News & Events

FDA’s Accelerated Approval Pathway: MRD as an Intermediate Endpoint in Multiple Myeloma Trials

On April 12, the FDA Oncologic Drugs Advisory Committee, or ODAC, met with leading multiple myeloma key opinion leaders (KOLs) and other stakeholders to discuss the topic of minimal residual disease, or MRD, as a clinical endpoint. Two groups, the Sylvester Comprehensive Cancer Center of Miami FL, led by Dr. Ola Landgren, and the i2TEAMM, led by Drs. Brian Durie (IMF) and Nikhil Munshi (DFCI), presented data from separate meta-analyses (meaning data from numerous previous studies that are combined to produce a summary study that is more likely to have statistically significant results) of previous clinical trials where MRD was measured at specific timepoints and then correlated to progression free survival (PFS) and overall survival (OS). These meta-analyses together involved 42 clinical trials and 21,006 patients in total.  Specifically, the question the ODAC discussed and voted on was “Does the data presented support the use of MRD as an intermediate clinical endpoint for accelerated drug approval in multiple myeloma?”

As a bit of background, the MMRF, in collaboration with Dr. Landgren and the FDA, has been supporting yearly meetings on this topic since 2014. There is a clear need for new therapies in myeloma, and with new immunotherapies currently lengthening the lives of patients and improving overall response rates (ORR), it has become more difficult to accumulate significant PFS data in trials in a reasonable timeframe, which is currently required for FDA approval; this can sometimes take up to 10 years, and many patients are unable to wait that long for new effective therapies to be approved. Using MRD measurement at a specific timepoint in a trial, 9 months and/or 12 months (+/- 3 months) after treatment is initiated, may provide assessment of sustained MRD, which is a hallmark of deep response to the clinical regimen.

After careful presentation of the data by both groups and an extended discussion with the FDA of the take-aways from the data, the ODAC panel voted 12-0 in favor of the use of MRD as an intermediate endpoint to support accelerated approval. What this means:

MRD testing may become more commonplace, but for now is mainly available only in major academic medical centers. For more information about this topic or anything else myeloma-related, please contact our patient navigators at 1-888-841-6673, Mon-Fri 9AM – 7PM ET, or by email at [email protected].