Evidence supports the use of ruxolitinib in patients with chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML), according to an oral presentation delivered at the 60th ASH Annual Meeting & Exposition
in San Diego, California.
Currently, there are no effective therapies for these 2 rare myeloid malignancies, which have an estimated median survival of 2 years.
In order to evaluate the safety and efficacy of ruxolitinib, a team of investigators enrolled 20 CNL and 20 aCML patients in a phase 2 study. After undergoing a 7-day washout period designed to reduce white blood cell counts, the patients received a daily starting dose of 20 mg, and during the study period the dose was 30 mg administered twice daily.
Half of the patients were positive for CSF3R-T618I mutation, the signature mutation in CNL and aCML cases. The patients’ average age was 73.2 years, and there were 17 females and 23 males included in the study. The patients completed an average of 7 cycles, which were 28 days long.
Ruxolitinib is an oral, small molecule JAK1/2 inhibitor from Incyte Corporation, Kim-Hien Dao, DO, PhD told Rare Disease Report
The overall response rate was 37%, with 11 patients achieving partial response and 2 achieving complete response. In the patients who did not achieve a complete response, but did achieve a partial response or disease stability, the authors noted that there was still clinical benefit in terms of hemoglobin improvement, platelet count improvement, symptom burden reduction, and spleen volume reduction.
“Not only did we observe some of the clinical benefits we were expecting, we also observed that some patients experienced complete responses with significant reduction in allele burden, a measure of the number of leukemia cells remaining,” Dr. Dao said. “In these cases, we noted that the oncogenic driver mutation in colony stimulating factor-3 receptor (CSF3R) gene, a mutation that results in uncontrolled, cancerous growth in some patients with CNL and aCML, became undetectable or nearly undetectable.”
The researchers said they found 1 adverse event that was related to ruxolitinib: nutritional weight gain in 1 case. Other adverse events included bleeding, infection, and death, which were not considered related to the drug. Disease progression was the most common cause of death, resulting in 11 deaths.
“Upon a closer look at the patients that achieved a very good clinical response to ruxolitinib, we learned that the 2 best responses occurred in patients with a CSF3R mutation in isolation with no other disease-modifying mutations that we consider detrimental in other types of leukemia,” Dr. Dao added. “These findings suggest that patients who have early disease characteristics are more likely to gain significant benefit from ruxolitinib and potentially achieve complete response at a deeper level. This implies that early detection, and therefore early intervention, may be important in these rare types of leukemia.”
Patients who remained on treatment for their ongoing benefit were allowed to enroll in an extension phase after 24 cycles of ruxolitinib treatment.
The abstract, titled “Phase 2 Study of Ruxolitinib in Patients with Chronic Neutrophilic Leukemia or Atypical Chronic Myeloid Leukemia,” was published online