Pacritinib versus best available therapy for the treatment of
myelofibrosis irrespective of baseline cytopenias (PERSIST-1):
an international, randomised, phase 3 trial

J 2017

Pacritinib versus best available therapy for the treatment of myelofibrosis irrespective of baseline cytopenias (PERSIST-1): an international, randomised, phase 3 trial

MESA, R.A., A.M. VANNUCCHI, A. MEAD, M. EGYED, A. SZOKE et. al.

Basic information

Original name

Pacritinib versus best available therapy for the treatment of myelofibrosis irrespective of baseline cytopenias (PERSIST-1): an international, randomised, phase 3 trial

Authors

Edition

The Lancet. Haematology, England, ELSEVIER SCI LTD, 2017, 2352-3026

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30205 Hematology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 10.698

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1016/S2352-3026(17)30027-3

UT WoS

000405451800011

Keywords in English

Pacritinib

Abstract

V originále

Background Available therapies for myelofibrosis can exacerbate cytopenias and are not indicated for patients with severe thrombocytopenia. Pacritinib, which inhibits both JAK2 and FLT3, induced spleen responses with limited myelosuppression in phase 1/2 trials. We aimed to assess the efficacy and safety of pacritinib versus best available therapy in patients with myelofibrosis irrespective of baseline cytopenias. Methods This international, multicentre, randomised, phase 3 trial (PERSIST-1) was done at 67 sites in 12 countries. Patients with higher-risk myelofibrosis (with no exclusions for baseline anaemia or thrombocytopenia) were randomly assigned (2: 1) to receive oral pacritinib 400 mg once daily or best available therapy (BAT) excluding JAK2 inhibitors until disease progression or unacceptable toxicity. Randomisation was stratified by risk category, platelet count, and region. Treatment assignments were known to investigators, site personnel, patients, clinical monitors, and pharmacovigilance personnel. The primary endpoint was spleen volume reduction (SVR) of 35% or more from baseline to week 24 in the intention-to-treat population as assessed by blinded, centrally reviewed MRI or CT. We did safety analyses in all randomised patients who received either treatment. Here we present the final data. This trial is registered with ClinicalTrials. gov, number NCT01773187. Findings Between Jan 8, 2013, and Aug 1, 2014, 327 patients were randomly assigned to pacritinib (n = 220) or BAT (n = 107). Median follow-up was 23.2 months (IQR 14.8-28.7). At week 24, the primary endpoint of SVR of 35% or more was achieved by 42 (19%) patients in the pacritinib group versus five (5%) patients in the BAT group (p = 0.0003). 90 patients in the BAT group crossed over to receive pacritinib at a median of 6.3 months (IQR 5.8-6.7). The most common grade 3-4 adverse events through week 24 were anaemia (n = 37 [17%]), thrombocytopenia (n = 26 [12%]), and diarrhoea (n = 11 [5%]) in the pacritinib group, and anaemia (n = 16 [15%]), thrombocytopenia (n = 12 [11%]), dyspnoea (n = 3 [3%]), and hypotension (n = 3 [3%]) in the BAT group. The most common serious adverse events that occurred through week 24 were anaemia (10 [5%]), cardiac failure (5 [2%]), pyrexia (4 [2%]), and pneumonia (4 [2%]) with pacritinib, and anaemia (5 [5%]), sepsis (2 [2%]), and dyspnoea (2 [2%]) with BAT. Deaths due to adverse events were observed in 27 (12%) patients in the pacritinib group and 14 (13%) patients in the BAT group throughout the duration of the study. Interpretation Pacritinib therapy was well tolerated and induced significant and sustained SVR and symptom reduction, even in patients with severe baseline cytopenias. Pacritinib could be a treatment option for patients with myelofibrosis, including those with baseline cytopenias for whom options are particularly limited.

Citovat

MESA, R.A., A.M. VANNUCCHI, A. MEAD, M. EGYED, A. SZOKE, A. SUVOROV, J. JAKUCS, A. PERKINS, R. PRASAD, Jiří MAYER, J. DEMETER, P. GANLY, J.W. SINGER, H.F. ZHOU, JP DEAN, P.A. te BOEKHORST, J. NANGALIA, J.J. KILADJIAN and C.N. HARRISON. Pacritinib versus best available therapy for the treatment of myelofibrosis irrespective of baseline cytopenias (PERSIST-1): an international, randomised, phase 3 trial. The Lancet. Haematology. England: ELSEVIER SCI LTD, 2017, vol. 4, No 5, p. "E225"-"E236", 12 pp. ISSN 2352-3026. Available from: https://dx.doi.org/10.1016/S2352-3026(17)30027-3.

