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

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

Cancer 2023 March 19

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.