FEATURE
Drawing First Blood
We invite two experts to debate controversial
topics in hematology and health care.
Are New Treatment Options for Beta-
Thalassemia Ready for Widespread Use?
Alexis Thompson, MD, MPH
Thomas Coates, 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 ashclinicalnews@
hematology.org.
ASHClinicalNews.org
Patients with transfusion-dependent beta-thalassemia, the most severe form of the disease, require
lifelong management with red blood cell (RBC) transfusions, presenting a substantial cost and burden to
patients. The only curative treatment for patients with transfusion-dependent beta-thalassemia is alloge-
neic hematopoietic cell transplantation (alloHCT), which also is associated with a variety of adverse events.
Also, many patients lack a suitable donor for the procedure.
Finding new treatment options for these patients is a high priority for the hematology community.
One of the most promising advances for patients with severe beta-thalassemia in recent years is the
use of gene therapy with autologous CD34-positive cells transduced with the beta globin–containing
lentiviral vector. Last year, 2018 American Society of Hematology (ASH) president Alexis A. Thompson,
MD, MPH, and colleagues published results of two companion phase I/II trials (HGB-204 and HGB-205)
in which gene therapy reduced or eliminated the need for long-term RBC transfusions in certain pa-
tients with transfusion-dependent beta-thalassemia. 1
Similar results from the phase III Northstar-2 and Northstar-3 studies shared at the 2018 ASH
Annual Meeting added to the excitement around using this type of gene therapy in patients with severe
beta-thalassemia. 2
Also at the 2018 ASH Annual Meeting, researchers presented findings from the phase III BELIEVE study
that evaluated luspatercept, a first-in-class recombinant fusion protein, in patients with transfusion-
dependent beta-thalassemia. Treatment with luspatercept alleviated patients’ transfusion burden, with
approximately 70% of participants achieving a clinically significant reduction in RBC transfusion require-
ments during any consecutive 12 weeks of treatment, the authors reported. 3
As the treatment options for transfusion-dependent beta-thalassemia continue to expand, ASH Clinical
News invited Dr. Thompson and Thomas Coates, MD, to discuss the status of these options and answer the
question, “In patients with transfusion-dependent thalassemia, should gene therapy be the first approach
or the last resort?”
Dr. Thompson is professor of pediatrics at Northwestern Medicine and Feinberg School of Medicine
in Chicago. Dr. Coates is professor of pediatrics at Keck School of Medicine at the University of Southern
California in Los Angeles.
Alexis Thompson, MD, MPH: In the very
near future, patients with beta-thalassemia
may have a variety of treatment options
that are either disease-modifying or poten-
tially curative, so we need to think about
which patients are the best candidates
for these therapies and what the intent of
therapy is.
Today, we have well-established
conventional therapies, including trans-
fusion and iron chelation (plus compre-
hensive care to manage complications),
that are sufficient for most patients. We
are thrilled to see adult patients with
beta-thalassemia living longer lives, but
these methods, while life-sustaining, are
not curative. Gene therapy represents a
promising option for older children and
young adults with beta-thalassemia, and
we are awaiting more information about
its safety in people older than 40 years.
Thomas Coates, MD: Gene therapy abso-
lutely is an exciting new option. Ulti-
mately, it probably will be the direction
that treatment will take, but right now, it
is just barely ready for prime time.
One of the most pressing issues is
that, in the U.S., few centers have exper-
tise in managing thalassemia. We both
know that if patients’ disease is managed
well with transfusion and their iron level
is controlled perfectly, they can expect to
live into their 60s. The caveat is that they
have to have a physician who under-
stands all the nuances of how to manage
the disease.
The ability to cure disease – especially
in a younger patient – and eliminate
decades of transfusions is a great opportu-
nity. The good and the bad news for gene
therapy, though, is that alloHCT methods
are also rapidly improving. So, there are
several competing options for patients
with severe beta-thalassemia.
Dr. Thompson: I agree; not every patient
is looking for curative therapy. Some
patients feel that their condition is being
managed effectively and that they have
made whatever lifestyle adjustments they
needed to achieve an acceptable qual-
ity of life. Given our improved ability
to provide safe blood and chelate iron
to control side effects, I can’t argue with
patients who want to make only minor
changes to therapy to maintain a certain
quality of life.
Others, like people with young chil-
dren, have great enthusiasm about gene
therapy. Research studies of gene therapy
have been conducted in adolescents and
young adults with beta-thalassemia, and
there are many reasons why this may be
the population where we see the greatest
long-term benefit.
For example, alloHCT with a sibling
donor is considered a standard of care for
transplant-eligible patients with beta-
thalassemia; many patients, however, lack
this type of suitable donor. Gene therapy
is quite appealing as an alternative, cura-
tive treatment.
Dr. Coates: Yes, if a patient has a matched
ASH Clinical News
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