Drawing First Blood
We invite two experts to debate controversial
topics in hematology and health care.
Is MRD Testing Worthwhile in Myeloma?
Faith Davies, MD
Saad Z. Usmani, MD
Disclaimer:
The following positions were assigned
to the participants and do not
necessarily reflect ASH opinions, the
participants’ opinions, or what they
do in daily practice.
Agree? Disagree? We want
to hear from you! Send your
thoughts and opinions on
this controversial issue to
[email protected].
42
ASH Clinical News
With the clinically effective
treatment regimens now
available for myeloma, more
patients can achieve deep and
sustained responses. The ability
to measure minimal residual
disease (MRD) during and after
treatment has the potential
to help guide treatment
decisions and predict patients’
likelihood of relapse, but is MRD
monitoring ready to be used in
routine clinical practice?
ASH Clinical News invited
Faith Davies, MD, and
Saad Z. Usmani, MD, to debate
the question, “Is measuring
MRD worthwhile in myeloma?”
Dr. Davies, professor of
medicine and deputy director
of the Myeloma Institute at
the University of Arkansas
for Medical Sciences, will
argue on the “pro” side; Dr.
Usmani, chief of the Plasma
Cell Disorders Program and
director of clinical research
in hematologic malignancies
at Levine Cancer Institute/
Carolinas HealthCare System,
will argue on the “con” side.
Faith Davies, MD: Recently, a number
of new myeloma treatment options
have become available, with four new
agents receiving U.S. Food and Drug
Administration (FDA) approval since 2015:
the monoclonal antibodies daratumumab
and elotuzumab, the histone deacetylase
inhibitor panobinostat, and the proteasome
inhibitor ixazomib. This proliferation of
options has helped more patients with
myeloma achieve a complete response
(CR) and, along with these new treatment
options, the technology for detecting low
levels of disease has also improved to the
point that we are able to monitor patients’
MRD effectively.
Measuring MRD is informative
because patients who achieve an
MRD-negative state have a much better
prognosis. In a recent meta-analysis
of 21 studies that assessed MRD status
and progression-free survival (PFS) and
overall survival (OS) in patients with
newly diagnosed myeloma, the authors
found that patients who achieved MRD-
negative status had a PFS nearly twice
as long as patients who were MRD-
positive (54 vs. 26 months; p<0.001). 1
MRD-negative patients also had longer
OS (98 vs. 82 months; p<0.001), and the
association between MRD status and
survival persisted among patients who
achieved CR. There’s no doubt that it
is worthwhile for clinicians to measure
MRD as a signal of how well patients are
responding to treatment and to serve as a
guide as to their overall prognosis.
Saad Z. Usmani, MD: In principle, yes,
MRD testing is a fantastic idea. My
concern is that we haven’t fully vetted the
available platforms. Even among patients
who achieve CR, we don’t know the true
measure of underlying residual disease
because we still haven’t figured out the op-
timal technique for collecting these data.
The most common method for
detecting MRD in bone marrow (BM)
is flow cytometry. However, with this
method, we can only obtain a finite
number of samples, and the depth of
detectable MRD negativity is not optimal.
The estimated sensitivity is only 10 -4 ; other
methods allow us to detect myeloma cells
down to 10 -6 .
There is a lot of interest in developing
next-generation sequencing (NGS)
techniques to measure MRD, with the
hope that they will overcome some of
the limitations of flow cytometry and
polymerase chain reaction assays. This
technique isn’t ready to be used routinely
in clinical practice and the company
producing the only commercially
available NGS testing kit is trying to keep
pace with the growing sample volumes.
And these are just the samples being
analyzed from clinical trials, leaving
us to wonder what will happen when
that workload grows as physicians start
incorporating NGS techniques more
regularly in their practices.
These are the two methodologies of
greatest interest right now, but companies
are also actively developing other platforms.
July 2017