Francesca Palandri1, Massimo Breccia2, Massimiliano Bonifacio3, Nicola Polverelli4, Elena M Elli5, Giulia Benevolo6, Mario Tiribelli7, Elisabetta Abruzzese8, Alessandra Iurlo9, Florian H Heidel10, Micaela Bergamaschi11, Alessia Tieghi12, Monica Crugnola13, Francesco Cavazzini14, Gianni Binotto15, Alessandro Isidori16, Nicola Sgherza17, Costanza Bosi18, Bruno Martino19, Roberto Latagliata2, Giuseppe Auteri1, Luigi Scaffidi3, Davide Griguolo7, Malgorzata Trawinska8, Daniele Cattaneo9, Lucia Catani1, Mauro Krampera3, Roberto M Lemoli11, Antonio Cuneo14, Gianpietro Semenzato15, Robin Foà2, Francesco Di Raimondo20, Daniela Bartoletti1, Michele Cavo1, Giuseppe A Palumbo21, Nicola Vianelli1. 1. Institute of Hematology "L. and A. Seràgnoli", St Orsola-Malpighi University Hospital, Bologna, Italy. 2. Division of Cellular Biotechnology and Hematology, Sapienza University, Rome, Italy. 3. Department of Medicine, Section of Hematology, University of Verona, Verona, Italy. 4. Unit of Blood Diseases and Stem Cell Transplantation, Department of Clinical and Experimental Sciences, University of Brescia, ASST-Spedali Civili di Brescia, Brescia, Italy. 5. Hematology Division and Bone Marrow Unit, San Gerardo Hospital, Monza, Italy. 6. Division of Hematology, City Hospital of Health and Science, Turin, Italy. 7. Division of Hematology and Bone Marrow Transplantation, Integrated Healthcare University of Udine, Udine, Italy. 8. Division of Hematology, St Eugene Hospital, Rome, Italy. 9. Hematology Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico and University of Milan, Milan, Italy. 10. Internal Medicine II, Hematology and Oncology, Friedrich Schiller University Medical Center, Jena, Germany. 11. Clinic of Hematology, Department of Internal Medicine, IRCCS San Martino Hospital, University of Genoa, Genoa, Italy. 12. Hematology Unit, Azienda Unità Sanitaria Locale - IRCCS, Arcispedale S.Maria Nuova, Reggio Emilia, Italy. 13. Division of Hematology, University Hospital of Parma, Parma, Italy. 14. Division of Hematology, University of Ferrara, Ferrara, Italy. 15. Unit of Hematology and Clinical Immunology, University of Padua, Padua, Italy. 16. Hematology and Stem Cell Transplantation Center, Azienda Ospedaliera Ospedali Riuniti Marche Nord (AORMN), Pesaro, Italy. 17. Division of Hematology, Home for the Relief of Suffering, San Giovanni Rotondo, Italy. 18. Division of Hematology, Local Healthcare Unit of Piacenza, Piacenza, Italy. 19. Division of Hematology, "Bianchi Melacrino Morelli" Hospital Corporation, Reggio Calabria, Italy. 20. Division of Hematology, V. Emanuele University Polyclinic, University of Catania, Catania, Italy. 21. Department of Medical Science, Surgery, and Advanced Technology "G. F. Ingrassia", University of Catania, Catania, Italy.
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.
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.
Authors: Aaron T Gerds; Michael R Savona; Bart L Scott; Moshe Talpaz; Miklos Egyed; Claire N Harrison; Abdulraheem Yacoub; Alessandro Vannucchi; Adam J Mead; Jean-Jacques Kiladjian; Jennifer O'Sullivan; Valentin García-Gutiérrez; Prithviraj Bose; Raajit K Rampal; Carole B Miller; Jeanne Palmer; Stephen T Oh; Sarah A Buckley; Diane R Mould; Kaori Ito; Shanthakumar Tyavanagimatt; Jennifer A Smith; Karisse Roman-Torres; Sri Devineni; Adam R Craig; John O Mascarenhas Journal: Blood Adv Date: 2020-11-24
Authors: Claire N Harrison; Nicolaas Schaap; Alessandro M Vannucchi; Jean-Jacques Kiladjian; Eric Jourdan; Richard T Silver; Harry C Schouten; Francesco Passamonti; Sonja Zweegman; Moshe Talpaz; Srdan Verstovsek; Shelonitda Rose; Juan Shen; Tymara Berry; Carrie Brownstein; Ruben A Mesa Journal: Am J Hematol Date: 2020-04-17 Impact factor: 10.047