A Phase I/II Study of the Janus Kinase (JAK)1 and 2 Inhibitor Ruxolitinib in Patients With Relapsed or Refractory Acute Myeloid Leukemia

作者：Pemmaraju Naveen; Kantarjian Hagop; Kadia Tapan; Cortes Jorge; Borthakur Gautam; Newberry Kate; Garcia Manero Guillermo; Ravandi Farhad; Jabbour Elias; Del****la Sara; Pierce Sherry; Verstovsek Srdan^*

来源：Clinical Lymphoma Myeloma & Leukemia, 2015, 15(3): 171-176.

DOI：10.1016/j.clml.2014.08.003

• Acute myelogenous leukemia
• Clinical study
• JAK2V617 mutation
• Janus kinase inhibitor
• Myelofibrosis
• Ruxolitinib

Ruxolitinib is a potent and specific Janus kinase (JAK)1/JAK2 inhibitor recently approved for the treatment of myelofibrosis. We enrolled 27 patients older than 14 years with relapsed or refractory acute myeloid leukemia (n = 26) or acute lymphoid leukemia (n = 1). One patient with multiple relapses after 7 lines of therapy achieved a complete remission with incomplete recovery of peripheral blood counts (CRp) at a ruxolitinib dose of 200 mg twice per day (bid.).
Background: Ruxolitinib is a potent and specific JAK1/JAK2 inhibitor recently approved for the treatment of myelofibrosis. Patients and Methods: We conducted a single-center phase I/II clinical study testing 3 dose levels (50 mg b.i.d. [n = 4], 100 mg b.i.d. [n = 5], and 200 mg b.i.d. [n = 18]). We enrolled 27 patients older than 14 years with relapsed or refractory acute myeloid leukemia (n = 26) or acute lymphoid leukemia (n = 1). Results: The median age was 66 (range, 25-88) years. Thirteen patients were evaluable for dose-limiting toxicities. The most common Grade 3 or 4 nonhematologic event was infection (n = 26 events; most frequently pneumonia; 15 of 26; 58%). One patient with multiple relapses after 7 lines of therapy had a CRp at a ruxolitinib dose of 200 mg b.i.d. Conclusion: In this cohort of heavily pretreated patients with relapsed or refractory acute leukemias, ruxolitinib was overall reasonably well tolerated, with 1 patient achieving CRp.

• 出版日期2015-3