Clonal evolution and outcomes in myelofibrosis after ruxolitinib discontinuation

Kate J. Newberry, Keyur Patel, Lucia Masarova, Rajyalakshmi Luthra, Taghi Manshouri, Elias Jabbour, Prithviraj Bose, Naval Daver, Jorge Cortes, Hagop Kantarjian, Srdan Verstovsek

Research output: Contribution to journalArticle

Abstract

Despite significant improvements in the signs and symptoms of myelofibrosis (MF), and possible prolongation of patients’ survival, some have disease that is refractory to ruxolitinib and many lose their response over time. Furthermore, patients with ≥3 mutations are less likely to respond to ruxolitinib. Here we describe outcomes after ruxolitinib discontinuation in MF patients enrolled in a phase 1/2 study at our center. After a median follow-up of 79 months, 86 patients had discontinued ruxolitinib (30 of whom died while on therapy). The median follow-up after ruxolitinib discontinuation for the remaining 56 patients was 32 months, with median survival after discontinuation of 14 months. Platelets <260 x 109/L at the start of therapy or <100 x 109/L at the time of discontinuation were associated with shorter survival after discontinuation. Of 62 patients with molecular data at baseline and follow-up, 22 (35%) acquired a new mutation while receiving ruxolitinib (14 [61%] in ASXL1). Patients showing clonal evolution had significantly shorter survival after discontinuation (6 vs 16 months). Transfusion dependency was the only clinical variable associated with clonal evolution. These findings underscore the need for novel therapies and suggest that clonal evolution or decreasing platelet counts while on ruxolitinib therapy may be markers of poor prognosis.

Original languageEnglish (US)
Pages (from-to)1125-1131
Number of pages7
JournalBlood
Volume130
Issue number9
DOIs
StatePublished - Aug 31 2017
Externally publishedYes

Fingerprint

Clonal Evolution
Primary Myelofibrosis
Survival
Platelets
Mutation
Therapeutics
INCB018424
Platelet Count
Refractory materials
Signs and Symptoms
Blood Platelets

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Newberry, K. J., Patel, K., Masarova, L., Luthra, R., Manshouri, T., Jabbour, E., ... Verstovsek, S. (2017). Clonal evolution and outcomes in myelofibrosis after ruxolitinib discontinuation. Blood, 130(9), 1125-1131. https://doi.org/10.1182/blood-2017-05-783225

Clonal evolution and outcomes in myelofibrosis after ruxolitinib discontinuation. / Newberry, Kate J.; Patel, Keyur; Masarova, Lucia; Luthra, Rajyalakshmi; Manshouri, Taghi; Jabbour, Elias; Bose, Prithviraj; Daver, Naval; Cortes, Jorge; Kantarjian, Hagop; Verstovsek, Srdan.

In: Blood, Vol. 130, No. 9, 31.08.2017, p. 1125-1131.

Research output: Contribution to journalArticle

Newberry, KJ, Patel, K, Masarova, L, Luthra, R, Manshouri, T, Jabbour, E, Bose, P, Daver, N, Cortes, J, Kantarjian, H & Verstovsek, S 2017, 'Clonal evolution and outcomes in myelofibrosis after ruxolitinib discontinuation', Blood, vol. 130, no. 9, pp. 1125-1131. https://doi.org/10.1182/blood-2017-05-783225
Newberry KJ, Patel K, Masarova L, Luthra R, Manshouri T, Jabbour E et al. Clonal evolution and outcomes in myelofibrosis after ruxolitinib discontinuation. Blood. 2017 Aug 31;130(9):1125-1131. https://doi.org/10.1182/blood-2017-05-783225
Newberry, Kate J. ; Patel, Keyur ; Masarova, Lucia ; Luthra, Rajyalakshmi ; Manshouri, Taghi ; Jabbour, Elias ; Bose, Prithviraj ; Daver, Naval ; Cortes, Jorge ; Kantarjian, Hagop ; Verstovsek, Srdan. / Clonal evolution and outcomes in myelofibrosis after ruxolitinib discontinuation. In: Blood. 2017 ; Vol. 130, No. 9. pp. 1125-1131.
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