Pharmacotherapeutic advances for splenomegaly in myelofibrosis

ABSTRACT

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.

KEYWORDS:

• Splenomegaly
• myelofibrosis
• myeloproliferative neoplasms
• JAK inhibition

Article highlights

• Splenomegaly is common in patients with myelofibrosis

• Currently approved pharmacotherapies for the treatment of splenomegaly are JAK inhibitor and include ruxolitinib, fedratinib and pacritinib

• Ruxolitinib is the most commonly used upfront therapy, although pacritinib should be given in patients with severe thrombocytopenia

• Novel therapies are being evaluated in the front line and JAK inhibitor failure setting which may improve the depth and duration of spleen response

• In appropriate patients, non-pharmacologic approaches may be required for persistent and severe splenomegaly

Declaration of interest

D Tremblay has received contracted research funding paid to his institution from CTI Biopharma, Astellas Pharma and Gilead and received consulting fees from CTI Biopharma, AbbVie, Sierra Oncology, GSK and Cogent.

J Mascarenhas has received contracted research funding paid to his institution from AbbVie, BMS, Celgene, CTI BioPharma, Geron, Incyte, Kartos, Merck, Novartis, PharmaEssentia, and Roche, and has received consulting fees from AbbVie, BMS, Celgene, Constellation Pharmaceutical, CTI BioPharma, Galecto, Geron, Incyte, Kartos, Karyopharm, Novartis, PharmaEssentia, and Sierra Oncology.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.