New research presented at the 2025 Society of Hematologic Oncology (SOHO) Annual Meeting highlights how doctors are improving the use of JAK inhibitors—medications that have changed the outlook for people living with myelofibrosis (MF).
Researchers from the University of Bologna shared how early treatment, careful dose adjustments, and regular monitoring can help patients benefit the most from these therapies.
What Are JAK Inhibitors?
JAK inhibitors block a pathway in the body (the JAK/STAT pathway) that drives inflammation and abnormal blood cell growth in MF. These drugs help control symptoms such as fatigue, night sweats, and spleen enlargement and, in some patients, can even extend survival.
Four JAK inhibitors are currently available:
- Ruxolitinib – the first approved drug in this class, which helps about half of patients shrink an enlarged spleen and feel better overall.
- Fedratinib – works well even for people with low platelet counts or those whose disease returns after earlier treatment.
- Momelotinib – may help improve energy levels and reduce the need for blood transfusions in people who also have anemia.
- Pacritinib – designed for patients who have very low platelet counts.
Each medicine has its strengths, and doctors choose among them based on a patient’s symptoms, blood counts, and overall health.
Why Early Treatment Matters
Starting JAK inhibitor therapy early—before severe symptoms or organ changes develop—can lead to better responses and fewer complications. Patients with mild disease may still be monitored closely without treatment, but for those with significant fatigue, pain, or enlarged spleen, starting sooner helps improve quality of life and long-term outcomes.
Adjusting and Monitoring Treatment
Once treatment begins, dosing is important. Underdosing, especially with ruxolitinib, may lead to weaker results and reduced survival. Doctors closely monitor blood counts during the first few months to adjust treatment and manage possible side effects like low red blood cells, low platelets, or mild infections.
If symptoms or spleen size do not improve after about three to six months, doctors reassess the treatment plan. This may mean adjusting the dose, switching to another JAK inhibitor, or considering clinical trials exploring new combination therapies.
When JAK Inhibitors Stop Working
Resistance or reduced response can occur over time because of new genetic changes in the disease. In these cases, the medication may be slowly stopped to prevent withdrawal symptoms, and a different JAK inhibitor or a bone marrow (stem cell) transplant might be considered.
For some patients, JAK inhibitors help control the disease long enough to make a stem cell transplant possible—the only treatment that can potentially cure MF.
Looking Ahead
Researchers are now testing combinations that pair JAK inhibitors with other targeted therapies to further improve response and durability. Personalized treatment based on each patient’s genetics and symptoms is becoming a key goal.
The researchers in this study emphasized that JAK inhibitor therapy works best when started early, monitored carefully, and adjusted to fit each patient’s needs.
Reference
Palandri, F. Abstract EXABS-187-MPN, SOHO 2025, 2-7 Sept.
