Background: Patients with cytopenic myelofibrosis (MF) have more limited therapeutic options and poorer prognoses compared with patients with the myeloproliferative phenotype. Aims and Methods: Prognostic correlates of cytopenic phenotype were explored in 886 ruxolitinib-treated patients with primary/secondary MF (PMF/SMF) included in the RUX-MF retrospective study. Cytopenia was defined as: leukocyte count <4 × 109/L and/or hemoglobin <11/<10 g/dL (males/females) and/or platelets <100 × 109/L. Results: Overall, 407 (45.9%) patients had a cytopenic MF, including 249 (52.4%) with PMF. In multivariable analysis, high molecular risk mutations (p =.04), intermediate 2/high Dynamic International Prognostic Score System (p <.001) and intermediate 2/high Myelofibrosis Secondary to Polycythemia Vera and Essential Thrombocythemia Prognostic Model (p <.001) remained associated with cytopenic MF in the overall cohort, PMF, and SMF, respectively. Patients with cytopenia received lower average ruxolitinib at the starting (25.2 mg/day vs. 30.2 mg/day, p <.001) and overall doses (23.6 mg/day vs. 26.8 mg/day, p <.001) and achieved lower rates of spleen (26.5% vs. 34.1%, p =.04) and symptom (59.8% vs. 68.8%, p =.008) responses at 6 months compared with patients with the proliferative phenotype. Patients with cytopenia also had higher rates of thrombocytopenia at 3 months (31.1% vs. 18.8%, p <.001) but lower rates of anemia (65.6% vs. 57.7%, p =.02 at 3 months and 56.6% vs. 23.9% at 6 months, p <.001). After competing risk analysis, the cumulative incidence of ruxolitinib discontinuation at 5 years was 57% and 38% in patients with cytopenia and the proliferative phenotype (p <.001), whereas cumulative incidence of leukemic transformation was similar (p =.06). In Cox regression analysis adjusted for Dynamic International Prognostic Score System score, survival was significantly shorter in patients with cytopenia (p <.001). Conclusions: Cytopenic MF has a lower probability of therapeutic success with ruxolitinib as monotherapy and worse outcome. These patients should be considered for alternative therapeutic strategies.
Ruxolitinib in cytopenic myelofibrosis: Response, toxicity, drug discontinuation, and outcome / Palandri F.; Breccia M.; Mazzoni C.; Auteri G.; Elli E.M.; Trawinska M.M.; Polverelli N.; Tiribelli M.; Benevolo G.; Iurlo A.; Tieghi A.; Heidel F.H.; Caocci G.; Beggiato E.; Binotto G.; Cavazzini F.; Miglino M.; Bosi C.; Crugnola M.; Bocchia M.; Martino B.; Pugliese N.; Biondo M.; Venturi M.; Scaffidi L.; Isidori A.; Cattaneo D.; Krampera M.; Pane F.; Cilloni D.; Semenzato G.; Lemoli R.M.; Cuneo A.; Abruzzese E.; Bartoletti D.; Paglia S.; Vianelli N.; Cavo M.; Bonifacio M.; Palumbo G.A.. - In: CANCER. - ISSN 0008-543X. - STAMPA. - 129:11(2023), pp. 1704-1713. [10.1002/cncr.34722]
Ruxolitinib in cytopenic myelofibrosis: Response, toxicity, drug discontinuation, and outcome
Palandri F.
;Mazzoni C.;Auteri G.;Biondo M.;Venturi M.;Bartoletti D.;Paglia S.;Vianelli N.;Cavo M.;Palumbo G. A.
2023
Abstract
Background: Patients with cytopenic myelofibrosis (MF) have more limited therapeutic options and poorer prognoses compared with patients with the myeloproliferative phenotype. Aims and Methods: Prognostic correlates of cytopenic phenotype were explored in 886 ruxolitinib-treated patients with primary/secondary MF (PMF/SMF) included in the RUX-MF retrospective study. Cytopenia was defined as: leukocyte count <4 × 109/L and/or hemoglobin <11/<10 g/dL (males/females) and/or platelets <100 × 109/L. Results: Overall, 407 (45.9%) patients had a cytopenic MF, including 249 (52.4%) with PMF. In multivariable analysis, high molecular risk mutations (p =.04), intermediate 2/high Dynamic International Prognostic Score System (p <.001) and intermediate 2/high Myelofibrosis Secondary to Polycythemia Vera and Essential Thrombocythemia Prognostic Model (p <.001) remained associated with cytopenic MF in the overall cohort, PMF, and SMF, respectively. Patients with cytopenia received lower average ruxolitinib at the starting (25.2 mg/day vs. 30.2 mg/day, p <.001) and overall doses (23.6 mg/day vs. 26.8 mg/day, p <.001) and achieved lower rates of spleen (26.5% vs. 34.1%, p =.04) and symptom (59.8% vs. 68.8%, p =.008) responses at 6 months compared with patients with the proliferative phenotype. Patients with cytopenia also had higher rates of thrombocytopenia at 3 months (31.1% vs. 18.8%, p <.001) but lower rates of anemia (65.6% vs. 57.7%, p =.02 at 3 months and 56.6% vs. 23.9% at 6 months, p <.001). After competing risk analysis, the cumulative incidence of ruxolitinib discontinuation at 5 years was 57% and 38% in patients with cytopenia and the proliferative phenotype (p <.001), whereas cumulative incidence of leukemic transformation was similar (p =.06). In Cox regression analysis adjusted for Dynamic International Prognostic Score System score, survival was significantly shorter in patients with cytopenia (p <.001). Conclusions: Cytopenic MF has a lower probability of therapeutic success with ruxolitinib as monotherapy and worse outcome. These patients should be considered for alternative therapeutic strategies.| File | Dimensione | Formato | |
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Cancer - 2023 - Palandri - Ruxolitinib in cytopenic myelofibrosis Response toxicity drug discontinuation and outcome.pdf
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