Positive Vote by FDA ODAC Committee to use MRD as Earlier Myeloma Clinical Trial Endpoint

On April 12th, 2024, the Food and Drug Administration (FDA) ODAC Committee voted 12-0 in favor of using MRD as a new clinical trial endpoint for new multiple myeloma therapies that are on track for accelerated approval. An ODAC (Oncologic Drugs Advisory Committee) meeting is hosted by the FDA, and a committee of expert clinicians is assembled to review data on a particular subject that requires additional investigation. Once the committee votes, the FDA will consider that recommendation as they make a final decision. 

If the FDA adopts the recommendation, it will provide the ability for new drugs to receive earlier approvals instead of using traditional measurements like overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). This change is critical for patients. As myeloma treatments have improved and patients live longer, the old metrics require waiting over a decade for results from a single trial. If PFS is used, this can include up to two years to recruit enough patients into a trial and up to 8 years to show the statistical significance of the outcome.  

Minimal Residual Disease (MRD) testing is a more sensitive bone marrow biopsy test that can detect myeloma cells, even when the traditional monoclonal protein blood-based test can't. MRD testing has been available since 2009 and can be used to accurately measure how well a treatment worked as well as detect relapse earlier. 

Ola Landgren, MD, PhD of the Sylvester Cancer Center at the University of Miami, led the meeting to share over 15 years' worth of aggregated data from over a dozen studies in newly diagnosed multiple myeloma, called the EVIDENCE meta-analysis. Work was performed over the last decade in collaboration with the FDA, National Cancer Institute, and National Heart, Lung, and Blood Institute to evaluate MRD as a new potential clinical trial endpoint. The data presented was aggregated from 16 Phase II or Phase III randomized clinical trials.

Bruno Paiva, MD and Co-Director of the Flow Cytometry Platform of the University of Navarra, and Brian Durie, MD, and Chief Science Officer of the International Myeloma Foundation, shared additional data that confirmed these results. Dr. Paiva said:

“In myeloma, MRD negativity is the new complete remission.”

The accelerated approval of new therapies based on MRD negativity rates would be a significant shift in how clinical trials are constructed and run. Many myeloma therapies have been approved using the FDA's accelerated approval process. This pathway requires drugs to show an advantage over current treatments based on a biomarker or other endpoints that show clinical benefit, like overall response rate (ORR). ORR represents all patients who experience at least a 50% reduction in their disease. However, because 90-100% of patients meet that criteria in their first line of therapy, new markers must be developed to gauge impact.

Christopher Lieu, MD, University of Colorado Cancer Center and ODAC member, said:

“When you look at the data, especially the patient-level data, I think that's clear that it meets the criteria for accelerated approval. I think that MRD negativity is one of the most prognostic tests that we've seen in the disease.” 

Dr. Fanjana H. Advani, MD, Stanford University School of Medicine and ODAC member, stated: 

“I think this sets a precedence of actually moving the field forward, not only for the patients to get the drug earlier, but can we stop therapy based on MRD status? If the duration of MRD negativity is longer with better treatments, it kind of opens up a whole other way of even maybe treating patients where you don't have treat continuously, and instead you can get treatment gaps like you do in solid tumors.”

The FDA representatives, including Nicole Gormley, MD, and Bindu Kanapuru, MD, noted that the development of a new clinical trial endpoint needs to be validated with proven performance and standardized use of bone marrow collection and processing. The FDA members also stressed the importance of confirmatory trials to verify clinical benefit and the potential need to pull a drug from the market if accelerated approval was granted, but the confirmatory trials failed to verify benefit.

In addition to the confirmatory trial data, the HealthTree Foundation is uniquely positioned to invite patients to share their experience with side effects in the HealthTree Cure Hub. Studies with the aggregated data will help inform patients about both the impact of the new therapy and the associated side effects profile, so they can make educated decisions in partnership with their doctors. 

Michael Riotto, a myeloma patient and policy advocate, attended the meeting as an ODAC member. He stated: 

"I applaud the FDA ODAC for approving in a unanimous vote the use of MRD negativity as a surrogate end point in clinical trials. Equally important is that as a myeloma patient, I had a seat at the talbe to help make that decision." 

As a myeloma patient and patient advocate, I offer my voice of support for this landmark opinion. We will always have an unmet need as long as patients are relapsing after initial therapy and we have no cure. Over 15-35% of patients die after each myeloma therapy, so finding faster solutions for newly diagnosed myeloma patients is critical. 

If you want to continue learning about Minimal Residual Disease and how it is assessed in myeloma, you can check out the following resources:

• Watch our HealthTree University modules on MRD Testing.
• Register for our upcoming virtual workshop Miami Myeloma MRD Meeting on May 9th, 2024.
• Subscribe to our weekly newsletter for the latest MRD research and advancements in myeloma treatment.