Pharmacotherapeutic advances for splenomegaly in myelofibrosis

by Selleckchem | Apr 01 2023

Introduction: Myelofibrosis is a hematologic malignancy with a variety of clinical manifestations including splenomegaly, which is present in approximately 80% of newly diagnosed patients. JAK inhibitors are the mainstay of pharmacologic treatment for splenomegaly in myelofibrosis, although spleen size reduction is not universal, and the duration of benefit is only moderately durable.

Areas covered: We first discuss the pathobiology of splenomegaly in myelofibrosis before detailing approved and novel pharmacotherapies that can reduce spleen size while also highlighting non-pharmacologic approaches. In this review, efficacy of these treatments is measured solely by spleen volume reduction, acknowledging that other outcome measures such as symptom improvement and survival are also critical.

Expert opinion: Currently, ruxolitinib can be administered to the majority of frontline patients although those with severe thrombocytopenia should receive pacritinib to address spleen burden. Momelotinib may be particularly well suited for patients with significant anemia and novel combination treatments in clinical development may improve the depth and duration of spleen responses. After frontline treatment failure, fedratinib, or pacritinib are commercial options for patients with persistent symptomatic splenomegaly. Novel agents given alone or in combination with a JAK inhibitor are being explored in trials, which may ameliorate splenomegaly and ultimately improve disease progression.

Comments：

Myelofibrosis is a rare and complex hematologic malignancy characterized by the abnormal growth of bone marrow cells, which can lead to the development of fibrous scar tissue in the bone marrow, causing anemia, fatigue, and other symptoms. Approximately 80% of patients with myelofibrosis have splenomegaly, which can cause discomfort, pain, and other complications.

JAK inhibitors are currently the primary pharmacological treatment for myelofibrosis, targeting the underlying disease mechanism. Ruxolitinib is the most widely used JAK inhibitor and has been shown to reduce spleen size and improve symptoms in many patients. However, not all patients respond equally to ruxolitinib, and the duration of response can vary.

Alternative JAK inhibitors, such as pacritinib and fedratinib, may be more suitable for patients with certain characteristics, such as severe thrombocytopenia or intolerance to ruxolitinib. Momelotinib is another JAK inhibitor that has shown promise in reducing spleen size and improving symptoms in patients with myelofibrosis and significant anemia.

Non-pharmacological approaches, such as radiation therapy and splenectomy, can also reduce spleen size and improve symptoms in some patients. However, these approaches are not without risks and should be considered on a case-by-case basis.

Several novel pharmacological approaches are currently in development, including combination therapies that may improve the depth and duration of spleen responses. These approaches include the use of JAK inhibitors in combination with other targeted therapies or immunotherapies.

Overall, the management of splenomegaly in myelofibrosis is complex and requires an individualized approach. Patients and their healthcare providers should carefully consider the risks and benefits of various treatment options and weigh the impact of spleen size reduction on overall disease progression and quality of life.