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Ruxolitinib for Rare BCR-ABL1–Negative Myeloid Neoplasms

By: Sarah Campen, PharmD
Posted: Tuesday, April 7, 2020

The JAK1/2 inhibitor ruxolitinib may prove to be an effective treatment option in some patients with chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (CML)—both rare BCR-ABL1–negative myeloid neoplasms—according to Kim-Hien T. Dao, DO, PhD, of the Knight Cancer Institute, Oregon Health & Science University, Portland, and colleagues. In a phase II study published in the Journal of Clinical Oncology, ruxolitinib was reported to be well tolerated and demonstrated a 35% response rate.

“Our study offers evidence supporting the clinical efficacy of ruxolitinib in one-third of patients with CNL and atypical CML and provides new insights on genetic features of CNL and atypical CML in the context of ruxolitinib therapy,” stated the authors.

Colony-stimulating factor-3 receptor (CSF3R)-T618I is a recurrent activating mutation in CNL and, to a lesser extent, in atypical CML. Ruxolitinib appears to target signaling downstream of oncogenic CSF3R.

In this study, the researchers enrolled 44 patients—21 with CNL and 23 with atypical CML— irrespective of their CSF3R mutation status. Partial responses were seen in nine patients with CNL and two patients with atypical CML, and complete responses were seen in four patients with CNL. Oncogenic CSF3R mutations were present in 50% of study patients. Complete responders had a larger reduction in allele burden of CSF3R-T618I after six cycles than partial responders and those who did not respond.

As for safety, 55% of patients experienced at least one grade ≥ 3 nonhematologic adverse event; the most common adverse events were fatigue, pneumonitis, and lung infection. Grade ≥ 3 hematologic events included anemia (34%) and thrombocytopenia (14%). The most common cause of death was disease progression (n = 13).

“Patients with a diagnosis of CNL and/or harboring CSF3R-T618I were most likely to respond to treatment with ruxolitinib,” concluded the authors.

Disclosure: For disclosures of the study authors, visit

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