Dr. Kuykendall on the Investigation of Navitoclax Plus Ruxolitinib in Myelofibrosis

Andrew Kuykendall, MD, assistant member, the Department of Malignant Hematology, Moffitt Cancer Center, discusses the investigation of navitoclax (ABT-263) plus ruxolitinib (Jakafi) in myelofibrosis.

The phase 2 REFINE trial (NCT03222609) evaluated the tolerability and efficacy of navitoclax alone or in combination with ruxolitinib in patients with myelofibrosis.

Navitoclax is a BCL-2/BCL-XL inhibitor, and although there is excitement surrounding BCL-2 inhibitors, BCL-XL inhibitors may be more relevant within the settings of myelofibrosis and myeloproliferative neoplasms, Kuykendall says.

Navitoclax was investigated both as a single agent and in combination with ruxolitinib in multiple cohorts in the REFINE trial, with patients enrolled based on prior experience with JAK inhibition. Navitoclax was added onto ruxolitinib in patients who were suboptimal responders the JAK inhibition alone, and navitoclax monotherapy and in combination with ruxolitinib was evaluated in the frontline setting as a single agent, Kuykendall adds.

Initial data from REFINE trial were from add-on setting, where patients who had previous suboptimal responses to ruxolitinib alone received the combination therapy. Data showed that 27% of these patients achieved a spleen volume reduction of at least 35% (n = 9/34), 30% of patients had a total symptom score (TSS) reduction of at least 50% (n = 6/20), and 21% of patients had bone marrow improvement (n = 7/34). These data were intriguing, particularly regarding some high-risk molecular subgroups, Kuykendall emphasizes.

More data have started to emerge for the use of navitoclax in the frontline setting. Preliminary findings have showed that the up-front combination of navitoclax plus ruxolitinib has generated responses, which is not surprising given ruxolitinib’s known ability to induce responses as a single agent in the frontline setting, Kuykendall continues.

As more up-front data are reported, investigators will aim to see if the addition of navitoclax to ruxolitinib can lead to deeper, more durable responses with the combination that could improve outcomes for patients with myelofibrosis, Kuykendall concludes.