Primary analysis of JUMP, a phase 3b, expanded‐access study evaluating the safety and efficacy of ruxolitinib in patients with myelofibrosis, including those with low platelet counts

British Journal of Haematology - Tập 189 Số 5 - Trang 888-903 - 2020
Haifa Kathrin Al‐Ali1, Martin Grießhammer2, Lynda Foltz3, Giuseppe A. Palumbo4, Bruno Martino5, Francesca Palandri6, Anna Marina Liberati7, Philipp le Coutre8, Carmen García‐Hernández9, Andrey Zaritskey10, Renato Tavares Daher11, Vikas Gupta12, Pia Raanani13, Pilar Giraldo14, Mathias Hänel15, Daniela Damiani16, Tomasz Sacha17, Catherine Bouard18, Carole Paley19, Ranjan Tiwari20, Francesco Mannelli21, Alessandro M. Vannucchi21
1Universitätsklinikum Halle, Halle (Saale), Germany
2Johannes Wesling Medical Center Minden, University Clinic for Hematology, Oncology, Hemostaseology, and Palliative Care, UKRUB, University of Bochum, Minden, Germany
3St Paul’s Hospital, University of British Columbia, Vancouver, BC, Canada
4Dipartimento di Scienze Mediche, Chirurgiche E Tecnologie Avanzate “G.F. Ingrassia”, University of Catania, Catania, Italy
5Azienda Ospedaliera “Bianchi Melacrino Morelli”, Reggio Calabria, Italy
6Department of Hematology/Oncology “Seràgnoli” Institute of Hematology University of Bologna School of Medicine Bologna Italy
7University of Perugia, Azienda Ospedaliera S. Maria, Terni, Italy
8Charité – Universitätsmedizin Berlin, Berlin, Germany
9Hospital General de Alicante, Alicante, Spain
10Almazov National Medical Research Centre, St. Petersburg, Russia
11Universidade Federal de Goiás, Goiás, Brazil
12Princess Margaret Cancer Centre, Toronto, ON, Canada
13Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
14Miguel Servet University Hospital and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Zaragoza, Spain
15Klinikum Chemnitz gGmbH, Chemnitz, Germany
16University of Udine, Udine, Italy
17Jagiellonian University, Kraków, Poland
18Novartis Pharma S.A.S., Rueil-Malmaison, France
19Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA
20Novartis Healthcare Pvt. Ltd., Hyderabad, India
21Center for Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Florence, Italy

Tóm tắt

Summary

Ruxolitinib is a potent Janus kinase (JAK) 1/JAK2 inhibitor approved for the treatment of myelofibrosis (MF). Ruxolitinib was assessed in JUMP, a large (N = 2233), phase 3b, expanded‐access study in MF in countries without access to ruxolitinib outside a clinical trial, which included patients with low platelet counts (<100 × 109/l) and patients without splenomegaly – populations that have not been extensively studied. The most common adverse events (AEs) were anaemia and thrombocytopenia, but they rarely led to discontinuation (overall, 5·4%; low‐platelet cohort, 12·3%). As expected, rates of worsening thrombocytopenia were higher in the low‐platelet cohort (all grades, 73·2% vs. 53·5% overall); rates of anaemia were similar (all grades, 52·9% vs. 59·5%). Non‐haematologic AEs, including infections, were mainly grade 1/2. Overall, ruxolitinib led to meaningful reductions in spleen length and symptoms, including in patients with low platelet counts, and symptom improvements in patients without splenomegaly. In this trial, the largest study of ruxolitinib in patients with MF to date, the safety profile was consistent with previous reports, with no new safety concerns identified. This study confirms findings from the COMFORT studies and supports the use of ruxolitinib in patients with platelet counts of 50–100 × 109/l. (ClinicalTrials.gov identifier NCT01493414).

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Tài liệu tham khảo

10.3324/haematol.2016.143677

10.1038/sj.leu.2404914

10.1182/blood.V112.11.2376.2376

10.1016/S0885-3924(02)00529-8

10.1182/blood-2008-07-170449

10.1182/blood-2013-02-485888

10.1200/JCO.2012.42.3863

10.1182/blood-2013-09-527903

Gupta V. Griesshammer M. Martino B. Foltz L. Tavares R. Al‐Ali H.K. Giraldo P. Guglielmelli P. Lomaia E. Bouard C. Perez Ronco J. Tiwari R.&Raanani P.(2017)Predictors of response to ruxolitinib in patients with myelofibrosis in the phase 3b expanded‐access JUMP study PF616.

10.1056/NEJMoa1110556

10.1038/leu.2016.148

10.1007/s00277-017-3082-y

10.1177/1179545X17695233

Jakafi (ruxolitinib)(2017)package insert.Incyte Corporation Wilmington Delaware USA.

Jakavi (ruxolitinib)(2016)[summary of product characteristics].Novartis Pharmaceuticals UK Limited Horsham West Sussex UK.

10.1038/s41375-018-0027-y

10.1186/s12885-016-2208-2

10.18632/oncotarget.18674

10.1182/blood-2009-09-245837

Passamonti F., 2017, Comparing the safety and efficacy of ruxolitinib (RUX) in patients (PTS) with DIPSS low/intermediate‐1–, intermediate‐2–, and high‐risk myelofibrosis (MF) in JUMP, a phase 3B, expanded‐access study, Haematologica, 102, E1333

10.1182/blood-2016-10-695957

10.1186/1756-8722-6-81

10.1002/ajh.23703

10.1002/ajh.24592

10.3324/haematol.2014.119545

10.3324/haematol.2018.204602

10.1182/blood-2009-03-209262

10.1056/NEJMoa1110557

10.2147/OTT.S53348

10.1186/s13045-017-0527-7

10.1186/s13045-017-0417-z

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British Journal of Haematology

Tập 189 Số 5

888-903

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