Ruxolitinib/Navitoclax Shows Efficacy in Relapsed/Refractory Myelofibrosis

Naveen Pemmaraju, MD, associate professor in the Department of Leukemia, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discusses the results of combining ruxolitinib (Jakafi) and navitoclax in different high-risk populations of relapsed/refractory myelofibrosis.

In the ongoing phase 2 study (NCT03222609)of ruxolitinib plus navitoclax, over 30 patients who had a suboptimal response to ruxolitinib alone in myelofibrosis have been treated so far. Pemmaraju says the novel findings he presented at the 2020 American Society of Hematology (ASH) Annual Meeting are in the setting of high-risk molecular mutations and cytokine profiling that was built into the trial from the beginning.

For patients with high-risk molecular mutations, it was notable that about half the patients had 2 or more high-risk mutations. The addition of the navitoclax demonstrated clinical benefit for most of these patients. Pemmaraju thinks it is nice to know that even in the presence of high-risk mutations, this combination regimen is still providing clinical benefit.

Other findings from this trial come from an evaluation of patients’ cytokines. Patients with myelofibrosis have an upregulation of these cytokines. These data showed that several of the cytokines were elevated. The new interesting data are that there were a couple of new cytokines that we found that were upregulated in the setting of myelofibrosis and may be modulated by the combination, according to Pemmaraju. He thinks these new cytokines need to be further investigated in this ongoing study as well as other studies, and it will be important to see what the significance is.