Ruxolitinib: The First FDA Approved Therapy for the Treatment of Myelofibrosis Full Text
Clinical Cancer Research, 04/03/2012
Mascarenhas J et al. – Ruxolitinib offers a well–tolerated oral therapeutic option for MF patients with symptomatic splenomegaly and debilitating disease related symptoms, but does not appear effective in eliminating the underlying hematological malignancy.
- The BCR-ABL1-negative myeloproliferative neoplasms (essential thrombocythemia, polycythemia vera, and primary myelofibrosis) are a group of heterogeneous hematologic malignancies involving a clonal proliferation of hematopoietic stem cells.
- Thrombosis, bleeding and transformation to acute leukemia reduce the overall survival of patients with myelofibrosis, a disease typified by progressive splenomegaly and disease related symptoms such as fatigue, pruritus, and bony pains.
- Hematopoietic stem cell transplant offers the only potential for cure in a minority of eligible patients, leaving a serious unmet need for improved therapies.
- Recent advances in the understanding of the pathogenetic mechanisms underlying these diseases has led to an explosion of clinical trials evaluating novel therapies.
- The discovery of an activating mutation in the Janus associated kinase 2 (JAK2) gene provided a therapeutic target to down-regulate this activated signaling pathway influencing the phenotype of these diseases.
- Ruxolitinib (Jakafi, Incyte) is a small molecule inhibitor of JAK1/2 that has proven to be effective in reducing splenomegaly and ameliorating symptoms in myeloproliferative neoplasms.
- Based on the results of two pivotal randomized phase III clinical trials, Ruxolitinib has become the first FDA approved therapeutic for the treatment of patients with myelofibrosis.