Dr. Garcia on the Role of Navitoclax in Myelofibrosis

Jacqueline S. Garcia, MD, instructor in Medicine, Department of Medical Oncology, Harvard Medical School, and physician, Dana-Farber Cancer Institute, discusses how navitoclax differs from other agents in primary or secondary myelofibrosis.

Navitoclax is an oral BH3 memetic that targets cells that are dependent on BCL-XL and not as dependent on BCL-2 and BCL-W, explains Garcia. This therapy shows that myelofibrosis cells undergo apoptotical priming, and there’s evidence for the activity of BCL-XL inhibition in reversing fibrosis and causing apoptosis, says Garcia.

In preclinical models, there has also been activity with BCL-XL inhibition and JAK2-mutant and -resistant models, according to Garcia. There is evidence of synergy when BCL-XL inhibitors and JAK2 inhibitors, such as ruxolitinib, are combined. Additionally, navitoclax as an oral therapy makes the combination interesting, concludes Garcia.