CLINICAL NEWS
TABLE 1.
Changes in Platelet and Hemoglobin Levels in PERSIST-1 Patients with Thrombocytopenia
Mean platelet
Platelet <50,000/µL
Platelet <100,000/µL
n
Pacritinib
n
BAT
n
Pacritinib
n
BAT
Baseline
35
29,7000/µL
15
30,100/µL
68
56,100/µL
31
50,000/µL
Week 60
12
44,500/µL
0
Not available
30
68,900/µL
0
Not available
Baseline
35
9.8 g/dL
15
9.6 g/dL
72
10.0 g/dL
33
9.3 g/dL
Week 60
13
9.8 g/dL
0
Not available
31
10.5 g/dL
0
Not available
Mean hemoglobin
BAT = best available therapy
The median treatment duration with pacritinib was
15.1 months (range = 0.1-31.8 months). In the pacritinib
cohort, 60 percent of patients (n=133) discontinued
treatment – most often due to adverse events (AEs;
21%), while 96 percent of BAT-treated patients discontinued – most often due to physician decision (78%).
At week 60, 24 percent of evaluable pacritinib-treated
patients achieved SVR ≥35 percent. Most BAT-treated
patients (84%; n=90/107) crossed over to the pacritinib
cohort, and these patients “were able to achieve similar
responses to those receiving initial pacritinib therapy,”
Dr. Mesa and co-authors wrote. Nineteen percent of
evaluable patients who crossed over achieved an SVR
≥35 percent at week 36 post-crossover. The authors also
noted that, among these patients, the reduction in spleen
volume was maintained from week 24 to 36 (mean
percent change in spleen volume = −17% at week 24 and
−16% at week 36 after crossover).
The most common treatment-related AE with
initial pacritinib therapy was diarrhea (51% allgrade; 2.7% grade 3/4); the incidence was highest in
weeks one through eight of treatment, then dropped
to 12 percent in weeks eight through 16 (1.4% grade
3/4), 9 percent in weeks 16 through 24 (1.5% grade
3/4), and continued to decrease at subsequent time
points. A similar trend was seen among patients who
crossed over from BAT to pacritinib.
“There was no evidence of cumulative toxicities,” the
authors noted. Other AEs reported in the pacritinib and
BAT treatment groups included: anemia (29% and 22%),
thrombocytopenia (23% and 14%), neutropenia (5% and
2%), and peripheral neuropathy (1% and 4%).
Pacritinib in Patients with Thrombocytopenia
In the second study, Claire N. Harrison, DM, from the
Guys’ and St. Thomas’ National Health Services Foundation Trust in London, and authors examined longterm outcomes for the subset of PERSIST-1 patients
who had thrombocytopenia (platelets <100,000/μL or
<50,000/μL) at baseline.2
“Once a patient is diagnosed with myelofibrosis,
the incidence of disease-related thrombocytopenia
increases with time,” Dr. Harrison said during her
presentation of the results. “Patients with thrombocytopenia have significantly greater symptom
burden, distinct clinical characteristics, and shorter
overall survival rates. There is a significant unmet
need for patients with myelofibrosis who are unable
to tolerate or control their disease on other treatments due to low platelet counts.”
“One of the limitations of the only currently FDAapproved therapy, ruxolitinib, is that it is indicated in
patients with a platelet count above 50,000/µL,” Dr.
Mesa explained in an interview with ASH Clinical
News at last year’s ASCO Annual Meeting. “Many
patients with advanced disease have significant
thrombocytopenia, and that is a limiter for ruxolitinib
because the drug can cause thrombocytopenia.”
At baseline, approximately one-third of PERSIST-1 patients had thrombocytopenia: 72 in the
pacritinib-treated group and 34 in the BAT group.
Of the evaluable pacritinib-treated patients, 26
percent with baseline platelet <100,000/μL and 21
percent with <50,000/μL achieved SVR ≥35 percent
at 60-week follow-up. No BAT-treated patients with
baseline platelet <100,000/μL achieved this endpoint. For patients who crossed over to pacritinib,
31 percent of those with platelets <100,000/μL
and 31 percent with platelets <50,000/μL achieved
SVR >35 percent.
Pacritinib also appeared to offer sustained
symptom control. At week 24, 42 percent of patients
with platelets <100,000/μL and 32 percent of those
with platelets <50,000/μL experienced a ≥50 percent
reduction in TSS. At week 48 (the last assessment
per protocol), those numbers had increased to 61
percent and 78 percent, respectively. In addition,
mean platelet counts and hemoglobin increased
from baseline to week 60 among pacritinib-treated
patients (TABLE 1).
“It is encouraging to see that patients with baseline
thrombocytopenia who were treated with pacritinib
had stable mean platelet counts and hemoglobin levels
through the end of treatment,” Dr. Harrison added,
“and that some patients with very low platelets increased their platelet counts while receiving pacritinib
treatment.”
REFERENCES
1. Mesa RA, Egyed M, Szoke A, et al. Pacritinib (PAC) vs best available therapy (BAT) in
myelofibrosis (MF): 60 week follow-up of the phase III PERSIST-1 trial. Abstract #7065.
Presented at the 2016 American Society of Clinical Oncology Annual Meeting, Chicago,
IL, June 6, 2016.
2. Harrison CN, Egyed M, Szoke A, et al. Pacritinib (PAC) vs best available therapy (BAT) in
myelofibrosis (MF): Outcomes in patients (pts) with baseline (BL) thrombocytopenia.
Abstract #7011. Presented at the 2016 American Society of Clinical Oncology Annual
Meeting, Chicago, IL, June 6, 2016.
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