Dr Landgren on the Rationale for Utilizing MRD as a Clinical Trial End Point in Myeloma

C. Ola Landgren, MD, PhD, professor, medicine, Department of Medicine, chief, Division of Myeloma, Department of Medicine, co-leader, Translational and Clinical Oncology Program, Paul J. DiMare Endowed Chair in Immunotherapy, director, Sylvester Myeloma Institute, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, University of Miami Health System, discusses the rationale for utilizing minimal residual disease (MRD) as an end point in clinical trials evaluating treatments for patients with multiple myeloma.

Notably, in April 2024, the FDA’s Oncologic Drugs Advisory Committee voted that available data support the use of MRD as an end point for accelerated approval of new treatments for patients with multiple myeloma.

As therapies for patients with multiple myeloma have improved, despite not being curative, they have improved overall response rates for this patient population, Landgren begins. This highlights a challenge in designing randomized clinical trials evaluating novel agents or regimens; as the control treatments increasingly generate higher response rates, it becomes difficult to develop new drugs that could demonstrate a clear advantage in ORR, he explains.

In response to this challenge, Landgren and colleagues initiated an evidence meta-analysis project in 2009 that included reaching out to pharmaceutical companies with datasets that included MRD testing, which were relatively rare at the time. Concurrently, within the National Cancer Institute, investigators worked on developing cutting-edge MRD assays, he expands. By approximately 2014, investigators invited external collaborators, including academic groups and patient organizations, to join the effort, Landgren adds. A meeting was organized with the FDA to share these ideas and data. This collaboration aimed to refine approaches and expand the scope of research by utilizing MRD, Landgren expands.

In addition, Landgren says he filed an investigational new drug application for MRD as an end point to support accelerated approval of treatments for patients with multiple myeloma, using the same mechanism that pharmaceutical companies use when seeking FDA approval for new drugs. This effort aimed to help streamline the approval process and bring effective treatments to patients in a timely manner, Landgren concludes.