Despite the identification of JAK mutations and the development of targeted inhibitors, there remain significant unmet needs for patients with myeloproliferative
neoplasms. Identification of the myeloproliferative
neoplasm populations not currently benefiting from
JAK inhibitor therapy highlights the therapeutic deficits still present in this heterogeneous stem cell
malignancy. While JAK inhibition has provided significant benefits for patients with intermediate-2 or high-risk
myelofibrosis and in patients with
polycythemia vera in the second-line setting,
JAK inhibitor monotherapy is not approved and not appropriate for all patients with myeloproliferative
neoplasms. Continued investigation into additional
JAK inhibitors, combination
therapy, and novel pathway
therapeutics remains key to improving outcomes for all patients with myeloproliferative
neoplasms. While therapeutic advances in the
JAK inhibitor arena or involving alternative pathways are crucial to improving outcomes in myeloproliferative
neoplasms, it is also important to reconsider the role of constitutional symptoms in affected patients as an indication for treatment with agents, such as
JAK inhibitors, that can mitigate these debilitating symptoms. In this review, we demonstrate the evolving landscape of clinical investigations that address the important therapeutic needs of patients with myeloproliferative
neoplasms.