2009-09-17
(WASHINGTON) – Myelodysplastic syndromes (MDS), a group of blood disorders that can
lead to acute myeloid leukemia (AML) in some patients, often cause severe
anemia (when the body lacks a sufficient number of functional red blood cells).
While certain treatments can help manage the symptoms of anemia, some studies
have suggested that they may lead to complications. A new study, however,
demonstrates that MDS patients with anemia may benefit from treatment with an
erythropoietin (EPO)-based regimen plus supportive care without added
complications as compared with those receiving supportive care alone. The study will appear
in the September 17 issue of Blood,
the official journal of the American Society of Hematology.
The phase III prospective, randomized
trial, conducted by research teams of the Eastern Cooperative Oncology Group,
was designed to evaluate the efficacy and safety of EPO with or without myeloid
growth factor treatment (G-CSF, or granulocyte colony-stimulating factor) and
supportive care (SC) with red blood cell transfusions for patients with early-stage
MDS (n=53), in comparison to supportive care alone (n=57).
For the study, the researchers followed
MDS treatment and dosing guidelines recommended by the National Comprehensive
Cancer Network, which include managing anemia with erythropoiesis-stimulating
agents (ESAs) such as EPO. EPO is a drug that
imitates the action of the hormone erythropoietin, which stimulates the body to
produce more red blood cells. Generally, therapy with
G-CSF interacts with EPO treatment synergistically to improve erythroid (red
blood cell) responses, especially in MDS patients that do not respond to EPO
alone.
“EPO is a recommended treatment for MDS,
but the combination with G-CSF and supportive care required comparative studies
in this patient population,” according to lead study author Peter Greenberg,
MD, Professor of Medicine, Stanford University Cancer Center. “Our goal was to
manage anemia while not increasing the risk of transformation to leukemia, and
we undertook this study to understand if this combination might be successfully
utilized in these patients.”
The results of the study proved
successful for this group of patients with lower-risk MDS and anemia. After the
first course of therapy, 36 percent of patients in the EPO arm responded to treatment,
compared with only 9.6 percent in the SC alone arm. After subsequent courses,
47 percent responded in the EPO arm. Researchers then followed both patient
groups for a median of 5.8 years to determine their long-term response to
treatment. Responders to EPO experienced increased survival in comparison to
the non-responders (5.5 vs. 2.3 years) and significantly improved physical,
emotional, and functional well-being, reduced fatigue, and improved overall
quality of life. The research team otherwise found no statistically significant
differences in overall survival of
patients between the EPO and SC arms (3.1 vs. 2.6 years) or the incidence of
transformation to AML (7.5 vs. 10.5 percent of patients, respectively),
suggesting long-term safety of the EPO treatment regimen.
The study results also indicated that
the combination of EPO plus G-CSF was beneficial for patients who either did
not respond initially to EPO or who experienced a delayed response. Furthermore, higher doses of EPO seemed to
prove valuable for a proportion of patients who initially failed to respond.
Importantly, the outcomes suggested long-term tolerance to the treatment
combination, with a low overall incidence of adverse events. Specifically, the
researchers found no significant treatment-related increase in incidence of
either cardiovascular or thrombotic (clotting) events or transformation to AML
in the patients who received EPO alone or with G-CSF, as compared with those in
the SC arm.
Recently, the FDA has issued alerts regarding
the use of ESAs, noting increased mortality, possible tumor promotion, and
thromboembolic events that have been observed in some studies of non-MDS
patients receiving ESAs. However, other
studies of patients with solid tumors receiving chemotherapy did not
demonstrate an adverse effect of ESAs on survival.
“We believe the data suggest that the
negative effects of cytokines, like ESAs, demonstrated in some studies of other
diseases may relate to biologic and clinical features or the specific treatments
associated with the differing disorders studied,” said Dr. Greenberg. “Findings
from this study demonstrate the relative safety and efficacy of EPO plus G-CSF
for treating anemic lower-risk MDS patients and may be considered as part of
future treatment recommendations for the use of this class of therapies.”
Additional
links:
Reporters
who wish to receive a copy of the study or arrange an interview with Dr.
Greenberg may contact Patrick Irelan
at 202-776-0544 or pirelan@hematology.org.
The
American Society of Hematology (www.hematology.org)
is the world’s largest professional society concerned with the causes and
treatment of blood disorders. Its mission is to further the understanding,
diagnosis, treatment, and prevention of disorders affecting blood, bone marrow,
and the immunologic, hemostatic, and vascular systems, by promoting research,
clinical care, education, training, and advocacy in hematology. ASH provides Blood: The Vital Connection (www.bloodthevitalconnection.org), a
credible online resource addressing bleeding and clotting disorders, anemia,
and cancer. It features hematologist-approved information about these common
blood conditions including risk factors, preventive measures, and treatment
options.
Blood, the official journal of ASH, is the most cited
peer-reviewed publication in the field. Blood
is issued to Society members and other subscribers weekly and is available in
print and online at www.bloodjournal.org.
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