The overall response rate is 37% (13 of 35 patients: 11 PR [8 CNL and 3 aCML] and 2 CR [2 CNL]). Response rate by mutation status is 50% (10 of 20) in the CSF3R-T618I group...Ruxolitinib provides clinical benefit in at least a third of CNL and aCML patients and is well-tolerated in this patient population. The greatest clinical benefit was among those with CSF3R-T618I mutation.

...a 75 year old man who was diagnosed with CSF3R-T618I...Eventually, he was treated with ruxolitinib, an FDA-approved JAK1/2 inhibitor, which resulted in dramatic improvement of his blood counts. He also had significant reduction of spleen volume and constitutional symptoms. This case highlights the need for a clinical trial to interrogate JAK1/2 as a potential molecular target in CNL and aCML in patients with or without CSF3R mutation.

Patient 9, who had CNL with a CSF3R T618I mutation...Treatment of this patient with oral ruxolitinib (at a dose of 10 mg twice daily) resulted in a marked decrease in the total number of white cells and the absolute neutrophil count. Increasing the dose of ruxolitinib to 15 mg twice daily led to a further decrease in both the white-cell count and the absolute neutrophil count. This treatment also resulted in normalization of the platelet count.

Mice transplanted with CSF3R T618I–expressing hematopoietic cells developed a myeloproliferative disorder characterized by overproduction of granulocytes and granulocytic infiltration of the spleen and liver, which was uniformly fatal. Treatment with the JAK1/2 inhibitor ruxolitinib lowered the white blood count and reduced spleen weight. This demonstrates that activating mutations in CSF3R are sufficient to drive a myeloproliferative disorder resembling a CML and CNL that is sensitive to pharmacologic JAK inhibition.