1. PERSIST-1: Reduction in Spleen Volume and Symptom Scores in MF With Pacritinib vs BAT
New Findings in Hematology: Independent Conference Coverage* of ASH 2015, December 5-8, 2015, Orlando, Florida
*CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs.
This program is supported by educational grants from Amgen, Celgene Corporation, Incyte, Merck, Seattle Genetics, and Takeda Oncology.

2. PERSIST-1: Background MF associated with
Few effective treatment options
Debilitating constitutional symptoms, splenomegaly, and progressive cytopenias in > 1/3 of pts[1]
Pacritinib: kinase inhibitor with specificity for JAK2, FLT3
Phase III PERSIST-1 trial of pacritinib in MF: ≥ 35% reduction in spleen size at Wk 24 vs BAT[2]
≥ 50% reduction in total symptom score at Wk 24 vs BAT
Current study examines outcomes from PERSIST-1 trial across subgroups[3]
BAT, best available therapy; MF, myelofibrosis.
1. Tefferi A, et al. Blood. 2013;122: Mesa RA, et al. ASCO Abstract LBA Vannucchi A, et al. ASH Abstract 58.
Slide credit: clinicaloptions.com

3. PERSIST-1: Study Design
Subgroup analysis of a randomized phase III trial[1]
Primary and secondary endpoints reached and reported previously[2]
Primary: ≥ 35% reduction in spleen volume by Wk 24
Secondary: ≥ 50% reduction in Total Symptom Score by Wk 24
Stratified by platelet count (≥ 100,000/µL vs 50, ,000/µL vs < 50,000/µL), risk category, region
Wk 24
Pacritinib mg QD PO (n = 220)
Pts with int/high-risk PMF, PET-MF, or PPV-MF;
palpable spleen ≥ 5 cm; no prior JAK2 inhibitors
(N = 327)
Crossover from BAT allowed after progression or after Wk 24 assessment
Best Available Therapy
Excluding ruxolitinib
(n = 107)
BAT, best available therapy; int, intermediate; MF, myelofibrosis; PET-MF, postessential thrombocythemia-myelofibrosis; PMF, primary myelofibrosis; PPV-MF, post–polycythemia vera myelofibrosis; TSS, total symptom score.
1. Vannucchi A, et al. ASH Abstract Mesa RA, et al. ASCO Abstract LBA7006.
Slide credit: clinicaloptions.com

4. PERSIST-1: Baseline Characteristics
Pacritinib
(n = 220)
BAT
(n = 107)
Median age, yrs (range)
67 (23-87)
65 (37-84)
Male, n (%)
125 (57)
60 (56)
Primary MF diagnosis, n (%)
144 (66)
59 (55)
Median spleen length, cm (range)
12 (4-33)
12 (4-30)
Median spleen volume, cm3 (range)
2006 ( )
2153 ( )
Median TSS, range
19 (< 1-48)
19 (2-56)
JAK2V617F positive, n (%)
154 (70)
92 (86)
WBC, n (%)
≤ 25 x 109/L
> 25 x 109/L
177 (80)
43 (20)
80 (75)
26 (24)
Hb, n (%)
< 10 g/dL
≥ 10 g/dL
84 (38)
136 (62)
47 (45)
RBC transfusion dependence, n (%)
35 (16)
15 (14)
Platelet count, n (%)
< 50,000/µL
≥ 50,000/µL to <100,000/µL
≥ 100,000/µL
37 (17)
148 (67)
16 (15)
18 (17)
73 (68)
BAT, best available therapy; Hb, hemoglobin; Int, intermediate; MF, myelofibrosis; RBC, red blood cell; TSS, total symptom score; WBC, white blood cell count.
Slide credit: clinicaloptions.com
Vannucchi A, et al. ASH Abstract 58.

