Emerging treatment options for myelofibrosis: focus on pacritinib

Figures & data

Table 1 Primary myelofibrosis: Dupriez, IPSS, and DIPSS scoring algorithms

Risk factors	Point value			Risk scorea (median survival, years)			Risk group
	Dupriez	IPSS	DIPSS	Dupriez	IPSS	DIPSS
Hgb <10 g/dL	1	1	2	0 (7.8)	0 (11.3)	0 (not reached)	Low
WBC <4 or >30×10^9/L	1	–	–	1 (2.2)	–	–	Intermediate
WBC >25×10^9/L	–	1	1
Age >65 years	–	1	1	–	1 (7.9)	1–2 (14.2)	Intermediate-1
Constitutional symptomsb	–	1	1	–	2 (2)	3–4 (4)	Intermediate-2
Peripheral blasts ≥1%	–	1	1	2 (1.1)	3–5 (2.3)	5–6 (1.5)	High

Notes:

a Risk score is determined by the sum of the point value assigned to each risk factor.

b Constitutional symptoms, defined as weight loss over 6 months, unexplained fever, and night sweats.

Abbreviations: IPSS, International Prognostic Scoring System; DIPSS, Dynamic International Prognostic Scoring System; Hgb, hemoglobin; WBC, white blood cell.

Table 2 Primary myelofibrosis: DIPSS-Plus scoring algorithm

Risk factors	Point value	Risk scorea (median survival, years)	Risk group
DIPSS intermediate-1	1	0 (15.4)	Low
DIPSS intermediate-2	2	1 (6.5)	Intermediate-1
DIPSS high risk	3	2–3 (2.9)	Intermediate-2
Platelet <100×10^9/L	1	4–6 (1.3)	High
RBC transfusion requirement	1	–	–
Unfavorable karyotypeb	1	–	–

Notes:

a Risk score is determined by the sum of the point value assigned to each risk factor.

b Unfavorable karyotype, defined as complex karyotype (3) chromosomal abnormalities, or 1–2 abnormalities that include +8, −5/5q−, −7/7q−, i(17q), 12p−, inv(3), or 11q23 rearrangement.

Abbreviations: DIPSS, Dynamic International Prognostic Scoring System; RBC, red blood cell.

Figure 1 JAK/STAT pathway and potential therapeutic targets.

Abbreviations: DNA, deoxyribonucleic acid; EPO, erythropoietin; IL, interleukin; JAK, Janus kinase; PI3K, phosphoinositide 3-kinase; P*, phosphorylation; MAPK, mitogen-activated protein kinase; mTOR, mammalian target of rapamycin; SOCS, suppressor of cytokine signaling; STAT, signal transducer and activator of transcription; TNF, tumor necrosis factor.

Figure 2 Molecular structure of pacritinib.

Table 3 Comparison of Phase III trials for pacritinib in myelofibrosis

	PERSIST-1	PERSIST-2
Title	Oral pacritinib vs best available therapy to treat myelofibrosis	Oral pacritinib vs best available therapy to treat myelofibrosis with thrombocytopenia
ClinicalTrials.gov identifier	NCT01773187	NCT02055781
Design	Randomized (2:1), open-label, multinational controlled trial	Randomized (2:1), open-label, multinational controlled trial
Participants	N=327; no platelet requirements	N=300 (estimated); platelets ≤100×10^9/L
Treatment arms	Pacritinib 400 mg once daily vs BAT excluding ruxolitinib	Pacritinib 400 mg once daily vs Pacritinib 200 mg twice daily vs BAT including ruxolitinib
Primary outcome	≥35% reduction in spleen volume from baseline to week 24 by MRI or CT	≥35% reduction in spleen volume from baseline to week 24 by MRI or CT
Secondary outcome	≥50% reduction in total score from baseline to week 24 on MPN-SAF TSS	≥50% reduction in total score from baseline to week 24 on MPN-SAF TSS

Abbreviations: BAT, best available therapy; MRI, magnetic resonance imaging; CT, computed tomography; MPN-SAF TSS, Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score.