Notice2026-01068
Minimal Residual Disease and Complete Response in Multiple Myeloma: Use as Endpoints To Support Accelerated Approval; Draft Guidance for Industry; Availability
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Published
January 21, 2026
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA, Agency, or we) is announcing the availability of a draft guidance for industry entitled "Minimal Residual Disease and Complete Response in Multiple Myeloma: Use as Endpoints to Support Accelerated Approval." When finalized, this guidance will provide recommendations to sponsors about using minimal residual disease (MRD) and complete response (CR) in multiple myeloma as primary endpoints in trials evaluating drug and biological products intended to treat patients with multiple myeloma to support approval under accelerated approval.
Full Text
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<title>Federal Register, Volume 91 Issue 13 (Wednesday, January 21, 2026)</title>
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[Federal Register Volume 91, Number 13 (Wednesday, January 21, 2026)]
[Notices]
[Pages 2537-2539]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2026-01068]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2025-D-2616]
Minimal Residual Disease and Complete Response in Multiple
Myeloma: Use as Endpoints To Support Accelerated Approval; Draft
Guidance for Industry; Availability
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice of availability.
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SUMMARY: The Food and Drug Administration (FDA, Agency, or we) is
announcing the availability of a draft guidance for industry entitled
``Minimal Residual Disease and Complete Response in Multiple Myeloma:
Use as Endpoints to Support Accelerated Approval.'' When finalized,
this guidance will provide recommendations to sponsors about using
minimal residual disease (MRD) and complete response (CR) in multiple
myeloma as primary endpoints in trials evaluating drug and biological
products intended to treat patients with multiple myeloma to support
approval under accelerated approval.
DATES: Submit either electronic or written comments on the draft
guidance by March 23, 2026 to ensure that the Agency considers your
comment on this draft guidance before it begins work on the final
version of the guidance.
ADDRESSES: You may submit comments on any guidance at any time as
follows:
Electronic Submissions
Submit electronic comments in the following way:
<bullet> Federal eRulemaking Portal: <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to <a href="https://www.regulations.gov">https://www.regulations.gov</a>
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that identifies you in
the body of your comments, that information will be posted on <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
<bullet> If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').
Written/Paper Submissions
Submit written/paper submissions as follows:
<bullet> Mail/Hand Delivery/Courier (for written/paper
submissions): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
<bullet> For written/paper comments submitted to the Dockets
Management Staff, FDA will post your comment, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
Instructions: All submissions received must include the Docket No.
FDA-2025-D-2616 for ``Minimal Residual Disease and Complete Response in
Multiple Myeloma: Use as Endpoints to Support Accelerated Approval.''
Received comments will be placed in the docket and, except for those
[[Page 2538]]
submitted as ``Confidential Submissions,'' publicly viewable at <a href="https://www.regulations.gov">https://www.regulations.gov</a> or at the Dockets Management Staff between 9 a.m.
and 4 p.m., Monday through Friday, 240-402-7500.
<bullet> Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper submission. You
should submit two copies total. One copy will include the information
you claim to be confidential with a heading or cover note that states
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will
review this copy, including the claimed confidential information, in
its consideration of comments. The second copy, which will have the
claimed confidential information redacted/blacked out, will be
available for public viewing and posted on <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Submit both copies to the Dockets Management Staff. If you do not wish
your name and contact information to be made publicly available, you
can provide this information on the cover sheet and not in the body of
your comments and you must identify this information as
``confidential.'' Any information marked as ``confidential'' will not
be disclosed except in accordance with 21 CFR 10.20 and other
applicable disclosure law. For more information about FDA's posting of
comments to public dockets, see 80 FR 56469, September 18, 2015, or
access the information at: <a href="https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf">https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf</a>.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to <a href="https://www.regulations.gov">https://www.regulations.gov</a> and insert the docket number, found in brackets in
the heading of this document, into the ``Search'' box and follow the
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852, 240-402-7500.
You may submit comments on any guidance at any time (see 21 CFR
10.115(g)(5)).
Submit written requests for single copies of the draft guidance to
the Division of Drug Information, Center for Drug Evaluation and
Research, Food and Drug Administration, 10001 New Hampshire Ave.,
Hillandale Building, 4th Floor, Silver Spring, MD 20993-0002. Send one
self-addressed adhesive label to assist that office in processing your
requests. See the SUPPLEMENTARY INFORMATION section for electronic
access to the draft guidance document.
