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 / F. Palandri, M. Tiribelli, M. Breccia, D. Bartoletti, E.M. Elli, G. Benevolo, B. Martino, F. Cavazzini, A. Tieghi, A. Iurlo, E. Abruzzese, N. Pugliese, G. Binotto, G. Caocci, G. Auteri, D. Cattaneo, M.M. Trawinska, R. Stella, L. Scaffidi, N. Polverelli, G. Micucci, E. Masselli, M. Crugnola, C. Bosi, F.H. Heidel, R. Latagliata, F. Pane, A. Cuneo, M. Krampera, G. Semenzato, R.M. Lemoli, M. Cavo, N. Vianelli, M. Bonifacio, G.A. Palumbo. - In: CANCER. - ISSN 0008-543X. - 127:15(2021 Aug 01), pp. 2657-2665. [10.1002/cncr.33541]

Ruxolitinib rechallenge in resistant or intolerant patients with myelofibrosis : Frequency, therapeutic effects, and impact on outcome

D. Cattaneo;
2021-08-01

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.
cancer; myelofibrosis; outcome; rechallenge; ruxolitinib
Settore MED/15 - Malattie del Sangue
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/859584
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