Anemia is a major contributor to symptom burden, poor quality of life (QOL), and adverse outcomes in myelofibrosis. However, increasing hemoglobin levels through a transfusion does not always translate into improved patient-reported outcomes. Confounding factors such as thrombocytopenia and inflammation also contribute significantly to symptom burden. Treatments including ESAs and luspatercept can improve anemia, while JAK/ACVR1 inhibitors may offer broader benefits.

One of the most challenging unmet needs in the treatment of myelofibrosis is the management of anemia. Anemia occurs in almost all patients with myelofibrosis at some point during their disease course. Not only does it reflect more aggressive disease with worsened survival but it also greatly impacts QOL. As many therapies that are US Food and Drug Administration (FDA) approved for the treatment of myelofibrosis exacerbate anemia, this can be a very challenging clinical situation.

Anemia contributes to a patient’s QOL in many ways. Low hemoglobin levels are associated with fatigue, shortness of breath, and dizziness. However, even after a transfusion, a patient may still not feel well despite having increased hemoglobin levels (eg, 9 or 10 g/dL). In these cases, there are probably other contributing factors. There are some data suggesting that platelet levels can contribute to symptom burden, including fatigue, but there are other nonhematologic factors that can also contribute. For example, many patients with myeloproliferative neoplasms also have depression, which can exacerbate fatigue. Additionally, patients with myeloproliferative neoplasms have an increased risk of being socially isolated, which can also contribute to fatigue.

There are some therapeutic approaches that we can use to treat anemia-related symptoms. For example, ESAs and luspatercept have both been shown to improve anemia in approximately 50% of patients with myelofibrosis. Although luspatercept is not yet FDA approved for myelofibrosis, there are data suggesting that it has a benefit, especially for those patients who are on ruxolitinib. Another option is the androgen-like medication danazol. In addition, for patients who are symptomatic with splenomegaly, JAK/ACVR1 inhibitors such as momelotinib and pacritinib may increase hemoglobin levels, as well as improve symptoms and spleen size. For patients who respond well to and tolerate JAK inhibitors, JAK/ACVR1 inhibitors provide a much more comprehensive benefit, since JAK inhibition also reduces inflammatory symptoms. However, when these medications are ineffective, patients often will require transfusions.

Despite multiple advances in the management of anemia, it remains a significant challenge in the treatment of myelofibrosis. Additional therapies are needed to address this problem and improve QOL.