ODAC Supports MRD Endpoint in Accelerated Approval for Multiple Myeloma

ODAC Supports MRD Endpoint in Accelerated Approval for Multiple Myeloma

The FDA’s Oncologic Drug Advisory Committee (ODAC) has unanimously voted in favor (12 yes, 0 no, 0 abstain) of using minimal residual disease (MRD) as an early endpoint for accelerated approval in multiple myeloma clinical trials.¹

“At 9 months and 12 months… the data are so strong at a patient level that I think [MRD as an] endpoint is reasonable to use,” committee member Chris Lieu, MD, Associate Professor of Medicine, Associate Director for Clinical Research, and Director, Gastrointestinal Medical Oncology, University of Colorado Cancer Center, said during the meeting.¹

Brian G.M. Durie, MD, Chief Scientific Officer, International Myeloma Foundation (IMF), submitted an independent new drug application to ODAC on behalf of the IMF comprising 10 years of collaborative research with the International Independent Team for Endpoint Approval in Multiple Myeloma (i2TEAMM) supporting the use of MRD as an endpoint for accelerated approval in the frontline settings of transplant-eligible, newly diagnosed multiple myeloma and non-transplant eligible, newly diagnosed multiple myeloma as well as for relapsed myeloma.

“On the heels of the FDA approvals for 2 chimeric antigen receptor (CAR) T-cell therapies in the relapsed setting of myeloma, I am thrilled to learn that today’s ODAC meeting will only continue to support the expansion of available treatment options for multiple myeloma patients. 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,” Yelak Biru, president and chief executive officer, IMF, also a 28-year myeloma survivor, said in a statement.²

READ MORE: Allogeneic CAR-T Yields Some Responses in Multiple Myeloma After Anti-BCMA Therapy

During the meeting, 2 separate meta-analyses were presented by experts from the University of Miami's Sylvester Comprehensive Cancer Center and i2TEAMM. The analyses demonstrated a strong association between MRD negativity and improved progression-free survival (PFS) and overall survival (OS) in patients with multiple myeloma in all treatment modalities, including CAR-T cells and T-cell engagers.

Jing Zhang, statistical reviewed for the FDA confirmed these associations but noted that trial-level associations were weaker in disease subpopulations for PFS and generally for OS. Also cautioning against the use of MRD and surrogate endpoints was Nicole Gormley, director, Division of Hematologic Malignancies II, Office of Oncologic Diseases, FDA.

“While I think durability is a good thing to know, I have this tremendous fear that this is going to mean every myeloma protocol has a marrow biopsy every 6 weeks on the patients forever and I just want to make sure that as sponsors think about designing their trials, they’re not thinking, all we need to do is more bone marrow and we’ll have this much statistical power to show the difference between 2 arms… so I just don’t want to see that happen. So, I just think we have to balance these things,” committee member Jorge J. Nieva, MD, Associate Professor of Clinical Medicine, Section Head, Solid Tumors, University of Southern California (USC), Norris Comprehensive Cancer Center Keck School of Medicine, said.¹

REFERENCES

1. April 12, 2024 Meeting of the Oncologic Drugs Advisory Committee Meeting Announcement. Website. FDA. April 12, 2024. https://www.fda.gov/advisory-committees/advisory-committee-calendar/april-12-2024-meeting-oncologic-drugs-advisory-committee-meeting-announcement-04122024
2. International Myeloma Foundation Celebrates ODAC Meeting Outcome on Minimal Residual Disease (MRD) Testing as an Early Endpoint for the Accelerated Approval of Myeloma Drugs in Clinical Trials: A Huge Win for the Global Myeloma Community. News release. IMF. April 12, 2024. https://www.globenewswire.com/news-release/2024/04/12/2862384/0/en/International-Myeloma-Foundation-Celebrates-ODAC-Meeting-Outcome-on-Minimal-Residual-Disease-MRD-Testing-as-an-Early-Endpoint-for-the-Accelerated-Approval-of-Myeloma-Drugs-in-Clini.html