Second primary malignancy in myelofibrosis patients treated with ruxolitinib

Nicola Polverelli, Elena M. Elli, Elisabetta Abruzzese, Giuseppe A. Palumbo, Giulia Benevolo, Mario Tiribelli, Massimiliano Bonifacio, Alessia Tieghi, Giovanni Caocci, Mariella D'Adda, Micaela Bergamaschi, Gianni Binotto, Florian H. Heidel, Francesco Cavazzini, Monica Crugnola, Novella Pugliese, Costanza Bosi, Alessandro Isidori, Daniela Bartoletti, Giuseppe AuteriRoberto Latagliata, Lisa Gandolfi, Bruno Martino, Luigi Scaffidi, Daniele Cattaneo, Fabio D’Amore, Malgorzata M. Trawinska, Rossella Stella, Uros Markovic, Lucia Catani, Fabrizio Pane, Antonio Cuneo, Mauro Krampera, Gianpietro Semenzato, Roberto M. Lemoli, Nicola Vianelli, Massimo Breccia, Domenico Russo, Michele Cavo, Alessandra Iurlo, Francesca Palandri

Research output: Contribution to journalArticlepeer-review

Abstract

Ruxolitinib (RUX), the first JAK1/JAK2 inhibitor approved for myelofibrosis (MF) therapy, has recently been associated with the occurrence of second primary malignancies (SPMs), mainly lymphomas and non-melanoma skin cancers (NMSCs). We analyzed the incidence, risk factors and outcome of SPMs in 700 MF patients treated with RUX in a real-world context. Median follow-up from starting RUX was 2·9 years. Overall, 80 (11·4%) patients developed 87 SPMs after RUX start. NMSCs were the most common SPMs (50·6% of the cases). Multivariate analysis demonstrated that male sex [hazard ratio (HR): 2·37, 95% confidence interval (95%CI): 1·22–4·60, P = 0·01] and thrombocytosis> 400 × 109/l at RUX start (HR:1·98, 95%CI: 1·10–4·60, P = 0·02) were associated with increased risk for SPMs. Risk factors for NMSC alone were male sex (HR: 3·14, 95%CI: 1·24–7·92, P = 0·02) and duration of hydroxycarbamide and RUX therapy > 5 years (HR: 3·20, 95%CI: 1·17–8·75, P = 0·02 and HR: 2·93, 95%CI: 1·39–6·17, P = 0·005 respectively). In SPMs excluding NMSCs, male sex (HR: 2·41, 95%CI: 1·11–5·25, P = 0·03), platelet > 400 × 109/l (HR: 3·30, 95%CI: 1·67–6·50, P = 0·001) and previous arterial thromboses (HR: 3·47, 95%CI: 1·48–8·14, P = 0·004) were shown to be associated with higher risk of SPMs. While it is reassuring that no aggressive lymphoma was documented, active skin surveillance is recommended in all patients and particularly after prolonged hydroxycaramide therapy; oncological screening should be triggered by thrombocytosis and arterial thrombosis, particularly in males.

Original languageEnglish
JournalBritish Journal of Haematology
DOIs
Publication statusAccepted/In press - 2020

Keywords

  • JAK inhibitors
  • myelofibrosis
  • ruxolitinib
  • second cancer
  • toxicity

ASJC Scopus subject areas

  • Hematology

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