Cytopenic myelofibrosis: prevalence, relevance, and treatment

Cytopenic myelofibrosis is increasingly recognized as a phenotype of myelofibrosis presenting with low blood counts, lower driver mutation allele burden, increased likelihood of arising de novo, i.e. primary myelofibrosis, greater genomic complexity, worse survival, and higher rates of leukemic transformation compared to the more traditional 'myeloproliferative' phenotype. Both anemia and thrombocytopenia are very common, often coexist, and can be worsened by treatment. Several JAK inhibitors with different kinome profiles are now available for routine clinical use. Additionally, ancillary therapies can also provide some, albeit non-durable, benefit.

In this review, we discuss the prevalence and clinical significance of cytopenias in myelofibrosis. We then discuss the various Janus kinase (JAK) inhibitors and ancillary therapies available with a special focus on their use in cytopenic populations, ability to improve cytopenias, and notable adverse events. Articles included were selected through literature searches using the PubMed database.

Pacritinib and momelotinib are new treatment options for patients with cytopenic myelofibrosis. These JAK inhibitors are less myelosuppressive and allow for cytopenia stabilization or improvement while providing additional benefits. It is likely that their use will expand and these newer JAK inhibitors will become backbones for future combinations with novel, 'disease modifying' agents.