Francesca Palandri1, Mario Tiribelli2, Massimo Breccia3, Daniela Bartoletti1,4, Elena M Elli5, Giulia Benevolo6, Bruno Martino7, Francesco Cavazzini8, Alessia Tieghi9, Alessandra Iurlo10, Elisabetta Abruzzese11, Novella Pugliese12, Gianni Binotto13, Giovanni Caocci14, Giuseppe Auteri1,4, Daniele Cattaneo10, Malgorzata M Trawinska11, Rossella Stella2, Luigi Scaffidi15, Nicola Polverelli16, Giorgia Micucci17, Elena Masselli18, Monica Crugnola18, Costanza Bosi19, Florian H Heidel20, Roberto Latagliata21, Fabrizio Pane12, Antonio Cuneo8, Mauro Krampera15, Gianpietro Semenzato13, Roberto M Lemoli22,23, Michele Cavo1,4, Nicola Vianelli1, Massimiliano Bonifacio15, Giuseppe A Palumbo24. 1. Istituto di Ematologia "Seràgnoli," IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy. 2. Division of Hematology and Bone Marrow Transplantation, Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy. 3. Division of Cellular Biotechnologies and Hematology, University Sapienza, Rome, Italy. 4. Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, Bologna, Italy. 5. Hematology Division and Bone Marrow Unit, San Gerardo Hospital, Azienda Socio Sanitaria Territoriale Monza, Monza, Italy. 6. Division of Hematology, Città della Salute e della Scienza Hospital, Turin, Italy. 7. Division of Hematology, Azienda Ospedaliera "Bianchi Melacrino Morelli", Reggio Calabria, Italy. 8. Division of Hematology, University of Ferrara, Ferrara, Italy. 9. Department of Hematology, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy. 10. Hematology Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 11. Division of Hematology, Ospedale S. Eugenio, Rome, Italy. 12. Department of Clinical Medicine and Surgery, Federico II University Medical School, Naples, Italy. 13. Unit of Hematology and Clinical Immunology, University of Padua, Padua, Italy. 14. Ematologia, Ospedale Businco, Università degli Studi di Cagliari, Cagliari, Italy. 15. Section of Hematology, University of Verona, Verona, Italy. 16. Unit of Blood Diseases and Stem Cell Transplantation, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Brescia, Italy. 17. Hematology and Stem Cell Transplant Center, Azienda Ospedaliera Ospedali Riuniti Marche Nord, Pesaro, Italy. 18. Department of Medicine and Surgery, University of Parma, Parma, Italy. 19. Division of Hematology, AUSL di Piacenza, Piacenza, Italy. 20. Hematology and Oncology, Friedrich Schiller University Medical Center, Jena, Germany. 21. Hematology Unit, Ospedale Belcolle, Viterbo, Italy. 22. Clinic of Hematology, Department of Internal Medicine, University of Genoa, Genoa, Italy. 23. IRCCS Policlinico San Martino, Genova, Italy. 24. Department of Scienze Mediche, Chirurgiche e Tecnologie Avanzate "G. F. Ingrassia," University of Catania, Italy.
Abstract
BACKGROUND: After ruxolitinib discontinuation, the outcome of patients with myelofibrosis (MF) is poor with scarce therapeutic possibilities. METHODS: The authors performed a subanalysis of an observational, retrospective study (RUX-MF) that included 703 MF patients treated with ruxolitinib to investigate 1) the frequency and reasons for ruxolitinib rechallenge, 2) its therapeutic effects, and 3) its impact on overall survival. RESULTS: A total of 219 patients (31.2%) discontinued ruxolitinib for ≥14 days and survived for ≥30 days. In 60 patients (27.4%), ruxolitinib was rechallenged for ≥14 days (RUX-again patients), whereas 159 patients (72.6%) discontinued it permanently (RUX-stop patients). The baseline characteristics of the 2 cohorts were comparable, but discontinuation due to a lack/loss of spleen response was lower in RUX-again patients (P = .004). In comparison with the disease status at the first ruxolitinib stop, at its restart, there was a significant increase in patients with large splenomegaly (P < .001) and a high Total Symptom Score (TSS; P < .001). During the rechallenge, 44.6% and 48.3% of the patients had spleen and symptom improvements, respectively, with a significant increase in the number of patients with a TSS reduction (P = .01). Although the use of a ruxolitinib dose > 10 mg twice daily predicted better spleen (P = .05) and symptom improvements (P = .02), the reasons for/duration of ruxolitinib discontinuation and the use of other therapies before rechallenge were not associated with rechallenge efficacy. At 1 and 2 years, 33.3% and 48.3% of RUX-again patients, respectively, had permanently discontinued ruxolitinib. The median overall survival was 27.9 months, and it was significantly longer for RUX-again patients (P = .004). CONCLUSIONS: Ruxolitinib rechallenge was mainly used in intolerant patients; there were clinical improvements and a possible survival advantage in many cases, but there was a substantial rate of permanent discontinuation. Ruxolitinib rechallenge should be balanced against newer therapeutic possibilities.
BACKGROUND: After ruxolitinib discontinuation, the outcome of patients with myelofibrosis (MF) is poor with scarce therapeutic possibilities. METHODS: The authors performed a subanalysis of an observational, retrospective study (RUX-MF) that included 703 MF patients treated with ruxolitinib to investigate 1) the frequency and reasons for ruxolitinib rechallenge, 2) its therapeutic effects, and 3) its impact on overall survival. RESULTS: A total of 219 patients (31.2%) discontinued ruxolitinib for ≥14 days and survived for ≥30 days. In 60 patients (27.4%), ruxolitinib was rechallenged for ≥14 days (RUX-again patients), whereas 159 patients (72.6%) discontinued it permanently (RUX-stop patients). The baseline characteristics of the 2 cohorts were comparable, but discontinuation due to a lack/loss of spleen response was lower in RUX-again patients (P = .004). In comparison with the disease status at the first ruxolitinib stop, at its restart, there was a significant increase in patients with large splenomegaly (P < .001) and a high Total Symptom Score (TSS; P < .001). During the rechallenge, 44.6% and 48.3% of the patients had spleen and symptom improvements, respectively, with a significant increase in the number of patients with a TSS reduction (P = .01). Although the use of a ruxolitinib dose > 10 mg twice daily predicted better spleen (P = .05) and symptom improvements (P = .02), the reasons for/duration of ruxolitinib discontinuation and the use of other therapies before rechallenge were not associated with rechallenge efficacy. At 1 and 2 years, 33.3% and 48.3% of RUX-again patients, respectively, had permanently discontinued ruxolitinib. The median overall survival was 27.9 months, and it was significantly longer for RUX-again patients (P = .004). CONCLUSIONS: Ruxolitinib rechallenge was mainly used in intolerant patients; there were clinical improvements and a possible survival advantage in many cases, but there was a substantial rate of permanent discontinuation. Ruxolitinib rechallenge should be balanced against newer therapeutic possibilities.