By Catlin Nalley
With ongoing advancements, the therapeutic landscape for myeloproliferative neoplasms continues to evolve. Naveen Pemmaraju, MD, Associate Professor in the Department of Leukemia at the University of Texas MD Anderson Cancer Center, discussed where the field currently stands during his presentation, “Promising New Drugs for MPN Therapy,” at the International Congress on Myeloproliferative Neoplasms, held November 2-3, 2023, in New York.
When it comes to myeloproliferative neoplasms, “we have entered into a new golden era of research and potential that we have never seen before,” he noted. “Our field has been previously dominated by the first breakthrough—JAK inhibitor monotherapy—which was fantastic for our patients. However, as much of a revolution as this era was, by and large, it did not lead to cures of the disease. The only curative therapy as we close 2023 remains allogeneic stem cell transplant.”
In recent years, the field has seen breakthroughs with novel agents beyond the JAK/STAT pathway, according to Pemmaraju, who also highlighted the growing exploration of combination therapies in this patient population. “This is an important time in the MPN field,” he emphasized. “All of this is coming together, hopefully for the immediate good of our patients and then also establishing a new scientific era in myeloproliferative neoplasms,” he stated.
Main Takeaways
While discussing his presentation—and the MPN field as a whole—with Oncology Times, Pemmaraju highlighted a research study that explored life after ruxolitinib in myelofibrosis patients (Cancer 2020; doi: 10.1002/cncr.32664). Interestingly, he noted that the trial found that 40.8 percent of patients had stopped ruxolitinib at 3 years. Reasons for discontinuation included lack or loss of a spleen response, ruxolitinib-related adverse events, progression to blast phase, ruxolitinib-unrelated adverse events, and allogeneic transplantation during response.
The data also showed that the median survival after ruxolitinib was 13.2 months and the use of investigational agents was in fact associated with improved outcomes versus conventional agents, according to Pemmaraju, who noted this underscores the importance of ongoing investigation and advances.
In terms of combination treatments, Pemmaraju highlighted many different approaches, such as navitoclax, a BCL-XL/BCL-2 inhibitor. The potential of this agent has been explored in several studies, including the Phase II REFINE study (J Clin Oncol 2022; doi: 10.1200/JCO.21.02188). Data showed the addition of navitoclax to ruxolitinib among patients with persistent or progressive myelofibrosis led to durable spleen volume reduction, improved total symptom score, and hemoglobin response, reported Pemmaraju, an investigator on the trial.
Two phase III trials are currently underway to further explore the combination of navitoclax and ruxolitinib. The TRANSFORM-1 study is a frontline, upfront JAK inhibitor-naive study of ruxolitinib plus navitoclax versus ruxolitinib plus placebo. The other Phase III study, TRANSFORM-2, is looking at the efficacy and safety of this combination beyond the frontline setting.
Pemmaraju also highlighted several new novel agents that could have an impact on how we approach the treatment of MPNs. This includes but is not limited to agents that target the MDM2 pathway, telomerase inhibition, and cell cycle.
Additionally, he discussed another avenue targeting anemia in myelofibrosis. For instance, momelotinib was recently approved in September 2023 for intermediate or high-risk myelofibrosis, including primary myelofibrosis or secondary myelofibrosis (post-polycythemia vera and post-essential thrombocythemia), in adults with anemia. Luspatercept is another example. This agent recently gained FDA approval for the treatment of anemia in myelodysplastic syndrome and is currently being studied in patients with myelofibrosis.
As the field evolves and advancements continue, Pemmaraju emphasized what is most important—the patient. “Everything we do is for our patients and every stakeholder has an important role to play,” he said. “Let’s continue to have awesome discoveries in the lab. Let’s pledge together to try to translate those quickly with all of our stakeholders who can help bring these findings to the clinic.
“And then, let’s make a pledge together to disseminate those findings accurately, faithfully, and rapidly through all platforms, not just academic literature, so that everyone can see these data in real time, debate, discuss, and have a say,” Pemmaraju concluded.