1. Phase III PROUD-PV: Ropeginterferon α-2b Noninferior to Hydroxyurea in Polycythemia Vera
New Findings in Hematology: Independent Conference Coverage of ASH 2016*; December 3-6, 2016; San Diego, California
*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 activity is supported by educational grants from Amgen, Celgene Corporation, Incyte, Merck, and Seattle Genetics.

2. PROUD-PV: Background
Hydroxyurea is a recommended cytoreductive therapy for PV, but efficacy limited by resistance, intolerance[1]
IFN-based therapy has demonstrated hematologic response, decreased JAK2 V617F mutation allele burden in PV[2]
Ropeginterferon α-2b, novel monopegylated IFN α-2b
Longer elimination half-life allows administration every 14 days
Demonstrated hematologic and molecular response in 51 pts with PV in phase I/II dose escalation study (cORR 90%, CR 47%, PR 43%)[3]
Current phase III study compared safety, efficacy of ropeginterferon α-2b vs hydroxyurea in IFN-α–naive pts with PV[4]
cORR, cumulative ORR; IFN, interferon; PV, polycythemia vera.
1. Griesshammer M, et al. Ann Hematol. 2015; 94: Kiladjian JJ, et al. Blood. 2008;112: Gisslinger H, et al. Blood. 2015;126: Gisslinger H, et al. ASH Abstract 475.
Slide credit: clinicaloptions.com

3. PROUD-PV: Study Design
Multicenter, randomized, open-label, controlled phase III noninferiority study
Primary endpoints: CHR with or without spleen response at 12 mos, defined as normal hematocrit, leukocyte, and platelet counts, and normal spleen size (by central MRI) without phlebotomy in previous 3 mos
Secondary endpoints: RR over time, PMR, CMR, symptoms, QoL, AEs
Mo 12
PV pts with no prior IFN-α, autoimmune disease, or depression, plus either treatment naive and requiring cytoreduction, or HU experienced with no resistance, intolerance, or CR, and < 3 yrs of therapy
(N = 254)
Ropeginterferon α-2b*
(n = 127)
Hydroxyurea*
(n = 127)
*Response-driven dosing in both arms; up to 10 dose levels ( µg ropeginterferon α-2b every other wk or mg HU daily).
AE, adverse event; CHR, complete hematologic response; CMR, complete molecular response; HU, hydroxyurea; IFN, interferon; PMR, partial molecular response; QoL, quality of life; RR, response rate.
Slide credit: clinicaloptions.com
Gisslinger H, et al. ASH Abstract 475.

4. PROUD-PV: Baseline Characteristics
Ropeginterferon α-2b
(n = 127)
Hydroxyurea
White race, %
100
WHO 2008 PV diagnosis,* %
Female, %
53.5
52.8
Median age, yrs (range)
60 (30-85)
60 (21-81)
Median disease duration, mos (range)
1.9 (0-146)
3.6 (0-126)
Previous hydroxyurea, % 37
Mean hematocrit, % (SD)
49.5 (5.4)
49.8 (5.5)
Median spleen length, cm (range)
13.1 ( )
13.0 ( )
Normal or slightly enlarged spleen†, %
90.6
88.2
Spleen length < 17 cm/> 22 cm, %
9.4/2.4
11.8/3.9
Mean JAK2 V617F burden, % 42 43
PV, polycythemia vera; SD, standard deviation; WHO, World Health Organization.
*Confirmed by bone marrow biopsy. †Slightly enlarged defined as > 12 to 17 cm for women, > 13 to 17 cm for men.
Slide credit: clinicaloptions.com
Gisslinger H, et al. ASH Abstract 475.

5. PROUD-PV: Complete Hematologic Response
Mo 12 Response, n/N (%)
Ropeginterferon α-2b
Hydroxyurea
Treatment Difference, % (95% CI)
P Value
CHR
ITT PP
53/123 (43.1)
50/113 (44.3)
57/125 (45.6)
53/114 (46.5)
-2.5 (-14.9 to 9.9)
-2.2 (-15.2 to 10.7)
.0028*
.0036*
CHR with spleen normality†
26/122 (21.3)
34/123 (27.6)
-6.3 (-17.1 to 4.4)
.2233‡
*Noninferiority margin of 20%. †12 cm cutoff for women, 13 cm for men. ‡Noninferiority margin of 10.5%.
Ropeginterferon α-2b met criteria for noninferiority to hydroxyurea at Mo 12
No clinically relevant effect on spleen length observed in either arm
Most pts had near-normal spleen length at baseline
CHR, complete hematologic response; ITT, intent to treat; PP, per protocol population.
Slide credit: clinicaloptions.com
Gisslinger H, et al. ASH Abstract 475.

6. PROUD-PV: Specific AEs
Ropeginterferon α-2b
(n = 127)
Hydroxyurea
P Value
Endocrine disorders
3.1
0.8 NS
Psychiatric disorders
1.6
Cardiovascular disorders
Tissue disorders
AEs occurring in > 10% of pts in either arm
Anemia
6.3
24.4
< .01
Leukopenia
8.7
21.3
Thrombocytopenia
15.0
28.3
Nausea
2.4
11.8
Fatigue
12.6
13.4
Increased GGT
14.2
AE, adverse event; GGT, gamma-glutamyl transferase; NS, nonsignificant.
Slide credit: clinicaloptions.com
Gisslinger H, et al. ASH Abstract 475.

7. PROUD-PV: Overall Safety and Pt Disposition
AE, %
Ropeginterferon α-2b (n = 127)
Hydroxyurea (n = 127)
Any AE
81.9
87.4
Treatment-related AE
59.6
75.6
Grade 3 AE
16.5*
20.5†
*29 events in 21 pts. †45 events in 26 pts.
No grade 3 AEs occurred in > 10% of pts in either arm
D/c at Mo 12: ropeginterferon α-2b 16.5% vs hydroxyurea 12.6%
Dose reduction for AEs: ropeginterferon α-2b 25.2% vs hydroxyurea 51.2%
5 of 127 pts receiving hydroxyurea developed secondary related malignancies during study period (n = 2) or extended follow-up (n = 3)
No secondary related malignancies reported in pts receiving ropeginterferon α-2b
AE, adverse event; D/c, discontinuation.
Slide credit: clinicaloptions.com
Gisslinger H, et al. ASH Abstract 475.

8. PROUD-PV: Conclusions
Results demonstrate efficacy of ropeginterferon α-2b noninferior to that of hydroxyurea in pts with PV
CHR at Mo 12: 43.1% vs 45.6%
Treatment difference: -2.5% (95% CI: -14.9% to 9.9%; P = .0028)
Treatment-related AEs, dose reductions for AEs less frequent with ropeginterferon α-2b
Secondary related malignancies observed in 5 pts receiving hydroxyurea vs 0 pts receiving ropeginterferon α-2b during study period or extended follow-up
AEs, adverse events; CHR, complete hematologic response; PV, polycythemia vera.
Slide credit: clinicaloptions.com
Gisslinger H, et al. ASH Abstract 475.

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