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.
Ruxolitinib rechallenge in resistant or intolerant patients with myelofibrosis: Frequency, therapeutic effects, and impact on outcome / Palandri, Francesca; Tiribelli, Mario; Breccia, Massimo; Bartoletti, Daniela; Elli, Elena M.; Benevolo, Giulia; Martino, Bruno; Cavazzini, Francesco; Tieghi, Alessia; Iurlo, Alessandra; Abruzzese, Elisabetta; Pugliese, Novella; Binotto, Gianni; Caocci, Giovanni; Auteri, Giuseppe; Cattaneo, Daniele; Trawinska, Malgorzata M.; Stella, Rossella; Scaffidi, Luigi; Polverelli, Nicola; Micucci, Giorgia; Masselli, Elena; Crugnola, Monica; Bosi, Costanza; Heidel, Florian H.; Latagliata, Roberto; Pane, Fabrizio; Cuneo, Antonio; Krampera, Mauro; Semenzato, Gianpietro; Lemoli, Roberto M.; Cavo, Michele; Vianelli, Nicola; Bonifacio, Massimiliano; Palumbo, Giuseppe A.. - In: CANCER. - ISSN 0008-543X. - 127:15(2021), pp. 2657-2665. [10.1002/cncr.33541]
Ruxolitinib rechallenge in resistant or intolerant patients with myelofibrosis: Frequency, therapeutic effects, and impact on outcome
Breccia, Massimo;
2021
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