FOR FURTHER INFORMATION CONTACT: Bindu Kanapuru, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 22, Rm. 2102, Silver Spring, MD 20993, 240-402-
1279; Philip Kurs, Center for Biologics Evaluation and Research, Food
and Drug Administration, 240-402-7911; Center for Devices and
Radiological Health, Food and Drug Administration,
<a href="/cdn-cgi/l/email-protection#0b484f59434867626562686a674e7d626f6e65686e4b6d6f6a25636378256c647d"><span class="__cf_email__" data-cfemail="b6f5f2e4fef5dadfd8dfd5d7daf3c0dfd2d3d8d5d3f6d0d2d798dedec598d1d9c0">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a draft guidance for industry
entitled ``Minimal Residual Disease and Complete Response in Multiple
Myeloma: Use as Endpoints to Support Accelerated Approval.'' When
finalized, this guidance will provide recommendations to sponsors about
using MRD and CR in multiple myeloma as primary endpoints in trials
evaluating drug and biological products intended to treat patients with
multiple myeloma to support approval under accelerated approval. For
the purpose of this guidance, MRD endpoint refers to MRD negativity
rate as assessed in the bone marrow by either flow cytometry- or
sequencing-based methods in patients who have achieved a CR. The
definition of CR includes patients who achieved CR or stringent CR.
Multiple myeloma is a plasma cell malignancy and accounts for 18%
of all hematologic malignancies in the United States. In multiple
myeloma, accelerated approval based on an endpoint of overall response
rate (ORR, defined as a partial response or better) supported by
duration of response has expedited access to new therapies. However,
the overall response rates observed with new therapeutics have
surpassed 60-70% in the relapsed or refractory setting and 90% in the
newly diagnosed setting. With the improved outcomes observed in this
disease area, demonstrating statistically significant difference in
overall response rates may require infeasibly large clinical trials.
Additionally, more sensitive response assessments will allow for
continued expeditious drug development.
MRD, which is generally assessed in the bone marrow by either flow
cytometry- or sequencing-based methods, can further quantify the depth
of response to treatment beyond ORR or CR. MRD is a recognized
prognostic biomarker; patients who attain MRD-negativity have improved
long-term outcomes. The 2016 International Myeloma Working Group (IMWG)
incorporated standardized definitions of MRD-negative response resulted
in greater inclusion of these assessments in clinical trials. In this
treatment landscape, there has been interest in the use of MRD as a
primary endpoint for clinical trials intended to support regulatory
decision-making as opposed to an exploratory or a secondary endpoint.
At the April 12, 2024, Oncology Drug Advisory Committee meeting,
pooled analyses of clinical trial data submitted to the Agency was
presented to show the relationship between MRD and long-term outcomes
(i.e., Progression-Free Survival (PFS) and Overall Survival (OS)).
Members unanimously agreed that it is acceptable to use MRD as an
endpoint to support accelerated approval of drug or biological products
intended to treat multiple myeloma.
When finalized, this guidance will provide specific recommendations
for designing clinical trial using MRD as an endpoint for accelerated
approval. The recommendations include general drug development
considerations, trial design and statistical considerations, and assay
considerations for MRD evaluation.
The draft guidance also includes considerations when proposing CR
as an endpoint for accelerated approval as well as other regulatory
considerations. CR is also a recognized prognostic biomarker; patients
who attain CR have improved long-term outcomes. FDA conducted a pooled
analysis of clinical trial data, which demonstrated an association
between CR and long-term outcomes (i.e., PFS and OS). The 2016 IMWG
response criteria incorporate standardized definitions of CR and CR
rate, which have been assessed in numerous multiple myeloma trials,
often as a secondary endpoint with control of Type I error. Like MRD,
CR can be used as an endpoint to support accelerated approval in trials
evaluating drug and biological products intended to treat patients with
multiple myeloma.
This draft guidance is being issued consistent with FDA's good
guidance practices regulation (21 CFR 10.115). The draft guidance, when
finalized, will represent the current thinking of FDA on ``Minimal
Residual Disease and Complete Response in Multiple Myeloma: Use as
Endpoints to Support Accelerated Approval.'' It does not establish any
rights for any person and is not binding on FDA or the public. You can
use an alternative approach if it satisfies the requirements of the
applicable statutes and regulations.
As we develop final guidance on this topic, FDA will consider
comments on costs or cost savings the guidance may generate, relevant
for Executive Order 14192.
[[Page 2539]]
II. Paperwork Reduction Act of 1995
While this guidance contains no collection of information, it does
refer to previously approved FDA collections of information. The
previously approved collections of information are subject to review by
the Office of Management and Budget (OMB) under the Paperwork Reduction
Act of 1995 (PRA) (44 U.S.C. 3501-3521). The collections of information
in 21 CFR 201.56 and 201.57 have been approved under OMB control number
0910-0572; the collections of information in 21 CFR part 314 have been
approved under OMB control number 0910-0001; the collections of
information in 21 CFR part 601 have been approved under OMB control
number 0910-0338.
III. Electronic Access
Persons with access to the internet may obtain the draft guidance
at <a href="https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs">https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs</a>, <a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents">https://www.fda.gov/regulatory-information/search-fda-guidance-documents</a>, or <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Lowell M. Zeta,
Acting Deputy Commissioner for Policy, Legislation, and International
Affairs.
[FR Doc. 2026-01068 Filed 1-20-26; 8:45 am]
BILLING CODE 4164-01-P
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