Literature Scan
New and noteworthy research from the
medical literature landscape
Adding Eltrombopag to Immunosuppression
Improves Hematologic Response in Patients
With Severe Aplastic Anemia
Acquired aplastic anemia (AA),
which results from immune-
mediated destruction of the bone
marrow, can often be treated with
immunosuppressive therapies.
Whether the efficacy of this
approach can be improved with the
use of growth factors to stimulate
the residual hematopoietic stem cells
characteristic of AA is not known.
Based on earlier research
showing that the thrombopoietin-
receptor agonist eltrombopag
improved hematologic response as
a single agent in patients with AA
refractory to immunosuppression,
Danielle M. Townsley, MD,
from the National Heart, Lung,
and Blood Institute, and co-
authors hypothesized that adding
eltrombopag to immunosuppressive
therapy as a firstline treatment
would increase rates of complete
TABLE.
response (CR) and improve long-
term outcomes in patients with AA.
According to the study’s
findings, published in the New
England Journal of Medicine,
this approach led to more than
one-third of patients achieving
a CR (primary endpoint) by 6
months. “Stimulating remaining
stem cells with a drug that mimics
the actions of a natural growth
substance for marrow stem cells
– while suppressing the immune
system – improves the likelihood,
quality, and speed of recovery
of these seriously ill patients,”
Dr. Townsley told ASH Clinical
News. “A much higher number of
patients responded to eltrombopag
combined with immunosuppressive
therapy, compared with prior
results in these patients using
immunosuppression alone.”
Hematologic Response to Immunosuppression Plus Eltrombopag
Rate at 3 Months Rate at 6 Months p Value
Overall response † 74 (80%)
(95% CI 72-89) 80 (87%)
(95% CI 80-94) <0.001
Partial response 46 (50%)
(95% CI 40-60) 44 (48%)
(95% CI 37-58) —
Complete response 28 (30%)
(95% CI 21-40) 36 (39%)
(95% CI 29-49) <0.001
Overall response 23 (77%)
(95% CI 61-93) 24 (80%)
(95% CI 65-95) —
Partial response 18 (60%)
(95% CI 41-79) 14 (47%)
(95% CI 28-66) —
Complete response 5 (17%)
(95% CI 3-31) 10 (33%)
(95% CI 15-31) 0.01
Overall response 24 (77%)
(95% CI 62-93) 27 (87%)
(95% CI 75-100) —
Partial response 16 (52%)
(95% CI 33-70) 19 (61%)
(95% CI 43-79) —
Complete response 8 (26%)
(95% CI 9-42) 8 (26%)
(95% CI 9-42) 0.06
Overall response 27 (87%)
(95% CI 75-100) 29 (94%)
(95% CI 84-103) —
Partial response 12 (39%)
(95% CI 21-57) 11 (35%)
(95% CI 18-53) —
Complete response 15 (48%)
(95% CI 30-67) 18 (58%)
(95% CI 40-76) <0.001
All Cohorts (n=92)
Cohort 1 (n=30)
Cohort 2 (n=31)
Cohort 3 (n=31)
The p value is for testing the comparison of the overall response rate to the overall response rate in a historic cohort (67 of 102 patients [66%]).
†
28
ASH Clinical News
The investigator-initiated,
non-randomized, historically-
controlled, phase I/II study enrolled
92 consecutive patients (≥2 years
old) with previously untreated
severe AA between June 2012
and November 2015. Patients
with Fanconi anemia, severe liver
impairment, or evidence of a clonal
myeloid disorder (per a cytogenetic
test performed within 12 weeks
prior to enrollment) were excluded.
All patients (median age = 32
years; range = 3-82 years) received
immunosuppression with horse
antithymocyte globulin (ATG; days
1-4) and cyclosporine daily for 6
months plus eltrombopag (150 mg
daily for patients ≥12 years old; 75 mg
daily for patients 6-11 years old;
and 2.5 mg/kg of body weight
per day in patients 2-5 years old).
Patients were split into three
cohorts based on the initiation and
duration of eltrombopag dosing:
• cohort 1: from day 14 to 6
months
• cohort 2: from day 14 to 3
months
• cohort 3: from day 1 to 6
months
The median baseline absolute
neutrophil count (ANC) was
310/mm 3 (range = 0-1,810/mm 3 ),
and the median baseline platelet
count was 9,000/mm 3 (range =
0-37,000/mm 3 ).
Investigators performed serial
bone marrow biopsies and measured
blood counts to assess hemat