Send to

Choose Destination
J Clin Oncol. 2019 Dec 27:JCO1900895. doi: 10.1200/JCO.19.00895. [Epub ahead of print]

Efficacy of Ruxolitinib in Patients With Chronic Neutrophilic Leukemia and Atypical Chronic Myeloid Leukemia.

Author information

Knight Cancer Institute, Oregon Health & Science University, Portland, OR.
Division of Hematology, Department of Medicine, Stanford University School of Medicine/Stanford Cancer Institute, Stanford, CA.
University of Utah, Huntsman Cancer Institute, Salt Lake City, UT.
Division of Hematology, Department of Medicine, Washington University in St Louis, St Louis, MO.
Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX.
Hematology/Oncology, The University of Texas Southwestern Medical Center, Dallas, TX.
Winship Cancer Institute, Emory University, Atlanta, GA.
Department of Pathology, Oregon Health & Science University, Portland, OR.
Howard Hughes Medical Institute, Chase, MD.



Colony-stimulating factor-3 receptor (CSF3R)-T618I is a recurrent activating mutation in chronic neutrophilic leukemia (CNL) and to a lesser extent in atypical chronic myeloid leukemia (aCML) resulting in constitutive JAK-STAT signaling. We sought to evaluate safety and efficacy of the JAK1/2 inhibitor ruxolitinib in patients with CNL and aCML, irrespective of CSF3R mutation status.


We conducted a phase II study of ruxolitinib in 44 patients (21 CNL and 23 aCML). The primary end point was overall hematologic response rate (ORR) by the end of 6 continuous 28-day cycles for the first 25 patients enrolled. We considered a response as either partial (PR) or complete response (CR). We expanded accrual to 44 patients to increase our ability to evaluate secondary end points, including grade ≥ 3 adverse events, spleen volume, symptom assessment, genetic correlates of response, and 2-year survival.


ORR was 32% for the first 25 enrolled patients (8 PR [7 CNL and 1 aCML]). In the larger cohort of 44 patients, 35% had a response (11 PR [9 CNL and 2 aCML] and 4 CR [CNL]), and 50% had oncogenic CSF3R mutations. The mean absolute allele burden reduction of CSF3R-T618I after 6 cycles was greatest in the CR group, compared with the PR and no response groups. The most common cause of death is due to disease progression. Grade ≥ 3 anemia and thrombocytopenia were observed in 34% and 14% of patients, respectively. No serious adverse events attributed to ruxolitinib were observed.


Ruxolitinib was well tolerated and demonstrated an estimated response rate of 32%. Patients with a diagnosis of CNL and/or harboring CSF3R-T618I were most likely to respond.


Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center