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 F.;Bartoletti D.;Auteri G.;Lemoli R. M.;Cavo M.;Vianelli N.;
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.
Palandri F.; Tiribelli M.; Breccia M.; Bartoletti D.; Elli E.M.; Benevolo G.; Martino B.; Cavazzini F.; Tieghi A.; Iurlo A.; Abruzzese E.; Pugliese N.; Binotto G.; Caocci G.; Auteri G.; Cattaneo D.; Trawinska M.M.; Stella R.; Scaffidi L.; Polverelli N.; Micucci G.; Masselli E.; Crugnola M.; Bosi C.; Heidel F.H.; Latagliata R.; Pane F.; Cuneo A.; Krampera M.; Semenzato G.; Lemoli R.M.; Cavo M.; Vianelli N.; Bonifacio M.; Palumbo G.A.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/865040
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