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. 2023 Jun 1;129(11):1704-1713.
doi: 10.1002/cncr.34722. Epub 2023 Mar 18.

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

Francesca Palandri  1 , Massimo Breccia  2 , Camilla Mazzoni  1   3 , Giuseppe Auteri  1   3 , Elena Maria Elli  4 , Malgorzata M Trawinska  5 , Nicola Polverelli  6 , Mario Tiribelli  7 , Giulia Benevolo  8 , Alessandra Iurlo  9 , Alessia Tieghi  10 , Florian H Heidel  11 , Giovanni Caocci  12 , Eloise Beggiato  8 , Gianni Binotto  13 , Francesco Cavazzini  14 , Maurizio Miglino  15   16 , Costanza Bosi  17 , Monica Crugnola  18 , Monica Bocchia  19 , Bruno Martino  20 , Novella Pugliese  21 , Mattia Biondo  1   3 , Marta Venturi  1   3 , Luigi Scaffidi  22 , Alessandro Isidori  23 , Daniele Cattaneo  9 , Mauro Krampera  22 , Fabrizio Pane  21 , Daniela Cilloni  24 , Gianpietro Semenzato  13 , Roberto M Lemoli  15   16 , Antonio Cuneo  14 , Elisabetta Abruzzese  25 , Daniela Bartoletti  1   3 , Simona Paglia  1 , Nicola Vianelli  1 , Michele Cavo  1   3 , Massimiliano Bonifacio  21 , Giuseppe A Palumbo  26
Affiliations
Free article

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

Francesca Palandri et al. Cancer. .
Free article

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.

Keywords: cytopenia; myelodepletive phenotype; myelofibrosis; myeloproliferative neoplasms; ruxolitinib.

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References

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