FDA committee votes 12-0 for myeloma trial outcome measure
Agency will make final decision on use of MRD negativity for new treatments
A unanimous vote by a committee of the U.S. Food and Drug Administration (FDA) could lead to an early outcome measure — one known as minimal residual disease, or MRD negativity — being used for accelerated approval of treatments in clinical trials of multiple myeloma.
MRD refers to a very small number of cancer cells that remain in the body during or after treatment and that increase the risk of myeloma relapse.
While it’s still up to the FDA to make a final decision on the use of MRD negativity, researchers, including Carl Ola Landgren, MD, PhD, of the University of Miami’s Sylvester Comprehensive Cancer Center, are lauding the committee’s recommendation.
The 12-0 vote by the Oncologic Drugs Advisory Committee (ODAC) in favor of adopting the outcome measure “is a historic moment for the myeloma field,” Landgren said.
With current survival outcome measures, it can take up to eight years to show how well treatments work before they can be approved. The use of MRD negativity as a proxy of clinical response may allow approval of therapy candidates much sooner, supporters say.
An accelerated approval pathway allows the FDA to give conditional marketing authorization to medications based on biomarkers or other outcomes suggesting a likely benefit. Full approval is subsequently dependent on further evidence of the therapy’s efficacy using standard outcome measures.
IMF, other experts, voiced support at meeting for new outcome measure
The meeting by ODAC, an FDA advisory committee, was held earlier this month to discuss the use of MRD negativity in clinical trials — including when to measure it, which patients to include, and how to design future studies.
While the committee’s positive opinion will now be considered by the regulatory agency, it is non-binding. That means the FDA can agree, or not, in issuing its final decision.
During the meeting, the International Myeloma Foundation (IMF) voiced its support for using MRD testing in clinical trials, citing decade-long research by the International Independent Team for Endpoint Approval in Multiple Myeloma, known as i2TEAMM.
“I am thrilled to learn that [the] ODAC meeting will only continue to support the expansion of available treatment options for multiple myeloma patients,” Yelak Biru, IMF’s president and CEO, said in a foundation press release.
“It is the IMF’s vision to meet patients where they are in the stage of their disease and to realize a world where every myeloma patient can live life to the fullest, unburdened by this disease,” said Biru, who’s also a myeloma survivor.
I am thrilled to learn that [the] ODAC meeting will only continue to support the expansion of available treatment options for multiple myeloma patients.
In recent years, advances in treatment have translated into longer survival time for people with multiple myeloma, a cancer of the immune cells that produce antibodies. As patients live longer, there’s a need to monitor them for a longer time to prove if experimental treatments may further prolong survival or delay disease progression as compared with existing therapies.
Against this backdrop, there’s been growing interest in MRD negativity as a surrogate outcome measure that could predict treatment response in trials and allow for an earlier readout. MRD tests, including the clonoSEQ assay approved for use by the FDA in 2018, can detect tumor cells in the blood or bone marrow with a sensitivity down to 1 in 1 million cells.
Patients negative for minimal residual disease have a greater chance of surviving longer, and every fourth clinical trial already uses it as a readout.
In a presentation before the ODAC, Brian Durie, MD, IMF’s chief scientific officer working at the Cedars-Sinai Samuel Oschin Cancer Center, in Los Angeles, showed that MRD negativity could provide a readout for accelerated approval as early as 9-12 months.
MRD negativity, if approved, may hasten patient access to new therapies
The University of Miami’s Landgren, director of the Myeloma Research Institute at Sylvester, is one of the pioneers of studies evaluating MRD negativity as a potential early outcome measure in myeloma.
The proposed change “will give patients access to new therapies, many years sooner than with the current endpoints,” Landgren said in a university press release.
In another presentation at the ODAC meeting, Landgren shared the results of a meta-analysis study called EVIDENCE, for Evaluating Minimal Residual Disease as an Intermediate Clinical Endpoint for Multiple Myeloma. That study concluded that MRD negativity may be used to back accelerated approval of new treatments.
“We have worked relentlessly on this for 15 years, and we have had continuous FDA feedback throughout the process,” Landgren said, calling it “a very big undertaking.”
Landgren also believes that adopting this surrogate measure may have broader implications for other types of cancer.
It may “open the field for other diseases to move in the same direction, and it could give cancer patients access to therapy many years sooner, in a much broader context beyond myeloma,” Landgren said.
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