For decades, treatments for myeloproliferative neoplasms (MPNs) focused on symptom relief and preventing complications like blood clots. As the field has advanced, the primary goals have remained the same: reduce constitutional symptoms such as fatigue, bone pain, and night sweats, and minimize the risks of thrombosis, including heart attacks and strokes. However, patients and advocates have long argued that these goals are not enough. They have pushed for treatment approaches that actually modify the disease course and extend survival.
Defining Treatment Success
Gabriela Hobbs, MD, the clinical director of the leukemia service at Massachusetts General Hospital, notes that treatment success varies by patient and disease type. For a low-risk patient with essential thrombocythemia (ET) who has no symptoms, success means living a normal quality of life without frequent doctor visits or unnecessary medications. When symptoms are present, success is defined by resolving anemia, reducing fatigue, or shrinking an enlarged spleen. A large spleen can cause early satiety and unintended weight loss, so managing this organ is a key part of the treatment goal.
The availability of new therapies has expanded the toolkit for treating MPNs. The U.S. Food and Drug Administration recently approved the first new ET drug in nearly 30 years, along with a first-in-class drug for polycythemia vera. This growth in options means clinicians and patients can switch medications more frequently if a current treatment fails to control blood counts or improve symptoms. Dr. Hobbs points out that while newer therapies have improved outcomes, fatigue remains a difficult challenge that current medications do not always address.
For a patient living with an MPN, the shift in focus from managing symptoms to modifying the disease represents a tangible change in daily experience. Instead of simply accepting chronic fatigue or frequent transfusions as a part of life, patients can now ask their doctors about trying different options. This shift empowers individuals to seek treatments that offer a better quality of life rather than just a temporary reduction in pain or discomfort.
Clinical Trials and Disease Modification
Research is also evolving to match the new treatment environment. Dr. Hobbs explains that targeted therapies are now being studied to attack the disease at its source, with the hope of improving marrow morphology and reducing the mutation load. Early data from studies involving the CALR gene show a decrease in mutations that correlates with improved blood counts and reduced fibrosis. Immunotherapies and PARP inhibitors are also being explored as potential disease-modifying approaches.
Looking Toward the Future
Dr. Hobbs expresses excitement regarding specific research directions. She highlights the addition of PARP inhibitors. These drugs assist the body’s own DNA repair mechanisms. Immunotherapies are also under study, specifically CALR monoclonal antibodies. Dr. Hobbs believes these approaches will be game changers for patients with CALR mutations. Early data suggests these therapies might modify the disease. Additionally, more potent and selective JAK inhibitors are showing promise. Studies combining JAK inhibitors with other treatments also report positive results. The specialist remains optimistic about the future outlook for patients.
The Bottom Line
Dr. Scandura observes that the field is lagging behind. The biological understanding of the disease and the development of therapies have moved faster than the trial endpoints. Clinical trials still rely on short-term measures. These include the Total Symptom Score and Spleen Volume Reduction indexes. Dr. Scandura notes that these fixed, binary measures have their limitations. There is a limit to how much a spleen can shrink or how much a symptom score can improve. As treatments improve, showing additional benefit with these older metrics becomes harder. Even if a therapy changes the disease course, the older measures may not capture it.