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Ruxolitinib-based combinations in the treatment of myelofibrosis: worth looking forward to.

ABSTRACT: Ruxolitinib is a targeted drug to treat myelofibrosis (MF). Ruxolitinib has significant advantages in spleen reduction and increasing 5-year overall survival (OS), and ruxolitinib-based combinations might provide more benefits than ruxolitinib monotherapy. In this review, we focus on the data of ruxolitinib-based combinations therapies and treatment-related adverse events (AEs) and safety. We analyzed and summarized the data of ruxolitinib-based combinations. Ruxolitinib combined with prednisone + thalidomide + danazol (TPD), panobinostat, pracinostat, azacytidine, or hydroxyurea has well reduced spleen. Ruxolitinib combined with danazol or TPD had well therapies in improvement of hemoglobin (Hgb) and platelets (PLT). Most ruxolitinib-based combinations therapies showed a superior benefit on reduced treatment-related AEs than ruxolitinib monotherapy. Treatment-related AEs and dose modification affect the safety and tolerability of ruxolitinib-based combinations. Genetic testing before treatment is recommended. To provide better clinical guidance, comparisons of these randomized controlled trials with the trials of ruxolitinib alone are necessary. This review suggests that the clinical application of ruxolitinib-based combinations is worth waiting for.

SUBMITTER: Li Y

PROVIDER: S-EPMC7237512 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Ruxolitinib-based combinations in the treatment of myelofibrosis: worth looking forward to.

Li Yujin Y Zhu Shirong S Liu Weiyi W Ming Jing J Wang Xueying X Hu Xiaomei X

Annals of hematology 20200424 6

Ruxolitinib is a targeted drug to treat myelofibrosis (MF). Ruxolitinib has significant advantages in spleen reduction and increasing 5-year overall survival (OS), and ruxolitinib-based combinations might provide more benefits than ruxolitinib monotherapy. In this review, we focus on the data of ruxolitinib-based combinations therapies and treatment-related adverse events (AEs) and safety. We analyzed and summarized the data of ruxolitinib-based combinations. Ruxolitinib combined with prednisone ...[more]

PMID: 32333155

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Project description:Myelofibrosis is a BCR-ABL1-negative myeloproliferative neoplasm characterized by anemia, progressive splenomegaly, extramedullary hematopoiesis, bone marrow fibrosis, constitutional symptoms, leukemic progression, and shortened survival. Constitutive activation of the Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathway, and other cellular pathways downstream, leads to myeloproliferation, proinflammatory cytokine expression, and bone marrow remodeling. Transplant is the only curative option for myelofibrosis, but high rates of morbidity and mortality limit eligibility. Several prognostic models have been developed to facilitate treatment decisions. Until the recent approval of fedratinib, a JAK2 inhibitor, ruxolitinib was the only available JAK inhibitor for treatment of intermediate- or high-risk myelofibrosis. Ruxolitinib reduces splenomegaly to some degree in almost all treated patients; however, many patients cannot tolerate ruxolitinib due to dose-dependent drug-related cytopenias, and even patients with a good initial response often develop resistance to ruxolitinib after 2-3 years of therapy. Currently, there is no consensus definition of ruxolitinib failure. Until fedratinib approval, strategies to overcome ruxolitinib resistance or intolerance were mainly different approaches to continued ruxolitinib therapy, including dosing modifications and ruxolitinib rechallenge. Fedratinib and two other JAK2 inhibitors in later stages of clinical development, pacritinib and momelotinib, have been shown to induce clinical responses and improve symptoms in patients previously treated with ruxolitinib. Fedratinib induces robust spleen responses, and pacritinib and momelotinib may have preferential activity in patients with severe cytopenias. Reviewed here are strategies to ameliorate ruxolitinib resistance or intolerance, and outcomes of clinical trials in patients with myelofibrosis receiving second-line JAK inhibitors after ruxolitinib treatment.

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Ruxolitinib-based combinations in the treatment of myelofibrosis: worth looking forward to.

Publications

Ruxolitinib-based combinations in the treatment of myelofibrosis: worth looking forward to.

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