RESUMO
The search for novel targets in chronic myeloid leukaemia (CML) is ongoing, to improve treatment efficacy in refractory disease and increase eligibility for tyrosine kinase inhibitor (TKI) discontinuation. Increased frequency of Tregs and effector Tregs was evident at diagnosis, together with increased expression of T-cell exhaustion markers, including in regulatory T cells at diagnosis and in patients with refractory disease. Plasma analysis revealed significantly increased levels of cytokines including tumour necrosis factor (TNF)-a and interleukin (IL)-6 at diagnosis, in keeping with a pro-inflammatory state prior to treatment. We hence demonstrate T-cell exhaustion and a pro-inflammatory state at diagnosis in CML, likely secondary to leukaemia-associated antigenic overload associated with increased disease burden.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Leucemia Mieloide , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Fenótipo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Linfócitos T ReguladoresRESUMO
Despite widespread use of Pegylated forms of Inteferon in the management of Myeloproliferative Neoplasms (MPN), most clinicians have experience predominantly with peginterferon alfa-2a (Pegasys). Third generation pegylated IFNα, ropeginterferon alfa-2b (ropegIFN; Besremi), was recommended by the European Medicine Authority (EMA) for treatment of Polycythaemia Vera (PV) following a Phase III trial (PROUD-PV / CONTINUATION-PV). FDA approval for PV, regardless of treatment history, was subsequently granted in November 2021. We hereby demonstrate the safety and tolerability of ropegIFN in a series of MPN patients at variable doses. It corroborates reports of efficacy of ropegIFN in patients with PV and use in pregnancy.
RESUMO
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