Ruxolitinib in cytopenic myelofibrosis: Response, toxicity, drug discontinuation, and outcome

Palandri, Francesca;Breccia, Massimo;Mazzoni, Camilla;Auteri, Giuseppe;Elli, Elena Maria;Trawinska, Malgorzata M;Polverelli, Nicola;Tiribelli, Mario;Benevolo, Giulia;Iurlo, Alessandra;Tieghi, Alessia;Heidel, Florian H;Caocci, Giovanni;Beggiato, Eloise;Binotto, Gianni;Cavazzini, Francesco;Miglino, Maurizio;Bosi, Costanza;Crugnola, Monica;Bocchia, Monica;Martino, Bruno;Pugliese, Novella;Biondo, Mattia;Venturi, Marta;Scaffidi, Luigi;Isidori, Alessandro;Cattaneo, Daniele;Krampera, Mauro;Pane, Fabrizio;Cilloni, Daniela;Semenzato, Gianpietro;Lemoli, Roberto M;Cuneo, Antonio;Abruzzese, Elisabetta;Bartoletti, Daniela;Paglia, Simona;Vianelli, Nicola;Cavo, Michele;Bonifacio, Massimiliano;Palumbo, Giuseppe A

2023-01-01

---

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.