speed Up Drug Approval
The FDA appears to be already encouraging changes in clinical trial design to incorporate MRD measurements, said Dr. Landgren.
Some biopharma companies have amended their protocols to include MRD as an endpoint in combination with progression-free survival, a clinical measurement that can take years to achieve, said Dr. Landgren. Whichever endpoint is met first will support the application for accelerated approval, a special regulatory pathway.
“I’ve talked to companies that have made these changes, and they all say that they have been able to amend their protocols with the FDA,” said Dr. Landgren. “I think that is fantastic, and I anticipate that it will lead to quicker access to new drugs for patients, and new treatment combinations.”
The trials are testing a host of new potential treatments for multiple myeloma, the second most common blood cancer. These treatments include cell therapies, agents called T cell engagers and antibody-drug conjugates, and small molecule compounds, said Dr. Landgren.
Adopting the MRD Endpoint
Dr. Landgren and his colleagues were pioneers, doing the painstaking work of collating and analyzing research on MRD in multiple myeloma to present before the FDA. The effort took more than a decade and involved the delicate process of convincing drug companies to share their data, in confidence, with the team.
Now, researchers in other fields of cancer research are asking Dr. Landgren how to follow the same path. In December, he and Sean Devlin, Ph.D., the project’s lead statistician, published a review outlining how their team did the work. And in February, Dr. Landgren spoke about his efforts at the Precision Medicine World Conference in Silicon Valley, where scientists studying both solid tumors and blood cancers came to him for advice.
“Many people are now thinking seriously about this,” said Dr. Landgren. “I really hope that other diseases could do it much faster, because when we did it, there was no known path. Now there is.”
Dr. Landgren is cautious about making predictions about which other fields will be next to adopt MRD as a similar endpoint.
Not all cancer types are a good fit. Multiple myeloma stands out because survival rates have soared as a host of new drugs have hit the market. The flip side of this success is that it now takes a long time and a lot of patients to show that a new treatment is superior to standard-of-care, using clinical measurements. MRD measurements can potentially cut years off of the timeline. Dr. Landgren cautions that other fields should similarly see high rates of success with current treatments before seeking the same path.
“I think it’s hard to say what the next disease will be,” said Dr. Landgren.
However, chronic lymphocytic leukemia and some types of lymphoma are good candidates, he said.
MRD is Shifting Thinking
MRD is typically measured using samples aspirated from bone marrow, often using flow cytometry.
Newer techniques rely increasingly on blood samples, which are easier to collect and are amenable to DNA analyses. The FDA ruling has ignited research on these and other new techniques to make MRD easier to measure and analyze, said Dr. Landgren.
Dr. Landgren and his colleagues have submitted data in support of the MRD endpoint to the European Medicines Agency and are awaiting a decision.
Researchers in multiple fields are studying ways to use MRD to help them make decisions about how to treat patients. Dr. Langren leads several clinical trials assessing the approach in multiple myeloma.
One question is whether some patients eligible for transplantation can forgo the expensive and sometimes risky procedure. In the ADVANCE trial, led by Dr. Landgren, multiple myeloma patients will only be offered transplantation if they show sustained MRD-positivity after initial rounds of treatment.
The trial may help Dr. Landgren and his colleagues fulfill their vision for the future of cancer treatment.
“The idea is that you can use MRD testing for decision-making to individualize treatment for each patient,” said Dr. Langren.
Once the state-of-the-art Kenneth C. Griffin Cancer Research Building, a cornerstone of Sylvester’s vision for advancing cancer discovery and care, opens later this year, clinical trials and collaboration will accelerate innovation and translational science. The Griffin Cancer Research Building will house many of Sylvester’s cancer researchers, cutting-edge technologies and clinical trials. This location will empower Dr. Landgren and his team to expand their work in multiple myeloma and related blood cancers, driving progress toward more precise, personalized treatment strategies.
Tags: cancer research, CAR T cells, Dr. C. Ola Landgren, FDA, minimal residual disease, multiple myeloma, Sylvester Comprehensive Cancer Center