MRD Receives Support as a Biomarker for FDA Accelerated Approval in Myeloma Therapies

The 12 members of the US Food and Drug Administration (FDA) Oncology Advisory Drugs Committee (ODAC) unanimously voted in favor of the use of measurable residual disease (MRD)-negativity as an intermediate endpoint for US FDA Accelerated Approval in multiple myeloma (MM) clinical trials.

In addition to the voting question, the ODAC also discussed whether the data support the use of MRD in newly diagnosed and relapsed or refractory MM subgroups; the assessment timepoints of nine-month, 12-month, and any-time MRD-negative complete response; and the requirement for durability assessments.

Matt Maurer, DMSc, MS, of Mayo Clinic, said, “I echo everyone’s comments here about the strength of the work that’s been done over the last 10 years … to move endpoints forward. I think it shows that the accelerated approval process has been a big success in myeloma and I think MRD continues to move that forward. [MRD] clearly met the criteria of an intermediate clinical endpoint.”

Though several speakers did qualify some additional questions and uncertainties regarding the use of MRD as a marker in MM trials, none were overall opposed to the use of MRD in the context of the voting question.

“Because we live in the real-world, the evidence for a trial-level association is less robust … the endpoint will not perfectly capture clinical benefit in all scenarios, and may sometimes mislead us, but that’s why we are talking about accelerated approval,” Christopher Hourigan, MD, of Fralin Biomedical Research Institute at Virginia Tech, commented during the meeting. “There is harm to inaction, we are not currently curing people of MM and I’m not willing to make patients wait on principle for a theoretical perfect that may never come.”

The current chairperson of the ODAC, Ravi Madan, MD, of the National Cancer Institute, noted that, “I think the FDA showed that MRD does fall short of true surrogacy, but that’s a high bar and that wasn’t the question today. I think our clinical experts and the FDA both agree that MRD does meet the criteria for Accelerated Approval and that’s why I voted yes.”