ASH News Daily 2012 - Sunday, December 9, 2012 - (Page A-4)
Page A–4
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MYELOMA
Monoclonals and Their Plasma Cells: Characters
in Search of an Author
BY JOSE A. BUFILL, MD
L
ike an exclamation point in a
patient’s life story, the monoclonal
protein spike draws
our attention to a significant statement.
Attention must be paid. Is it
the first word of an epic tale or a
tasteless prank nature plays on an
unsuspecting victim? Monoclonal
proteins can be either or both, and
sorting through the various possible
narratives was the task of the
speakers at yesterday’s Education
Program session, “The Spectrum of
Plasma Cell Dyscrasias.” Morie A.
Gertz, MD, Mayo Clinic in Roches-
ter; Irene Ghobrial, MD, Dana-Farber
Cancer Institute in Boston; and
Giampaolo Merlini, MD, University
of Pavia, Italy, each approached the
difficult problem of the monoclonal
gammopathy from their own unique
perspectives and experience.
Finding a monoclonal protein is a
rare event. Prevalence rates in general
populations across continents
barely approach 5 percent. But they
are a common reason for referrals
to hematologists. And monoclonals
always test the skills of experienced
clinicians. Dr. Gertz narrated the stories
of several interesting patients
from his extensive library at the
Mayo Clinic to emphasize the difficult
diversity of plasma cell dyscrasias.
Monoclonals always reflect
a clonal disorder, but they don’t always
cause a clinical disorder. When
they do, they can range from subtle
to overwhelming. Hearing these
stories should help busy practicing
physicians pick out those subtle but
serious conditions that might mimic
monoclonal gammopathy of undetermined
significance (MGUS) at
first but soon take on a more aggressive
course.
Attendees listen to speakers at the Education Program session, “The Spectrum
of Plasma Cell Dyscrasias.”
Lymphomas
«« From Page A-1
treat patients with unfavorable molecular
profile? 2) What should we
do with an abnormal interim restaging
with fluorodeoxyglucose positron
emission tomography (FDGPET);
how is “abnormal” defined,
and should therapy be changed?
and 3) In the era of immuno-chemotherapy
(e.g., R-CHOP), should
DLBCL patients with primary refractory
or relapsed disease receive
novel therapy rather than autologous
stem cell transplantation in the
wake of the results of the Collaborative
Trial in Relapsed Aggressive
Lymphoma (CORAL) study?
The first question was addressed
by Laurie Sehn, MD, of the British
Columbia Cancer Agency in
Vancouver. Dr. Sehn reviewed pretreatment,
clinical, immunohistochemical,
and molecular prognostic
factors that help guide primary
therapy. She discussed how molec-
ular profiling may help us identify
potential targets for novel therapy
and whether it adds any benefit
to the IPI. Dr. Moskowitz took on
the second question himself. He reviewed
the use of FDG-PET in the
management of DLBCL, focusing
on its utility as a prognostic tool for
risk-adapted therapy in the primary
as well as the relapsed setting.
Finally, Christian Gisselbrecht, MD,
of the Hôpital Saint-Louis in Paris,
who was one of the lead investigators
in the CORAL study, concentrated
on the third question. Dr.
Gisselbrecht stated that “we may
be fighting a losing battle once a
patient relapses after primary therapy,”
as patients who have already
received optimal immuno-chemotherapy
possibly receive minimal
benefit with high-dose chemotherapy
and autologous stem cell transplantation.
Using the results of the
CORAL study as a platform, he described
treatment strategies for patients
with primary refractory and
Following the traditional threepart
classification scheme, Dr.
Merlini presented an overview
of MGUS in its various permutations:
those associated with IgM,
non-IgM, and light-chain phenotypes.
Each appears to write its
own unique story. Patients with
IgM and non-IgM MGUS differ in
that their respective plasma cell
clones develop either before or after
isotype switching, respectively.
As such, translocations in the immunoglobulin
heavy-chain region
– 14q32.24 – are seen in about half
of the non-IgM patients, but never
in those with IgM monoclonals. In
patients with IgG or IgA MGUS,
the risk for development of multiple
myeloma and related disorders
is well known. IgM MGUS can
be considered a distinct biological
entity whose phenotype leads to
Waldenström macroglobulinemia
(WM).
relapsed DLBCL. All of the presenters
emphasized that these important
questions will not be answered
without the willingness of investigators
and patients to participate
Dr. Ghobrial focused on IgM
monoclonals. Like its more common
cousin, multiple myeloma, WM often
develops from an MGUS clone and
smolders through an asymptomatic
stage before becoming symptomatic,
at times after many years. But the similarity
ends there. IgM MGUS seems
to be like a character in search of an
author. Like lymphoma, malignant
cells of WM can infiltrate and enlarge
lymph nodes and spleen. Like myeloma,
its monoclonal can wreak havoc.
An excess of clonal IgMs can cause
hemolysis, neuropathy, hyperviscosity,
skin rashes, Raynaud phenomenon,
and immune thrombocytopenic
purpura. They can interfere with laboratory
tests and induce coagulopathies.
In rare cases, light chains associated
with IgM monoclonals can cause
amyloidosis, infiltrating the heart and
kidneys.
Taken together, these three talks
illustrated the significant progress
attained in understanding the
pathogenesis and natural history of
these rare but fascinating diseases.
We can anticipate that – in the very
near future – the stories of most patients
with the plasma cell dyscrasias
will have a happy ending. If
you are interested in checking out
this session, it is taking place again
tomorrow at 7:00 a.m. in Room
A101, Level 1, building A.
Dr. Bufill indicated no relevant conflicts
of interest.
in clinical trials. I think “old blood
and guts” would have been proud.
Dr. Bishop indicated no relevant
conflicts of interest.
ASH NEWS DAILY
Sunday, December 9, 2012
Dr. Mary Cushman encourages the use of advocacy stickers for business
cards at the Grassroots Network Lunch.
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