Skip to main content
Erschienen in: Annals of Hematology 1/2021

20.10.2020 | Original Article

Low-dose ruxolitinib shows effective in treating myelofibrosis

verfasst von: Yunfan Yang, Hongmei Luo, Yuhuan Zheng, Zhongqing Zou, Ting Niu, Yongqian Jia, Huanling Zhu, Ting Liu, Yu Wu, Hong Chang, Jie Ji, Jian Li, Ling Pan

Erschienen in: Annals of Hematology | Ausgabe 1/2021

Einloggen, um Zugang zu erhalten

Abstract

The aim of this study was to investigate the effect of low-dose ruxolitinib (daily dose ≤ 10 mg) for the treatment of myelofibrosis (MF). A retrospective analysis was performed on a total of 88 patients with myeloproliferative neoplasm-associated MF (MPN-MF) who were diagnosed and treated in West China Hospital, Sichuan University, China. A total of 44 MPN-MF patients received a low dose of ruxolitinib (daily dose ≤ 10 mg), while another 44 patients received 10–25 mg twice daily. Low-dose ruxolitinib treatment resulted in slow, but gradual spleen response. Compared with baseline, the mean changes in palpable spleen length in the low- and high-dose groups were −26.9 and −49.0% after 12 weeks of treatment, respectively, and −46.7 and −64.1% after 48 weeks of treatment, respectively. In the low dose group, the median myeloproliferative neoplasm symptom assessment form (MPN-SAF) total symptom score (TSS) decreased by 37.8 and 35.9% at the 12 weeks and 48 weeks after treatment, respectively. No statistical difference was observed in MPN-SAF TSS among different dose groups. After 48 weeks of treatment, bone marrow (BM) fibrosis improved in 43.3% (13/30) of evaluated patients and was stable in 56.7% (17/30) patients. In the low-dose treated group, BM fibrosis improved in 50% patients and was stable in remaining 50%. Low-dose ruxolitinib is effective in treating MF.
Literatur
4.
Zurück zum Zitat Gregory SA, Mesa RA, Hoffman R, Shammo JM (2011) Clinical and laboratory features of myelofibrosis and limitations of current therapies. Clin Adv Hematol Oncol 9(9 Suppl 22):1–16PubMed Gregory SA, Mesa RA, Hoffman R, Shammo JM (2011) Clinical and laboratory features of myelofibrosis and limitations of current therapies. Clin Adv Hematol Oncol 9(9 Suppl 22):1–16PubMed
5.
Zurück zum Zitat Cervantes F, Dupriez B, Pereira A, Passamonti F, Reilly JT, Morra E, Vannucchi AM, Mesa RA, Demory JL, Barosi G, Rumi E, Tefferi A (2009) New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood 113(13):2895–2901. https://doi.org/10.1182/blood-2008-07-170449CrossRefPubMed Cervantes F, Dupriez B, Pereira A, Passamonti F, Reilly JT, Morra E, Vannucchi AM, Mesa RA, Demory JL, Barosi G, Rumi E, Tefferi A (2009) New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood 113(13):2895–2901. https://​doi.​org/​10.​1182/​blood-2008-07-170449CrossRefPubMed
8.
Zurück zum Zitat Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, Catalano JV, Deininger M, Miller C, Silver RT, Talpaz M, Winton EF, Harvey JH Jr, Arcasoy MO, Hexner E, Lyons RM, Paquette R, Raza A, Vaddi K, Erickson-Viitanen S, Koumenis IL, Sun W, Sandor V, Kantarjian HM (2012) A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med 366(9):799–807. https://doi.org/10.1056/NEJMoa1110557CrossRefPubMedPubMedCentral Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, Catalano JV, Deininger M, Miller C, Silver RT, Talpaz M, Winton EF, Harvey JH Jr, Arcasoy MO, Hexner E, Lyons RM, Paquette R, Raza A, Vaddi K, Erickson-Viitanen S, Koumenis IL, Sun W, Sandor V, Kantarjian HM (2012) A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med 366(9):799–807. https://​doi.​org/​10.​1056/​NEJMoa1110557CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Harrison C, Kiladjian JJ, Al-Ali HK, Gisslinger H, Waltzman R, Stalbovskaya V, McQuitty M, Hunter DS, Levy R, Knoops L, Cervantes F, Vannucchi AM, Barbui T, Barosi G (2012) JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med 366(9):787–798. https://doi.org/10.1056/NEJMoa1110556CrossRefPubMed Harrison C, Kiladjian JJ, Al-Ali HK, Gisslinger H, Waltzman R, Stalbovskaya V, McQuitty M, Hunter DS, Levy R, Knoops L, Cervantes F, Vannucchi AM, Barbui T, Barosi G (2012) JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med 366(9):787–798. https://​doi.​org/​10.​1056/​NEJMoa1110556CrossRefPubMed
