FDA Draft Guidance Signals Shift Toward MRD, Complete Response as Accelerated Approval End Points in Multiple Myeloma

The FDA has released a draft guidance outlining how minimal residual disease (MRD) negativity and complete response (CR) may be used as clinical trial end points to support accelerated approval for therapies in multiple myeloma (MM), marking a significant evolution in regulatory thinking for this historically complex malignancy.¹ This guidance reflects growing confidence that deep responses measured at the molecular level can serve as meaningful predictors of long-term outcomes, potentially accelerating patient access to novel therapies.

MM has long been a drug development challenge, in part due to the complex nature of the disease and patient survival duration, which has made it difficult to use traditional end points such as overall survival (OS). The FDA draft guidance indicates a willingness to adopt measures of end points of drug efficacy earlier and more sensitively, as characterized by disease monitoring and treatment innovation.

Understanding MRD as a Regulatory End Point

MRD refers to a small number of cancer cells remaining after treatment that cannot be detected by routine diagnostic tests. In an individual with MM, the detection of MRD can be done by bone marrow-based assays, which can detect 1 tumor cell among 100,000 to 1 million normal cells.¹

The FDA’s draft guidance recognizes MRD negativity as a potential surrogate end point for clinical benefit, particularly when measured using validated, sensitive methodologies and prespecified timepoints. Importantly, the agency emphasizes that MRD should be evaluated as an independent end point, rather than solely in conjunction with traditional response categories such as complete response or very good partial response.¹

This approach follows from a developing awareness that depth of response, rather than severity of response, may be more strongly related to progression-free survival and outcomes in myeloma.

Accelerated Approval and Timely Patient Access

These accelerated approval pathways aim to make treatments for serious or life-threatening conditions available more quickly, based on surrogate end points that are reasonably likely to predict clinical benefit. In the past, myeloma drugs have used end points such as response rate or PFS, which require long follow-up periods.²

With the addition of MRD negativity and CR as acceptable end points for accelerated approval, the FDA seeks to expedite the process of drug development without compromising the quality of evidence. This shift has been well-received by both patient groups and scientists.

“We applaud the FDA’s acceptance of MRD as an end point for accelerated approval and their guidance for its application in multiple myeloma clinical trials,” Hearn Jay Cho, MD, PhD, chief medical officer of the Multiple Myeloma Research Foundation, said in a statement to Fierce. “This forward-thinking approach will undoubtedly bring novel agents to all myeloma patients sooner.”²

For oncology pharmacists, earlier approvals for oncology medications could equate to quicker integration of innovative therapies into treatment paradigms, yet also increase the educational need related to new mechanisms of action, monitoring requirements, and patient counseling considerations.

Key Elements of the FDA Draft Guidance

The FDA’s draft guidance outlines several critical considerations for sponsors seeking to use MRD negativity or CR as accelerated approval end points. Among these is the importance of clearly defining when MRD is assessed during a trial.

The agency states that the timepoint for assessing MRD negativity rate “should be prespecified and justified,” citing 9 months and 12 months after randomization as potential examples.¹ This requirement underscores the need for thoughtful trial design and alignment between clinical objectives and regulatory expectations.

Additionally, the FDA emphasizes that MRD assays must be analytically validated, standardized, and performed consistently across trial sites. Variability in sampling, assay sensitivity, and interpretation could undermine the reliability of MRD as a regulatory end point if not carefully controlled.¹

Expert Perspectives on Independent MRD Assessment

Experts in the field have highlighted the practical implications of treating MRD as an independent variable rather than a secondary confirmation of response depth. Ola Landgren, MD, PhD, from the Sylvester Comprehensive Cancer Center, who led one of the teams presenting data during the FDA’s Oncologic Drugs Advisory Committee meeting, described the guidance as both actionable and timely.²

The draft is “practical and to the point,” Landgren said in an email to Fierce. He further noted that “having bone marrow-based MRD testing as an independent variable (i.e., independent of CR/VGPR) seems like the way to go in the near-coming future.”²

This perspective reinforces the notion that MRD negativity may capture clinically meaningful differences between therapies that traditional response categories fail to distinguish.

Implications for Pharmacists and Clinical Practice

As MRD increasingly becomes a focus of regulatory decision-making, pharmacists will increasingly find themselves at the forefront of trial data interpretation and its application in real-world practice. Knowledge of MRD testing, its methodology, and its implications will become crucial for pharmacists working in treatment decision-making and patient education.

Not only may the increasing focus on MRD affect the duration of treatment, maintenance therapy, and treatment sequencing, in which areas pharmacists frequently contribute importantly, but also as new drugs receive accelerated approval on the basis of MRD results, the role of confirmatory postmarketing trials will continue to be important.³

REFERENCES

1. Minimal Residual Disease and Complete Response in Multiple Myeloma: Use as Endpoints to Support Accelerated Approval. FDA. Published January 2026. Accessed January 26, 2026. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/minimal-residual-disease-and-complete-response-multiple-myeloma-use-endpoints-support-accelerated

2. Liu A. FDA outlines draft policy on MRD, complete response for accelerated approvals in multiple myeloma. Fierce Biotech. Published January 21, 2026. Accessed January 26, 2026. https://www.fiercebiotech.com/biotech/fda-outlines-draft-policy-mrd-complete-response-accelerated-approvals-multiple-myeloma

3. Liu A. As FDA weighs another myeloma endpoint for accelerated approvals, experts say timely access is at stake. Fierce Pharma. Published April 9, 2024. Accessed January 26, 2026. https://www.fiercepharma.com/pharma/fda-weighs-another-multiple-myeloma-endpoint-accelerated-approval-timely-access-new-drugs