Micrograph showing MF

Results of the SIMPLIFY-1 study revealed how 2 JAK inhibitors—momelotinib and ruxolitinib—compared to one another in myelofibrosis (MF) patients who were previously JAK-inhibitor-naïve.

Momelotinib proved noninferior to ruxolitinib when it came to spleen reduction but not symptom response.

On the other hand, momelotinib was more effective than ruxolitinib in reducing transfusion dependence.

The overall incidence of adverse events (AEs) was similar between the treatment arms.

However, patients receiving momelotinib were more likely to experience AEs leading to treatment discontinuation.

Ruben A. Mesa, MD, of Mayo Clinic Cancer Center in Phoenix, Arizona, and his colleagues reported these results in the Journal of Clinical Oncology. The study was sponsored by Gilead Sciences.

SIMPLIFY-1 was a phase 3, double-blind, active-controlled study. It enrolled 432 patients with symptomatic intermediate-1-risk MF, intermediate-2-risk MF, or high-risk MF.

These JAK-inhibitor-naïve patients were randomized to receive 24 weeks of treatment with momelotinib (n=215, 200 mg once daily) or ruxolitinib (n=217, 20 mg twice a day or per label). After that, all patients could receive open-label momelotinib.

The researchers said baseline characteristics were similar between the treatment arms. In the overall cohort, most patients were white (82.6%), male (56.5%), 65 or older (57.2%), and had primary MF (56.5%).

In all, 376 patients completed 24 weeks of treatment—175 in the momelotinib arm and 201 in the ruxolitinib arm. And 368 patients proceeded to the open-label phase of the study—171 from the momelotinib arm and 197 from the ruxolitinib arm (who switched to momelotinib).

Efficacy

The primary efficacy endpoint was spleen response rate at 24 weeks, which was defined as the proportion of patients achieving at least a 35% reduction in spleen volume.

This endpoint was achieved by a similar proportion of patients in both treatment arms—26.5% in the momelotinib arm and 29% in the ruxolitinib arm. This met the criteria for noninferiority (P=0.011).

On the other hand, noninferiority was not met for total symptom score, which was the proportion of patients achieving at least a 50% reduction in MF symptoms. This endpoint was achieved by 28.4% in the momelotinib arm and 42.2% in the ruxolitinib arm (P=0.98 for noninferiority).

A greater proportion of patients were transfusion-independent at week 24 in the momelotinib arm than the ruxolitinib arm—66.5% and 49.3%, respectively (nominal P<0.001).

The median rate of red blood cell transfusion was 0 units per month in the momelotinib arm and 0.4 units per month in the ruxolitinib arm (nominal P<0.001).

Safety

Most patients had at least 1 AE—92.1% in the momelotinib arm and 95.4% in the ruxolitinib arm. Grade 3 or higher AEs occurred in 35.5% and 43.5%, respectively.

Serious AEs occurred in 22.9% and 18.1%, respectively. AEs leading to treatment discontinuation occurred in 13.1% and 5.6%, respectively.

Treatment-emergent AEs occurring in at least 10% of patients in either treatment arm (momelotinib and ruxolitinib, respectively) were thrombocytopenia (18.7% and 29.2%), diarrhea (17.8% and 19.9%), headache (17.3% and 19.9%), dizziness (15.9% and 11.6%), nausea (15.9% and 3.7%), fatigue (14.5% and 12.0%), anemia (13.6% and 38%), abdominal pain (10.3% and 11.1%), and peripheral neuropathy (10.3% and 4.6%).

The most common grade 3/4 AEs in the momelotinib arm were thrombocytopenia (7.0%), anemia (5.6%), diarrhea (2.8%), hypertension (2.8%), and neutropenia (2.8%).

The most common grade 3/4 AEs in the ruxolitinib arm were anemia (23.1%), neutropenia (4.6%), thrombocytopenia (4.6%), and hypertension (4.2%).

There were 7 deaths in the momelotinib arm. The causes of death were listed as enteritis, mesenteric vein thrombosis, death, sudden death, sepsis, renal failure, and aortic dissection.

There were 7 deaths in the ruxolitinib arm as well. The causes of death were melena, sepsis, pneumonia, head injury, acute myeloid leukemia, recurrent mantle cell lymphoma, and coma.

Transformation to acute myeloid leukemia occurred in 1 patient in the momelotinib arm (grade 4) and 2 patients in the ruxolitinib arm (grade 3 and grade 5).

JAK inhibitors face off in myelofibrosis trial