Dr. Garcia on Unmet Need in Myelofibrosis

Jacqueline S. Garcia, MD, instructor in medicine, Department of Medical Oncology, Harvard Medical School, and physician, Dana-Farber Cancer Institute, discusses unmet needs for patients with myelofibrosis who progress on JAK inhibitors.

Currently, there are no approved treatments for patients who progress on ruxolitinib (Jakafi) or fedratinib (Inrebic), says Garcia. Often patients who develop resistance to JAK inhibitors will experience disease progression.

Findings from a phase II study demonstrated a clinically meaningful reduction in spleen volume and improvement in symptoms with the addition of the BCL-2/BCL-XL inhibitor navitoclax to ruxolitinib in patients with primary or secondary myelofibrosis with acquired resistance to ruxolitinib.

Eligible patients had to have received a minimum of 12 weeks of continuous ruxolitinib. Additionally, patients had to have been on a stable dose of ruxolitinib of at least 10 mg twice daily for 8 weeks. By doing this, investigators could establish the toxicity profile of ruxolitinib alone and ensure patients derived the best response on ruxolitinib before coming onto study, says Garcia.

Patients received a starting dose of 50 mg of navitoclax and ≥10 mg of ruxolitinib twice daily. After weekly assessments, the dose of navitoclax was escalated to 300 mg daily based on tolerability and platelet counts.

The primary endpoint of the study was splenic volume reduction from baseline. Secondary endpoints included total symptom score benefit, overall response rate, rate of anemia response, improvement in bone marrow fibrosis, and safety, concludes Garcia.