Dr. Yacoub on the Rationale For Parsaclisib After Suboptimal Response to Ruxolitinib in Myelofibrosis

Abdulraheem Yacoub, MD, an associate professor of medicine at the University of Kansas Medical Center, discusses the rationale behind examining parsaclisib following suboptimal response to ruxolitinib (Jakafi) in patients with myelofibrosis.

Ruxolitinib is an agent that has demonstrated notable activity in patients with myelofibrosis and has existed in the myeloproliferative neoplasm arsenal for several years, according to Yacoub. The agent has demonstrated splenic and clinical responses in this population; however, responses have not proven to be durable and it is rare that the responses are complete, Yacoub explains. The median time to loss of response is approximately 3 years with the agent, Yacoub says.

Some of the partial responses observed in patients who have been treated with ruxolitinib may be due, in part, to the PI3K delta pathway, which allows cancer cells to escape inhibition by JAK2 inhibitors, Yacoub explains. It was hypothesized that the combination of a JAK inhibitor and a PI3K inhibitor would provide a double hit to the pathway, yielding a deeper, more durable response, Yacoub concludes.