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Recent advances in JAK2 inhibition for the treatment of myelofibrosis.
Rippel, Noa; Kremyanskaya, Marina.
Afiliação
  • Rippel N; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Kremyanskaya M; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Expert Opin Pharmacother ; 25(9): 1175-1186, 2024 Jun.
Article em En | MEDLINE | ID: mdl-38919983
ABSTRACT

INTRODUCTION:

Myelofibrosis (MF) is a BCR-ABL-negative myeloproliferative neoplasm characterized by splenomegaly, constitutional symptoms, cytopenias, a potential for leukemic transformation, and increased mortality. Patients who are ineligible for stem cell transplant rely on pharmacologic therapies of noncurative intent, whose cornerstone consists of JAK inhibitors (JAKi). While current JAKi are efficacious in controlling symptoms and splenic volume, none meaningfully reduce clonal burden nor halt disease progression, and patients oftentimes develop JAKi intolerant, relapsed, or refractory MF. As such, there remains an urgent necessity for second-line options and novel therapies with disease-modifying properties. AREAS COVERED In this review, we delineate the mechanistic rationale, along with the latest safety and efficacy data, of investigational JAKi-based MF treatment strategies, with a focus on JAKi monotherapies and combinations of novel agents with approved JAKi. Our literature search consisted of extensive review of PubMed and clinicaltrials.gov. EXPERT OPINION A myriad of promising MF-directed therapies are in late-phase studies. Following their approval, treatment selection should be tailored to patient-specific treatment goals and disease characteristics, with an emphasis on combination therapies of JAKi with novel agents of differing mechanistic targets that possess anti-clonal properties, in attempt to alter disease course and concurrently limit dose-dependent JAKi toxicities.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Janus Quinase 2 / Mielofibrose Primária / Inibidores de Janus Quinases Idioma: En Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Janus Quinase 2 / Mielofibrose Primária / Inibidores de Janus Quinases Idioma: En Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos