CLINICAL NEWS
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FDA Issues Draft
Guidance on MRD
in Clinical Trials
To make drug development and evalu-
ation more efficient, the U.S. Food and
Drug Administration (FDA) issued draft
guidance on the use of minimal residual
disease (MRD) in the regulatory evalua-
tion of treatments for hematologic malig-
nancies. The agency’s guidance is based on
feedback from workshops with sponsors,
researchers, and regulators, as well as an
analysis of marketing applications that
showed inconsistent quality of MRD data.
“We’re focused on making the process
of generating pre-clinical and clinical
evidence required for making risk-based
regulatory decisions more modern, more
scientifically rigorous, and more efficient,”
FDA Commissioner Scott Gottlieb, MD,
said in a statement announcing the new
draft guidance. “[This document will]
provide drug developers greater clarity
and direction as they pursue the next
generation of therapies and treatments for
patients.”
The new guidance, which is open
for public comment, advised sponsors
to design trials that address two main
questions: “Is MRD as assessed (sample,
timing, threshold, etc.) a clinically valid
biomarker for the context of use (disease,
disease status, type of therapy, etc.)?” and
“Is the MRD assay used (or to be used)
in the clinical trial analytically valid for
the range of results that are important to
the trial?”
The guidance document also includes
disease-specific considerations for the
use of MRD in treatment evaluations. For
more information about the draft guid-
ance, visit www.fda.gov/Drugs/Guidance
ComplianceRegulatoryInformation.
Source: FDA news release, October 15, 2018.
CMS Finalizes
Physician Fee
Schedule for 2019
The Centers for Medicare and Medicaid
Services (CMS) released its final changes
to the Medicare Physician Fee Schedule
and the Quality Payment Program for
2019, which include substantial updates to
coverage of telehealth services. The final-
ized rule also revises proposed changes
to evaluation and management (E/M)
documentation requirements, based on
overwhelming negative responses to the
initial proposals.
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“Today’s rule finalizes dramatic
improvements for clinicians and patients
and reflects extensive input from the
medical community,” said CMS Adminis-
trator Seema Verma. “[It] offers immedi-
ate relief from onerous requirements that
contribute to burnout in the medical pro-
fession and detract from patient care.”
For example, the new rule elimi-
nates the requirement to document the
medical necessity of home visits, and
physicians will no longer be required to
re-record elements of history and physi-
cal exam when there is evidence that
the information has been reviewed and
updated.
CMS estimates that the new rule will
save clinicians $87 million in reduced
administrative costs in 2019 and $843
million over the next decade.
The agency also plans to continue its
controversial site-neutral billing policies,
which are designed to encourage fair
competition between medical services
provided by hospitals and those provided
by physicians. The agency also is making
changes to the Merit-based Incentive
Payment System, expanding the list of
eligible clinicians and adjusting which
quality measures it uses to rate partici-
pating physicians.
“Today’s rule
finalizes
dramatic
improvements
for clinicians
and patients
and reflects
extensive
input from
the medical
community.”
—SEEMA VERMA,
CMS Administrator
CMS will not implement any payment
changes until January 1, 2021, which will
allow the agency to collect stakeholder
input to further refine payment policies.
Source: CMS press release, November 1, 2018; American Society of
Hematology Practice Update, November 8, 2018.
FDA Approves
Elotuzumab-Based
Triplet Regimen for
Myeloma
The FDA approved the combination of
elotuzumab plus pomalidomide and
dexamethasone for the treatment of adult
patients with relapsed or refractory mul-
tiple myeloma (MM) who have received
at least two prior therapies, including
lenalidomide and a proteasome inhibitor.
The agency’s decision was based on
results from the randomized, phase II
ELOQUENT-3 trial, which compared the
elotuzumab combination with pomalido-
mide and dexamethasone alone. After a
median follow-up of 10.25 months (range
not reported), the triplet therapy doubled
both median progression-free survival
(PFS; 10.25 months vs. 4.67 months;
p=0.008) and overall response rate (53.3%
vs. 26.3%; p=0.003). This included a
higher rate of very good partial responses
or better in the elotuzumab group (20%
vs. 9%; p value not provided).
Serious adverse events (AEs) were
reported in 22 percent of patients treated
with the triplet therapy and in 15 percent
of patients in the control arm. AEs led to
treatment discontinuation of any drug in
5 percent of patients in the elotuzumab
arm and 1.8 percent in the pomalidomide-
dexamethasone arm.
Elotuzumab, an anti-SLAMF7
antibody, was previously approved in
combination with lenalidomide and dexa-
methasone for the treatment of patients
with MM who have received one to three
prior therapies.
Source: Bristol-Myers Squibb press release, November 6, 2018; FDA
approval letter, November 6, 2018.
FDA Expands
Brentuximab Vedotin’s
Indication
Brentuximab vedotin has been approved
in combination with chemotherapy for
the firstline treatment of adult patients
with certain peripheral T-cell lymphomas
(PTCLs).
The FDA granted this application pri-
ority review and breakthrough therapy
designation, and this is the first approval
for this indication.
The agency issued its decision through
an expedited review process for oncology
products, the Real-Time Oncology Re-
view (RTOR) program. “[This program]
allows the FDA to access key data prior to
the official submission of the application
allowing the review team to begin their
review earlier and communicate with the
sponsor prior to the application’s actual
submission,” explained Richard Pazdur,
MD, director of the FDA’s Oncology Cen-
ter of Excellence and acting director of
the Office of Hematology and Oncology
Products. “When the sponsor submits the
completed application, the review team
will already be familiar with the data and
be able to conduct a more efficient, timely
and thorough review. RTOR allowed the
FDA to approve this indication within
two weeks of the completed application’s
submission.”
“[The Real-Time
Oncology
Review program]
allows the
FDA to access
key data prior
to the official
submission of
the application.”
—RICHARD PAZDUR, MD
The decision was based on data from
a clinical trial of 452 patients with certain
PTCLs who received either brentuximab
vedotin plus chemotherapy or chemo-
therapy alone. Median PFS was signifi-
cantly longer in the brentuximab vedotin
group (48 months vs. 21 months [ranges
not provided]; p=0.01).
The most common AEs associated
with brentuximab vedotin included
peripheral neuropathy, nausea and
vomiting, diarrhea, leukopenia, fatigue,
mouth sores, constipation, hair loss, fever,
and anemia. The prescribing informa-
tion for brentuximab vedotin includes a
boxed warning about the risk of a fatal
or life-threatening progressive multifocal
leukoencephalopathy.
Brentuximab vedotin was previously
approved for the treatment of adult pa-
tients with previously untreated stage III
or IV classical Hodgkin lymphoma. ●
Source: FDA news release, November 16, 2018.
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