CLINICAL NEWS
On Location 2014 ASH Annual Meeting
Continued from page 34
After a median follow-up of 24 months, the estimated probability of one-year overall survival was
86.6 percent (95% CI 70.8-94.2%), and the estimated probability of one-year progression-free survival
was 82.3 percent (95% CI 66.3–91.1%)
Five patients had relapsed by one year post-HSCT (three of whom subsequently died), totaling a cumulative incidence of relapse/progression of 12.5 percent (95% CI 4.5-24.8%). Incidence of transplantrelated mortality was 5.2 percent (95% CI 0.9-15.7%).
Notably, 11 of 38 evaluable patients (28.9%) were able to recover full hematologic function at 100
days post-transplant; this number increased to 24 of 32 evaluable patients (75%) at one year post-HSCT.
In terms of safety, 17 patients (42.5%) developed a total of 42 episodes of infection within one year of
receiving HCT, including nine “severe” infections.
TABLE.
Response Rates Before and After HSCT Transplant
Prior to transplant
(n = 40)
100 days post-HCT
(n = 39)
Complete remission
30 (75%)
36 (92.3%)
Partial remission
8 (20%)
“These results are an important advancement for patients and their
physicians seeking access to effective treatments,” Dr. Alvarnas commented. “Payers should also recognize that this treatment may now be
the best standard of care for these patients.”
This trial, conducted by the Blood and Marrow Transplant Clinical
Trials Network (BMT CTN) in collaboration with the AIDS Malignancy
Clinical Trials Consortium, also has implications for clinical research,
according to Richard Little, MD, head of hematologic, HIV and stem
cell therapeutics at the National Cancer Institute. “NCI sees a real need
for additional study of treatment options for HIV-infected patients with
malignancies,” said Dr. Little. “The results of this trial make us confident
that exclusion from autologous transplant studies on the basis of HIV
serostatus alone is no longer justified.”
An additional BMT CTN study is currently underway to demonstrate
the feasibility and safety of allogeneic blood stem cell transplants for
patients with chemotherapy-sensitive hematological malignancies and
HIV infection. ●
1 (2.6%)
Relapsed/progressive disease
2 (5%)
2 (5.1%)
Alvarnas J, Rademacher JL, Wang Y, et al. “Autologous Hematopoietic Stem Cell Transplantation (AHCT) in Patients with
Chemotherapy-Sensitive, Relapsed/Refractory (CSRR) Human Immunodeficiency Virus (HIV)-Associated Lymphoma (HAL):
Results from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN 0803)/AIDS Malignancy Consortium (AMC071) Trial.” Abstract #674. Presented at the ASH Annual Meeting, December 8, 2014.
New Compound Boosts Healthy
Red Blood Cell Production, Lowers
Anemia Burden in β-Thalassemia
ACE-536, a recombinant fusion protein containing
modified activin receptor type IIB and IgG Fc, has shown
promising results in the treatment of β-thalassemia,
reducing the need for transfusion and decreasing serum
ferritin levels, according to results from a preliminary
phase 2, dose-finding trial presented at the ASH Annual
Meeting.
β-Thalassemia is a blood disorder characterized by
reduced hemoglobin production, which may lead to iron
overload and organ failure. While patients with anemia
are typically treated with erythropoiesis-stimulating
agents (ESAs, which help the bone marrow produce red
blood cells), patients with β-thalassemia are unlikely to
respond well to conventional ESAs, said lead author, Antonio G. Piga, MD, in his discussion of the results.
The new compound ACE-536, though, uses a differ-
Investigators are
optimistic that ACE536 will reduce
or even eliminate
blood transfusions
for patients with
β-thalassemia.
36
ASH Clinical News
ent mechanism of action: it counteracts
the reduction in hemoglobin by binding
with ligands in the TGF-β super-family
and promoting late-stage erythroid differentiation.
To evaluate ACE-536’s ability to
stimulate effective erythropoiesis, Dr.
Piga and colleagues enrolled patients
with β-thalassemia into a phase 2,
multicenter, dose-finding trial. Patients
received subcutaneous injection of
ACE-536 once every three weeks, for up
to five doses, at sequentially increasing
dose levels (0.2, 0.4, 0.6, 0.8, or 1 mg/
kg). Preliminary data from the first 30
patients – seven transfusion-dependent
(TD) and 23 non-transfusion dependent
(NTD) patients – were presented.
Seventy-five percent of the 12 patients treated with
0.8-1.0 mg/kg ACE-536 met the study’s primary endpoints: three NTD patients experienced a ≥1.5 g/dL
hemoglobin increase and all six TD patients experienced
a ≥20 percent reduction in transfusion burden. ACE-536
also reduced transfusion burden by more than 60 percent
in all seven TD patients – across all dosing cohorts.
All five TD patients with iron overload at baseline
exhibited 12 to 60 percent reductions in serum ferritin
levels – a daily marker of iron status. Researchers also
observed ≥1 mg/g decreases in liver iron concentration in
eight of the 12 NTD patients with iron overload.
On the safety side, ACE-536 was generally well
tolerated, with no serious adverse events related to the
treatment. The most frequently reported adverse event