On Tuesday, January 20, a draft guidance was released by the U.S. Food and Drug Administration (FDA) on how to use measurable/minimal residual disease (MRD) and complete response (CR) as endpoints in clinical trials for multiple myeloma drugs seeking accelerated approval.
The FDA noted that many earlier accelerated approvals relied on overall response rate (ORR), but response rates in multiple myeloma are now already very high. This makes it harder for new trials to show meaningful improvements without enrolling much larger numbers of patients. As a result, the FDA recognized the need for more sensitive measures of treatment effectiveness, such as MRD.
“Minimal Residual Disease and Complete Response in Multiple Myeloma: Use as Endpoints to Support Accelerated Approval,” explains how clinical trials can be designed to use these measures to help bring promising treatments to patients more quickly.
Based on the guidance, MRD is defined as the absence of detectable cancer cells in the bone marrow (or MRD negativity) among patients who have already achieved a complete response. Flow cytometry or next-generation sequencing (NGS) are used to measure MRD.
The definition of complete response includes both complete response and stringent complete response, which are established categories used to describe deep levels of disease control in multiple myeloma.
The use of MRD as an endpoint for accelerated approval in multiple myeloma was unanimously endorsed by the FDA’s Oncology Drug Advisory Committee (ODAC) in April 2024, following an FDA analysis showing a strong relationship between MRD status and long-term patient outcomes.
As it applies to accelerated approvals, drugs approved using MRD or complete response as primary endpoints must still confirm their clinical benefit in follow-up studies using standard outcomes such as progression-free survival or overall survival.
The FDA is accepting public comments on this draft guidance until March 23, 2026.
References:
Minimal Residual Disease and Complete Response in Multiple Myeloma: Use as Endpoints to Support Accelerated Approval — Draft Guidance for Industry, January 2026, U.S. Food and Drug Administration Guidance Document.
Minimal Residual Disease and Complete Response in Multiple Myeloma: Use as Endpoints to Support Accelerated Approval; Draft Guidance for Industry; Availability. Regulations.gov. ID FDA-2025-D-2616-0002.