Combining janus kinase (JAK) inhibitors with agents that target parallel pathways or enhance hematopoiesis may enhance efficacy and/or mitigate on-target myelosuppression in patients with myelofibrosis, according to a recent review. This has the potential to extend benefits seen with JAK-inhibitor monotherapy.

The authors note the agents that are approved or currently under investigation for the treatment of myelofibrosis and review combination strategies.

Complex molecular architecture of myelofibrosis with clonal evolution plays a role in disease progression/transformation. These molecular pathways may explain the heterogeneous benefits obtained by JAK-inhibitors in patients with the disorder. In addition, the genetic and epigenetic mutations appear to work in concert with overactive JAK/STAT signaling and contribute to myelofibrosis pathogenesis and prognosis, suggesting a potential to exploit them as potential therapeutic targets.