Expert Hopeful to Add Novel Agents to MPN Armamentarium

Vivian G. Oehler, MD

Several advancements have been made in the treatment of patients with myeloproliferative neoplasms (MPNs) in recent years, said Vivian G. Oehler, MD, but a number of emerging drugs as monotherapy and in combination are showing promise in clinical trials.

“I would say that we should all stay hopeful,” said Oehler. “There are several interesting drugs that are showing intriguing results in trials, whether it’s PRM-151, an antifibrotic agent, or other combinations based on molecular profiling that we see in myelofibrosis. We hope that we can bring new therapies into the clinic that will extend beyond clinical trials over the next few years.”

For example, results from the second stage of a phase II study, presented at the 2019 European Hematology Association Congress, showed that PRM-151 improved bone marrow fibrosis severity, transfusion dependence, as well as other symptoms in a cohort of patients with higher-risk myelofibrosis who had an inadequate response or were ineligible to receive ruxolitinib (Jakafi).¹ Results from the first stage of the trial showed that when PRM-151 was administered in combination with ruxolitinib, the treatment decreased bone marrow fibrosis and improved hemoglobin and platelet levels in those who received it.

Ruxolitinib, however, has served as an integral aspect of care for those with myelofibrosis and polycythemia vera (PV). The JAK1/2 inhibitor received approval from the FDA in 2011 for the treatment of patients with intermediate- and high-risk myelofibrosis, and in 2014 was also approved for use in patients with PV who were intolerant or resistant to hydroxyurea.

Another agent that has been used in the PV treatment paradigm is interferon. In the phase III PROUD-PV trial, investigators compared ropeginterferon alfa-2b (PEG-Intron) with hydroxyurea in patients with PV. After 1 year, patients were rolled over to the CONTI-PV trial, with the option to switch from hydroxyurea to best available therapy (BAT).

Results showed that after 3 years of treatment, maintenance of higher response rates was shown in patients who received ropeginterferon alfa-2b compared with those who received hydroxyurea/BAT for complete hematologic response (CHR) and for CHR plus symptom improvement.² Furthermore, over the course of 2 years, response rates were observed to have steadily increased in those who were given ropeginterferon alfa-2b compared with those who received hydroxyurea/BAT; this trend remained constant after 36 months.

In an interview with OncLive^® during the 2019 State of the Science Summit™ on Hematologic Malignancies, Oehler, associate member, Fred Hutchinson Cancer Research Center, associate professor of medicine, Division of Hematology, University of Washington School of Medicine, and hematologic oncologist, Seattle Cancer Care Alliance, highlighted ongoing developments in MPNs and shared her hopes for the future.

OncLive: What are some of the key updates that are important to highlight in MPNs?

Oehler: For MPNs, I spoke a little bit about the ongoing different data that we've had with regard to using interferon in PV. I'm also going to discuss some of the new ways that we've used molecular data to improve risk stratification for patients with myelofibrosis, and then there have been several clinical trials and a number of ongoing new trials with very interesting mechanisms. I provided a snapshot of where we stand in 2019 with some of these studies and what directions we might be going in the next 1 to 2 years.

What is the role of interferon in the paradigm?

Interferon is certainly an excellent therapy that we have used in PV for a number of years; it's mechanism of action still remains a little bit unclear; [specifically, we don’t know] whether it could potentially target an MPN stem cell.

The PROUD-PV and its continuation study did show some interesting data in abstract format. [With that study it appeared that], over time, CHRs were increasing in years 2 and 3 and that perhaps there was a decrease in the burden of JAK2 at the molecular level. However, we know from the studies here in the United States, such as the MPD-RC 112 study, that they looked pretty much the same and that there wasn't an improvement and perhaps there were increased adverse events in patients who received pegylated interferon. However, I do believe it's a therapy that can be considered for patients and a better understanding of its mechanism of action will help us in deciding who to treat with this agent.

References

1. Verstovsek S, Talpaz M, Wadleigh M, et al. A randomized, double blind phase 2 study of 3 different doses of PRM-151 in patients with myelofibrosis who were previously treated with or ineligible for ruxolitinib. Presented at: 2019 European Hematology Association Annual Congress; June 13-16, 2019; Amsterdam, The Netherlands. Abstract S828.
2. Gisslinger H, Klade C, Georgiev P, et al. Evidence for superior efficacy and disease modification after three years of prospective randomized controlled treatment of polycythemia vera patients with ropeginterferon alfa-2b vs. HU/BAT. Blood. 2018;132:579. doi: 10.1182/blood-2018-99-118715.