10.
Zurück zum Zitat Cervantes F, Vannucchi AM, Kiladjian JJ, Al-Ali HK, Sirulnik A, Stalbovskaya V, McQuitty M, Hunter DS, Levy RS, Passamonti F, Barbui T, Barosi G, Harrison CN, Knoops L, Gisslinger H (2013) Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis. Blood 122(25):4047–4053. https://doi.org/10.1182/blood-2013-02-485888CrossRefPubMed Cervantes F, Vannucchi AM, Kiladjian JJ, Al-Ali HK, Sirulnik A, Stalbovskaya V, McQuitty M, Hunter DS, Levy RS, Passamonti F, Barbui T, Barosi G, Harrison CN, Knoops L, Gisslinger H (2013) Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis. Blood 122(25):4047–4053. https://​doi.​org/​10.​1182/​blood-2013-02-485888CrossRefPubMed
13.
Zurück zum Zitat Ward AC, Touw I, Yoshimura A (2000) The Jak-Stat pathway in normal and perturbed hematopoiesis. Blood 95(1):19–29CrossRef Ward AC, Touw I, Yoshimura A (2000) The Jak-Stat pathway in normal and perturbed hematopoiesis. Blood 95(1):19–29CrossRef
15.
17.
Zurück zum Zitat Mesa RA, Dueck AC, Geyer HL, Kiladjian JJ, Slot S, Zweegman S, te Boekhorst PA, Commandeur S, Schouten HC, Sackmann F, Kerguelen Fuentes A, Hernandez-Maraver D, Pahl HL, Griesshammer M, Stegelmann F, Doehner K, Lehmann T, Bonatz K, Reiter A, Boyer F, Etienne G, Ianotto JC, Ranta D, Roy L, Cahn JY, Harrison CN, Radia D, Muxi P, Maldonado N, Besses C, Cervantes F, Johansson PL, Barbui T, Barosi G, Vannucchi AM, Passamonti F, Andreasson B, Ferrari ML, Rambaldi A, Samuelsson J, Birgegard G, Tefferi A, Mesa RA (2012) Myeloproliferative neoplasm (MPN) symptom assessment form total symptom score: prospective international assessment of an abbreviated symptom burden scoring system among patients with MPNs. J Clin Oncol 30(33):4098–4103. https://doi.org/10.1200/JCO.2012.42.3863CrossRefPubMedPubMedCentral Mesa RA, Dueck AC, Geyer HL, Kiladjian JJ, Slot S, Zweegman S, te Boekhorst PA, Commandeur S, Schouten HC, Sackmann F, Kerguelen Fuentes A, Hernandez-Maraver D, Pahl HL, Griesshammer M, Stegelmann F, Doehner K, Lehmann T, Bonatz K, Reiter A, Boyer F, Etienne G, Ianotto JC, Ranta D, Roy L, Cahn JY, Harrison CN, Radia D, Muxi P, Maldonado N, Besses C, Cervantes F, Johansson PL, Barbui T, Barosi G, Vannucchi AM, Passamonti F, Andreasson B, Ferrari ML, Rambaldi A, Samuelsson J, Birgegard G, Tefferi A, Mesa RA (2012) Myeloproliferative neoplasm (MPN) symptom assessment form total symptom score: prospective international assessment of an abbreviated symptom burden scoring system among patients with MPNs. J Clin Oncol 30(33):4098–4103. https://​doi.​org/​10.​1200/​JCO.​2012.​42.​3863CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Barbui T, Tefferi A, Vannucchi AM, Passamonti F, Silver RT, Hoffman R, Verstovsek S, Mesa R, Kiladjian JJ, Hehlmann R, Reiter A, Cervantes F, Harrison C, Mc Mullin MF, Hasselbalch HC, Koschmieder S, Marchetti M, Bacigalupo A, Finazzi G, Kroeger N, Griesshammer M, Birgegard G, Barosi G (2018) Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet. Leukemia 32(5):1057–1069. https://doi.org/10.1038/s41375-018-0077-1CrossRefPubMedPubMedCentral Barbui T, Tefferi A, Vannucchi AM, Passamonti F, Silver RT, Hoffman R, Verstovsek S, Mesa R, Kiladjian JJ, Hehlmann R, Reiter A, Cervantes F, Harrison C, Mc Mullin MF, Hasselbalch HC, Koschmieder S, Marchetti M, Bacigalupo A, Finazzi G, Kroeger N, Griesshammer M, Birgegard G, Barosi G (2018) Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet. Leukemia 32(5):1057–1069. https://​doi.