Molotinib Update: Molotinib Improves Anemia in Myelofibrosis Patients Not Taking JAK Inhibitors

Treatment with molotinib (Ojjaara) is beneficial for anemia in myelofibrosis patients who were naïve to JAK inhibitors, regardless of baseline hemoglobin levels. Additionally, molotinib had a significant anemia benefit compared with ruxoltinib (Jakafi), according to an analysis of the phase 3 SIMPLIFY-1 study (NCT01969838).

SIMPLIFY-3 randomized 432 patients with myelofibrosis who were not receiving JAK inhibitors to receive molotinib or ruxolitinib. In patients with anemia who received molotinib, mean hemoglobin levels increased between weeks 2 and 4 of treatment, whereas hemoglobin levels remained stable in anemic patients who did not receive a JAK inhibitor.

In contrast, mean hemoglobin initially decreased in anemic and non-anemic patients treated with ruxolitinib. This decrease stabilized after weeks 4 to 6 as patients received red blood cell transfusions. Patients receiving ruxolitinib were allowed to cross over to the molotinib arm, and mean hemoglobin levels increased after this change.

The study also evaluated patients with varying degrees of anemia. Among patients with mild anemia with hemoglobin levels between 10 and 12 g/dL, 90.4% were transfusion-free at baseline, and 93.9% of these patients remained transfusion-free while receiving momotinib. Four patients who were not transfused at baseline became transfused during treatment. In contrast, mildly anemic patients in the ruxolitinib group became more transfusion dependent; 50% of patients who were not transfused at baseline required a transfusion while taking ruxolitinib.

Although treatment of mild anemia (hemoglobin level≥10 to <12 g/dL) is not always routinely considered, our analysis also highlights the potential value of molotinib in maintaining transfusion independence in eligible patients with mild anemia who require JAK inhibitor therapy.

For patients who were not anemic, all patients in the molotinib group were transfusion-free at baseline and remained so. Five patients in the ruxolitinib group who were not transfused at baseline required transfusions during treatment.

Although molotinib has shown benefit in anemic subgroups, the effect of molotinib in non-anemic patients is unclear. Among patients with moderate or severe anemia, 34.1% of patients in the morotinib group were transfusion-free at baseline. Fourteen of the patients who required transfusions at baseline were able to become transfusion-free, whereas 86.2% of patients who were not transfused at baseline remained so. In the ruxolitinibgroup, only 30% of patients with moderate or severe anemia who had not received transfusions at baseline remained so.

No new safety signals were identified for molotinib. Discontinuation due to adverse events was more common among people with moderate to severe anemia treated with morotinib (18.8%) compared with ruxolitinib (6.3%). However, dose reductions or interruptions were more common with ruxolitinib than with molotinib ( 36.8% vs. 21.2%, respectively).

The clinical benefit and safety profile of molotinib in JAK inhibitor-naïve myelofibrosis patients in mild-to-severe anemic and non-anemic subgroups were generally consistent with that observed in the overall SIMPLIFY-1 trial population, making it a potential treatment option for patients with myelofibrosis regardless of baseline hemoglobin levels.