Minimal residual disease negative: A novel endpoint for accelerated approval; What providers should know.

On 12 April 2024, the US Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) voted (12-0) in support of minimal residual disease (MRD) as an accelerated approval endpoint for newly diagnosed multiple myeloma. MRD negativity in myeloma, defined by the IWMG, refers to bone marrow flow cytometry at specified time points after treatment which fail to detect malignant cells below some threshold (The ODAC discussed below < 10-5). The committee's rationale was based on data showing that MRD is prognostic- i.e. patients who achieve MRD negativity do better than those who do not- and that this endpoint is demonstrated months or years before progression free survival- the current criteria for FDA approval. While MRD promises to bring more drugs to patients sooner and earlier in the course of disease, we outline five open questions. Ultimately, providers and patients will have to consider whether they are willing to alter treatments based on MRD negativity or if further safety or efficacy data is desired.