New treatments target MPN disease progression

For 30 years, treatments for myeloproliferative neoplasms (MPNs) have focused on symptom relief and prevention of disease-related complications. However, with new medications being approved in recent years, the primary goals of treatment are starting to shift. Gabriela Hobbs, MD, clinical director of leukemia service at Massachusetts General Hospital, notes that treatment success is different for each patient and depends on the patient and the disease.

For a low-risk essential thrombocythemia (ET) patient without symptoms, success is living a normal quality of life without frequent doctor visits for labs and not getting overtreated. For patients with symptoms, success is improving those symptoms, such as resolving related anemia, which translates to needing fewer transfusions or feeling less tired.

Changing Treatment Goals

The goalposts for MPN treatment are moving, with a greater focus on disease modification and extending disease-free survival. Dr. Hobbs believes that with better targeted therapies, it’s possible to attack the disease where it starts and improve marrow morphology, which could reduce spleen size, improve symptoms, and improve blood counts.

Clinical trials are starting to reflect disease-modifying endpoints, with some studies looking at whether treatments reduce mutation load in the bone marrow. Dr. Hobbs is excited about new approaches being studied, including the use of PARP inhibitors and immunotherapies, which could significantly improve outcomes for patients with CALR mutations.

In the middle of this shift, it’s worth noting that the field of MPN treatment is not isolated, and advancements in other areas of oncology have also focused on moving beyond symptom relief. The push for more effective treatments in MPNs is part of a broader trend in cancer research, where the focus is increasingly on targeting the underlying causes of the disease rather than just managing its symptoms.

Joseph Scandura, MD, PhD, a physician scientist and MPN specialist at Weill Cornell Medicine, notes that the biology and therapies have advanced faster than trial endpoints, which still rely heavily on fixed, binary, short-term endpoints. He believes that the goal is to improve outcomes that patients care about, including longer life, delayed progression, and preserved quality of life.

The U.S. Food and Drug Administration (FDA) has recently approved new treatments for ET and polycythemia vera (PV), which is proof that the expanding toolkit for MPN treatment is already here. With more options available, patients have more choices for potential treatment success, and clinicians should appreciate this and be willing to switch to another medication if one isn’t controlling blood counts, improving symptoms, or anemia.

Treatment Takeaways

Today’s MPN patients have seen treatment options multiply across the MPN spectrum. Dr. Hobbs emphasizes that success is not just about managing symptoms but also about ensuring that patients are well-informed about their disease and treatment. With newer, better therapies available, patients should have higher expectations and discuss different options with their doctors.

An enlarged spleen remains a top complication for ET, PV, and myelofibrosis (MF) patients, causing uncomfortable physical symptoms and potentially leading to unintended weight loss. Treatment success may include resolving anemia, reducing spleen size, and improving blood counts, which can significantly impact a patient’s quality of life.

As the field of MPN treatment continues to evolve, it’s essential to recognize that treatment success is measured not just in the body but also in the mind. Dr. Hobbs believes that making sure patients are well-informed and have a clear understanding of their disease and treatment is a critical aspect of success, and this is an area where clinicians can make a significant impact.

The CALR gene studies, for example, have shown promise in reducing CALR mutation, which correlates with improvement in counts and fibrosis, and this is just the beginning of changing endpoints in trials. As research continues to advance, it’s likely that we’ll see more targeted therapies and better outcomes for MPN patients.