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overall survival rate at 2 years was 97
percent (95% CI 94-100).
Twelve patients underwent
allo-geneic hematopoietic cell
transplantation (alloHCT): Six had
not responded to eltrombopag, three
had a relapse (defined as declining
blood counts that warranted the
reintroduction of full-dose cyclospo-
rine), and three had clonal evolu-
tion (defined as the development
of the myelodysplastic syndromes
and acute myeloid leukemia from
AA). Two patients died following
alloHCT. When the researchers
censored the data for alloHCT, the
overall survival rate increased to 99
percent (95% CI 97-100).
Twenty-five of the 78 patients
(32%) who responded to eltrom-
bopag/immunosuppressive treat-
ment relapsed after 6 months. The
researchers amended the study
protocol to allow the continuation
of low-dose cyclosporine from 6
months to 2 years, and this reduced
the frequency of relapse: 14 percent
of patients (n=6/43) with a response
who continued therapy beyond 6
months relapsed, compared with 54
percent of patients (n=19/35) with a
response who stopped cyclosporine
at 6 months. Reinstituting cyclo-
sporine effectively reversed relapses
and increased blood counts in 13
of 25 patients, and the addition of
eltrombopag in combination with
cyclosporine reversed relapse in an
additional 10 patients.
Clonal evolution “was a concern”
for the researchers, but they noted
that the seven patients who experi-
enced chromosomal changes “were
within the range that would be
expected with immunosuppression
alone at 2 years,” the authors wrote.
The study is limited by its small
patient population, short duration
of follow-up, and non-randomized
design. Also, the authors were
not able to determine the exact
mechanism by which eltrom-
bopag acts in the context of bone
marrow failure. A large, random-
ized, placebo-controlled study is
underway in Europe to confirm
the results of the current trial. “The
median time to clonal evolution
with immunosuppressive therapy
is 4 to 6 years, which is longer than
the median follow-up of 2 years [in
this study],” the authors wrote.
Drs. Townsley and Winkler report
research funding from GlaxoSmith-
Kline and Novartis; Dr. Scheinberg
reports personal fees from Novartis.
Pembrolizumab Safe and Effective
in Heavily Pretreated Patients With
Classic Hodgkin Lymphoma
Though the standard of care for pa-
tients with relapsed/refractory classic
Hodgkin lymphoma (cHL) induces
high rates of response, duration of
response is estimated to be only 6
months. Failure of these therapies
(which include salvage chemo-
therapy, autologous hematopoietic
cell transplantation (AHCT), and
brentuximab vedotin [BV]) leave few
subsequent treatment options.
The U.S. Food and Drug
Administration approved
pembrolizumab in March 2017 for
adults and children with relapsed/
refractory cHL, based on results from
the multicenter, single-arm, phase II
KEYNOTE-087 trial. Patients treated
with the PD-1 inhibitor had an overall
response rate of 69 percent, with the
benefit persisting across subgroups
of patients with varying degrees of
prior therapies and transplant status,
according to an analysis published
in the Journal of Clinical Oncology
by Robert Chen, MD, from the City
of Hope National Medical Center in
Duarte, California, and colleagues.
The researchers evaluated the clinical
activity of pembrolizumab in 210
patients (median age = 35 years; range =
18-76 years) enrolled in KEYNOTE-087
who “represented the spectrum of
relapsed/refractory disease” and had
disease progression after:
• AHCT and subsequent BV
(cohort 1; n=69)
• salvage chemotherapy and BV
(cohort 2; n=81)
• AHCT, not including BV after
transplantation (cohort 3; n=60)
All patients had relapsed or refrac-
tory cHL after a median of four lines
of therapy (range = 1-1