@article{1398954,
   author = {Mesa, R.A. and Vannucchi, A.M. and Mead, A. and Egyed, M. and Szoke, A. and Suvorov, A. and Jakucs, J. and Perkins, A. and Prasad, R. and Mayer, Jiří and Demeter, J. and Ganly, P. and Singer, J.W. and Zhou, H.F. and Dean, JP and Boekhorst, P.A. te and Nangalia, J. and Kiladjian, J.J. and Harrison, C.N.},
   article_location = {England},
   article_number = {5},
   doi = {http://dx.doi.org/10.1016/S2352-3026(17)30027-3},
   keywords = {Pacritinib},
   language = {eng},
   issn = {2352-3026},
   journal = {The Lancet. Haematology},
   title = {Pacritinib versus best available therapy for the treatment of myelofibrosis irrespective of baseline cytopenias (PERSIST-1): an international, randomised, phase 3 trial},
   url = {http://dx.doi.org/10.1016/S2352-3026(17)30027-3},
   volume = {4},
   year = {2017}
}

TY  - JOUR
ID  - 1398954
AU  - Mesa, R.A. - Vannucchi, A.M. - Mead, A. - Egyed, M. - Szoke, A. - Suvorov, A. - Jakucs, J. - Perkins, A. - Prasad, R. - Mayer, Jiří - Demeter, J. - Ganly, P. - Singer, J.W. - Zhou, H.F. - Dean, JP - Boekhorst, P.A. te - Nangalia, J. - Kiladjian, J.J. - Harrison, C.N.
PY  - 2017
TI  - Pacritinib versus best available therapy for the treatment of myelofibrosis irrespective of baseline cytopenias (PERSIST-1): an international, randomised, phase 3 trial
JF  - The Lancet. Haematology
VL  - 4
IS  - 5
SP  - "E225"-"E236"
EP  - "E225"-"E236"
PB  - ELSEVIER SCI LTD
SN  - 23523026
KW  - Pacritinib
UR  - http://dx.doi.org/10.1016/S2352-3026(17)30027-3
L2  - http://dx.doi.org/10.1016/S2352-3026(17)30027-3
N2  - Background Available therapies for myelofibrosis can exacerbate cytopenias and are not indicated for patients with severe thrombocytopenia. Pacritinib, which inhibits both JAK2 and FLT3, induced spleen responses with limited myelosuppression in phase 1/2 trials. We aimed to assess the efficacy and safety of pacritinib versus best available therapy in patients with myelofibrosis irrespective of baseline cytopenias. Methods This international, multicentre, randomised, phase 3 trial (PERSIST-1) was done at 67 sites in 12 countries. Patients with higher-risk myelofibrosis (with no exclusions for baseline anaemia or thrombocytopenia) were randomly assigned (2: 1) to receive oral pacritinib 400 mg once daily or best available therapy (BAT) excluding JAK2 inhibitors until disease progression or unacceptable toxicity. Randomisation was stratified by risk category, platelet count, and region. Treatment assignments were known to investigators, site personnel, patients, clinical monitors, and pharmacovigilance personnel. The primary endpoint was spleen volume reduction (SVR) of 35% or more from baseline to week 24 in the intention-to-treat population as assessed by blinded, centrally reviewed MRI or CT. We did safety analyses in all randomised patients who received either treatment. Here we present the final data. This trial is registered with ClinicalTrials. gov, number NCT01773187. Findings Between Jan 8, 2013, and Aug 1, 2014, 327 patients were randomly assigned to pacritinib (n = 220) or BAT (n = 107). Median follow-up was 23.2 months (IQR 14.8-28.7). At week 24, the primary endpoint of SVR of 35% or more was achieved by 42 (19%) patients in the pacritinib group versus five (5%) patients in the BAT group (p = 0.0003). 90 patients in the BAT group crossed over to receive pacritinib at a median of 6.3 months (IQR 5.8-6.7). The most common grade 3-4 adverse events through week 24 were anaemia (n = 37 [17%]), thrombocytopenia (n = 26 [12%]), and diarrhoea (n = 11 [5%]) in the pacritinib group, and anaemia (n = 16 [15%]), thrombocytopenia (n = 12 [11%]), dyspnoea (n = 3 [3%]), and hypotension (n = 3 [3%]) in the BAT group. The most common serious adverse events that occurred through week 24 were anaemia (10 [5%]), cardiac failure (5 [2%]), pyrexia (4 [2%]), and pneumonia (4 [2%]) with pacritinib, and anaemia (5 [5%]), sepsis (2 [2%]), and dyspnoea (2 [2%]) with BAT. Deaths due to adverse events were observed in 27 (12%) patients in the pacritinib group and 14 (13%) patients in the BAT group throughout the duration of the study. Interpretation Pacritinib therapy was well tolerated and induced significant and sustained SVR and symptom reduction, even in patients with severe baseline cytopenias. Pacritinib could be a treatment option for patients with myelofibrosis, including those with baseline cytopenias for whom options are particularly limited.
ER  -

MESA, R.A., A.M. VANNUCCHI, A. MEAD, M. EGYED, A. SZOKE, A. SUVOROV, J. JAKUCS, A. PERKINS, R. PRASAD, Jiří MAYER, J. DEMETER, P. GANLY, J.W. SINGER, H.F. ZHOU, JP DEAN, P.A. te BOEKHORST, J. NANGALIA, J.J. KILADJIAN and C.N. HARRISON. Pacritinib versus best available therapy for the treatment of myelofibrosis irrespective of baseline cytopenias (PERSIST-1): an international, randomised, phase 3 trial. \textit{The Lancet. Haematology}. England: ELSEVIER SCI LTD, 2017, vol.~4, No~5, p.~''E225''-''E236'', 12 pp. ISSN~2352-3026. Available from: https://dx.doi.org/10.1016/S2352-3026(17)30027-3.

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