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CLINICAL NEWS
• Azacitidine 75 mg/m2 on days 1-7 or days 1-5 and 8-9 plus placebo
Patients continued treatment until disease progression, lack of
benefit, or intolerance. The study’s primary endpoint was confirmed
as complete response (CR) within six cycles. Secondary endpoints
included progression-free survival (PFS) and overall survival (OS).
The median patient age was 69 years (range = 26-90 years).
After six cycles of treatment, 18 percent of patients in the pracinostat plus azacitidine group had achieved CR, compared with 33 percent in the azacitidine plus placebo group. A summary of response
rates is seen in TABLE 2.
TABLE 2. Summary of Response Rates in Patients Treated
with Azacitidine Plus Pracinostat or Placebo
Azacitidine

Complete remission (CR), within
180 days

Pracinostat
(n=51)

Placebo
(n=51)

18%

33%

20%

33%

Best response
CR
Partial remission (PR)

0%

0%

Marrow CR

28%

22%

Stable disease

26%

29%

Progressive disease

6%

6%

Hematologic improvement (HI)
Erythroid response

35%

55%

28%

45%

Platelet response

31%

53%

Neutrophil response

26%

39%

Clinical benefit rate (CR + PR + HI
+ molecular CR)

53%

63%

Cytogenetic response

42%

55%

Cytogenetic CR

24%

29%

Cytogenetic PR

18%

26%

PFS was similar, but slightly higher among patients treated with
pracinostat: 10.7 months compared with 9.2 months (hazard ratio
[HR]=0.93; p value was non-significant). OS, however, was slightly
higher among patients treated with azacitidine alone: 18.8 months
and 15.7 months (HR=1.21; p value was non-significant).
When added to azacitidine, pracinostat led to higher rates of
adverse events (AEs) than azacitidine alone, including:
• Grade 3 thrombocytopenia: 47% vs. 26%, respectively
• Grade 3 febrile neutropenia: 33% vs. 18%, respectively
• Grade 3 fatigue: 24% vs. 0%, respectively
These AEs were associated with higher rates of treatment discontinuation among pracinostat-treated patients, compared with those treated
with azacitidine alone: 26 percent and 10 percent, respectively.
“Pracinostat failed to improve the clinical effectiveness of
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2015 ASH Annual Meeting

azacitidine in this population of higher-risk MDS patients,” Dr.
Garcia-Manero and colleagues concluded. “This appears related to a
higher rate of early study discontinuation in the pracinostat group,
primarily due to adverse events.”
The researchers also conducted exploratory analyses in patients
who had received four or more treatment cycles to determine if
longer treatment duration affected safety and response. Patients
who tolerated treatment with pracinostat plus azacitidine for four or
more cycles appear to benefit compared with azacitidine alone, both
in terms of OS (HR=0.59) and duration of response (HR=0.48).
These results highlight the need to consider alternative doses and
schedules with pracinostat, the authors added.
Reference
Garcia-Manero G, Berdeja JG, Komrokji RS, et al. A Randomized, Placebo-Controlled,
Phase II Study of Pracinostat in Combination with Azacitidine (AZA) in Patients with
Previously Untreated Myelodysplastic Syndrome (MDS). Abstract #911. Presented at
the 2015 ASH Annual Meeting, December 7, 2015; Orlando, Florida.

Eltrombopag Increases
Platelet Counts in Patients
with Lower-Risk MDS and
Thrombocytopenia
For the 10 percent of patients with lower-risk myelodysplastic syndromes (MDS) who experience severe thrombocytopenia, there are few options for therapies to increase
platelet counts. Eltrombopag, an oral agonist of the thrombopoietin-receptor that has been approved by the U.S. FDA
for the treatment of idiopathic thrombocytopenic purpura
(ITP), has been suggested as a potential treatment for
these patients, but its efficacy has yet to be determined.
According to a recent study evaluating its safety and efficacy in inducing
platelet responses in patients with low and intermediate-1 risk (according
to the International Prognostic Score System [IPSS]) MDS with severe
thrombocytopenia, eltrombopag may lead to significant improvement in
platelet counts and fatigue (a common symptom of MDS).
Esther Natalie Oliva, MD, of the Azienda Ospedaliera Bianchi-Melacrino-Morelli in Reggio Calabria, Italy, and colleagues presented the interim results of the phase II, multicenter, prospective,
placebo-controlled, single-blind study at the ASH annual meeting
last month.
A total of 70 patients were randomized 2:1 to receive:
• Eltrombopag: starting dose of 50 mg once-daily, with 50 mg
increases every 2 weeks until a maximum 300 mg dose (n=46)
• Placebo (n=24)
Adult patients were eligible for study inclusion if they had platelet