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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

1
Knight Cancer Institute, Oregon Health & Science University, Portland, OR.
2
Division of Hematology, Department of Medicine, Stanford University School of Medicine/Stanford Cancer Institute, Stanford, CA.
3
University of Utah, Huntsman Cancer Institute, Salt Lake City, UT.
4
Division of Hematology, Department of Medicine, Washington University in St Louis, St Louis, MO.
5
Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX.
6
Hematology/Oncology, The University of Texas Southwestern Medical Center, Dallas, TX.
7
Winship Cancer Institute, Emory University, Atlanta, GA.
8
Department of Pathology, Oregon Health & Science University, Portland, OR.
9
Howard Hughes Medical Institute, Chase, MD.

Abstract

PURPOSE:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

PMID:
31880950
DOI:
10.1200/JCO.19.00895

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