On January 20, 2026, the U.S. Food and Drug Administration (FDA) released a draft guidance for industry regarding the use of measurable residual disease and complete response as primary endpoints in clinical trials evaluating drugs and biologics for the treatment of patients with multiple myeloma that would support their accelerated approval.
The draft guidance, entitled “Minimal Residual Disease and Complete Response in Multiple Myeloma: Use as Endpoints to Support Accelerated Approval,” provides specific recommendations for sponsors who are designing multiple myeloma clinical trials that are seeking to use minimal residual disease or complete response as an endpoint for an accelerated drug approval.
The draft guidance was issued in part as an acknowledgement of the fact that prior accelerated approvals using overall response rate as an endpoint have already surpassed high bars for response, requiring increasingly greater numbers of patients for future trials to demonstrate statistically significant improvements in overall response rates. Thus, other and more sensitive options for efficacy assessments were needed to support accelerated drug approvals.
In the guidance, minimal residual disease is defined as minimal residual disease negativity rate in the bone marrow that is determined using flow cytometry or next-generation sequencing methods for patients who have already achieved a complete response. The use of minimal residual disease as an acceptable endpoint for the accelerated approval of drugs or biologics for patients with multiple myeloma was first accepted by the Oncology Drug Advisory Committee in April 2024, following an FDA-performed pooled analysis of data analyzing the relationship between minimal residual disease and long-term outcomes. Additionally, the FDA previously released general recommendations to the industry for the use of minimal residual disease in the development of drug and biological products for the treatment of patients with hematologic malignancies.
The guidance defines complete response as patients who have achieved either a complete response or a stringent complete response.
As with other accelerated approvals, products granted an accelerated approval using minimal residual disease or complete response as endpoints will still be required to verify clinical benefit with standard endpoints of progression-free or overall survival.
Comments on the draft guidance can be submitted to the FDA.