​org/​10.​1038/​s41375-018-0077-1CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Marchetti M, Barosi G, Cervantes F, Birgegard G, Griesshammer M, Harrison C, Hehlmann R, Kiladjian JJ, Kroger N, McMullin MF, Passamonti F, Vannucchi A, Barbui T (2017) Which patients with myelofibrosis should receive ruxolitinib therapy? ELN-SIE evidence-based recommendations. Leukemia 31(4):882–888. https://doi.org/10.1038/leu.2016.283CrossRefPubMed Marchetti M, Barosi G, Cervantes F, Birgegard G, Griesshammer M, Harrison C, Hehlmann R, Kiladjian JJ, Kroger N, McMullin MF, Passamonti F, Vannucchi A, Barbui T (2017) Which patients with myelofibrosis should receive ruxolitinib therapy? ELN-SIE evidence-based recommendations. Leukemia 31(4):882–888. https://​doi.​org/​10.​1038/​leu.​2016.​283CrossRefPubMed
20.
21.
Zurück zum Zitat Palandri F, Palumbo GA, Bonifacio M, Tiribelli M, Benevolo G, Martino B, Abruzzese E, D'Adda M, Polverelli N, Bergamaschi M, Tieghi A, Cavazzini F, Ibatici A, Crugnola M, Bosi C, Latagliata R, Di Veroli A, Scaffidi L, de Marchi F, Cerqui E, Anaclerico B, De Matteis G, Spinsanti M, Sabattini E, Catani L, Aversa F, Di Raimondo F, Vitolo U, Lemoli RM, Fanin R, Merli F, Russo D, Cuneo A, Bacchi Reggiani ML, Cavo M, Vianelli N, Breccia M (2017) Baseline factors associated with response to ruxolitinib: an independent study on 408 patients with myelofibrosis. Oncotarget 8(45):79073–79086. https://doi.org/10.18632/oncotarget.18674CrossRefPubMedPubMedCentral Palandri F, Palumbo GA, Bonifacio M, Tiribelli M, Benevolo G, Martino B, Abruzzese E, D'Adda M, Polverelli N, Bergamaschi M, Tieghi A, Cavazzini F, Ibatici A, Crugnola M, Bosi C, Latagliata R, Di Veroli A, Scaffidi L, de Marchi F, Cerqui E, Anaclerico B, De Matteis G, Spinsanti M, Sabattini E, Catani L, Aversa F, Di Raimondo F, Vitolo U, Lemoli RM, Fanin R, Merli F, Russo D, Cuneo A, Bacchi Reggiani ML, Cavo M, Vianelli N, Breccia M (2017) Baseline factors associated with response to ruxolitinib: an independent study on 408 patients with myelofibrosis. Oncotarget 8(45):79073–79086. https://​doi.​org/​10.​18632/​oncotarget.​18674CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Al-Ali HK, Griesshammer M, Foltz L, Palumbo GA, Martino B, Palandri F, Liberati AM, le Coutre P, García-Hernández C, Zaritskey A, Tavares R, Gupta V, Raanani P, Giraldo P, Hänel M, Damiani D, Sacha T, Bouard C, Paley C, Tiwari R, Mannelli F, Vannucchi AM (2020) 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. Br J Haematol. 189:888–903. https://doi.org/10.1111/bjh.16462CrossRefPubMed Al-Ali HK, Griesshammer M, Foltz L, Palumbo GA, Martino B, Palandri F, Liberati AM, le Coutre P, García-Hernández C, Zaritskey A, Tavares R, Gupta V, Raanani P, Giraldo P, Hänel M, Damiani D, Sacha T, Bouard C, Paley C, Tiwari R, Mannelli F, Vannucchi AM (2020) 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. Br J Haematol. 189:888–903. https://​doi.​org/​10.​1111/​bjh.​16462CrossRefPubMed
Metadaten
Titel
Low-dose ruxolitinib shows effective in treating myelofibrosis
verfasst von
Yunfan Yang
Hongmei Luo
Yuhuan Zheng
Zhongqing Zou
Ting Niu
Yongqian Jia
Huanling Zhu
Ting Liu
Yu Wu
Hong Chang
Jie Ji
Jian Li
Ling Pan
Publikationsdatum
20.10.2020
Verlag
Springer Berlin Heidelberg
Erschienen in
Annals of Hematology / Ausgabe 1/2021
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-020-04311-z

Weitere Artikel der Ausgabe 1/2021

Annals of Hematology 1/2021 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.