Life after ruxolitinib: Reasons for discontinuation, impact of disease phase, and outcomes in 218 patients with myelofibrosis

Francesca Palandri, Massimo Breccia, Massimiliano Bonifacio, Nicola Polverelli, Elena M. Elli, Giulia Benevolo, Mario Tiribelli, Elisabetta Abruzzese, Alessandra Iurlo, Florian H. Heidel, Micaela Bergamaschi, Alessia Tieghi, Monica Crugnola, Francesco Cavazzini, Gianni Binotto, Alessandro Isidori, Nicola Sgherza, Costanza Bosi, Bruno Martino, Roberto LatagliataGiuseppe Auteri, Luigi Scaffidi, Davide Griguolo, Malgorzata Trawinska, Daniele Cattaneo, Lucia Catani, Mauro Krampera, Roberto M. Lemoli, Antonio Cuneo, Gianpietro Semenzato, Robin Foà, Francesco Di Raimondo, Daniela Bartoletti, Michele Cavo, Giuseppe A. Palumbo, Nicola Vianelli

Research output: Contribution to journalArticlepeer-review

Abstract

Background: After discontinuing ruxolitinib, the outcome of patients with myelofibrosis reportedly has been poor. The authors investigated whether disease characteristics before the receipt of ruxolitinib may predict drug discontinuation in patients with myelofibrosis and whether reasons for drug discontinuation, disease phase at discontinuation, and salvage therapies may influence the outcome. Methods: A centralized electronic clinical database was created in 20 European hematology centers, including clinical and laboratory data for 524 patients who received ruxolitinib for myelofibrosis. Results: At 3 years, 40.8% of patients had stopped ruxolitinib. Baseline predictors of drug discontinuation were: intermediate-2–risk/high-risk category (Dynamic International Prognostic Score System), a platelet count <100 ×109 per liter, transfusion dependency, and unfavorable karyotype. At last contact, 268 patients (51.1%) had discontinued therapy, and the median drug exposure was 17.5 months. Fifty patients (18.7%) died while taking ruxolitinib. The reasons for discontinuation in the remaining 218 patients were the lack (22.9%) or loss (11.9%) of a spleen response, ruxolitinib-related adverse events (27.5%), progression to blast phase (23.4%), ruxolitinib-unrelated adverse events (9.2%), and allogeneic transplantation during response (5.1%). The median survival after ruxolitinib was 13.2 months and was significantly better in the 167 patients who discontinued ruxolitinib in chronic phase (27.5 vs 3.9 months for those who discontinued in blast phase; P <.001). No survival differences were observed among patients who discontinued ruxolitinib in chronic phase because of lack of response, loss of response, or ruxolitinib-related adverse events. The use of investigational agents and/or ruxolitinib rechallenge were associated with improved outcome. Conclusions: The survival of patients with myelofibrosis after discontinuation of ruxolitinib is poor, particularly for those who discontinue in blast phase. Salvage therapies can improve outcome, emphasizing the need for novel therapies.

Original languageEnglish
JournalCancer
DOIs
Publication statusAccepted/In press - Jan 1 2019

Keywords

  • investigational agents
  • myelofibrosis
  • outcome
  • ruxolitinib
  • treatment failure

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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