5. PERSIST-1: Reduction of Spleen Volume ≥ 35% at Wk 24
Significantly greater percentage of pts in the pacritinib arm reached the primary endpoint 60
Pacritinib (n = 168)
Best available therapy (n = 85) 50 40 30 20 10
-10
Change From Baseline (%)
-20
-30
35% decrease
BAT, best available therapy; CT, computed tomography; ITT, intent to treat; MRI, magnetic resonance imaging; PAC, pacritinib.
-40
-50
Pts Reaching Primary Endpoint, %
Population
PAC
BAT
P Value
ITT
19.1
4.7
.0003
Evaluable*
25.0
5.9
.0001
-60
-70
-80
-90
-100
Patients
*Baseline + Wk 24 spleen assessment by MRI or CT.
Mesa RA, et al. ASCO Abstract LBA7006. Reprinted with permission.
Slide credit: clinicaloptions.com

6. PERSIST-1: Wk 24 Results
Splenomegaly: In the ITT population, 19.1% of pacritinib-treated pts had a ≥ 35% reduction in splenic volume vs 4.7% with BAT (P = .0003)
Similar reductions seen across all pt subgroups examined
≥ 35% reduction achieved independent of all risk factors examined except ECOG PS ≥ 2
Transfusion dependence: RBC transfusion independence was achieved by 25.7% of pacritinib-treated pts vs 0% with BAT (P = .04), with an increase from baseline in both Hb and platelet count
TSS: Overall, 24.5% of pacritinib-treated pts achieved ≥ 50% reduction in symptoms independent of baseline characteristics except bone pain score > 3
BAT, best available therapy; Hb, hemoglobin; Int, intermediate; ITT, intention to treat; MF, myelofibrosis; RBC, red blood cell; TSS, total symptom score.
Slide credit: clinicaloptions.com
Vannucchi A, et al. ASH Abstract 58.

7. PERSIST-1: Safety by DIPSS Risk Categories
Treatment-Related AEs, n (%)
Intermediate-1
Intermediate-2
High
Total Population
PAC
(n = 124)
BAT
(n = 49)
(n = 63)
(n = 43)
(n = 32)
(n = 14)
(n = 220)
(n = 106)
Hematologic
Anemia
Platelets ↓
Leukopenia
Neutropenia
30 (24)
22 (18)
4 (3)
2 (2)
11 (22)
6 (12)
19 (30)
18 (29)
5 (8)
6 (10)
6 (14)
2 (5)
1 (2)
11(34)
7 (22)
1 (3)
5 (36)
3 (21)
1 (7)
60 (27)
47 (21)
9 (4)
22 (21)
15 (14)
Non-hematologic
Diarrhea
Nausea
Vomiting
Epistaxis
66 (53)
35 (28)
21 (17)
7 (6)
4 (8)
2 (4)
3 (6)
41 (65)
13 (21)
9 (21)
3 (7)
4 (9)
22 (69)
10 (31)
8 (25)
3 (9)
2 (14)
129 (59)
65 (30)
43 (20)
15 (7)
14 (13)
7 (7)
6 (6)
10 (9)
AE, adverse event; BAT, best available therapy; GI, gastrointestinal; Int, intermediate; MF, myelofibrosis; DIPSS, Dynamic International Prognostic Scoring System
GI-related AEs usually resolved within 2 weeks; none were grade 4
Slide credit: clinicaloptions.com
Vannucchi A, et al. ASH Abstract 58.

8. PERSIST-1: Conclusions
Pacritinib-treated pts had consistent rates of SVR ≥ 35% and TSS reduction ≥ 50% regardless of baseline characteristics (including platelet count)
Pacritinib was superior to BAT for both endpoints across most pt subgroups
Investigators conclude that study results support use of pacritinib in the treatment of all intermediate- to high-risk MF patient subgroups analyzed
BAT, best available therapy; MF, myelofibrosis; SVR, spleen volume reduction; TSS, total symptom score.
Slide credit: clinicaloptions.com
Vannucchi A, et al. ASH Abstract 58.

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