Selinexor Monotherapy for Cytoreduction in BCR::ABL1-Negative Myeloproliferative Neoplasms
Key claim: A phase II single-arm trial is evaluating selinexor monotherapy as cytoreductive treatment in Philadelphia chromosome-negative MPNs (PV, ET, PMF) to assess its effectiveness and safety over 6 months.
Abstract
Myeloproliferative neoplasms are chronic blood cancers in which the bone marrow produces too many blood cells. Patients with Philadelphia chromosome-negative myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia, and primary myelofibrosis, may need treatment to reduce high blood cell counts, relieve disease-related symptoms, and lower the risk of complications. However, currently available cytoreductive treatments may be ineffective, poorly tolerated, or inconvenient for some patients.
Selinexor is an oral selective inhibitor of nuclear export that has shown antitumor activity in several hematologic malignancies. This study will evaluate the effectiveness and safety of selinexor used alone as cytoreductive treatment in patients with Philadelphia chromosome-negative myeloproliferative neoplasms who have an indication for cytoreductive therapy.
This is a prospective, single-arm, open-label phase II study conducted at a single center. Eligible participants will receive oral selinexor, with dose adjustments based on tolerability and blood cell counts. Participants will be followed for treatment response, symptom improvement, and side effects for up to 6 months. The results of this study may help determine whether selinexor could provide a potential treatment option for patients with Philadelphia chromosome-negative myeloproliferative neoplasms who have limited cytoreductive therapy choices.
Why this matters
Selinexor has so far been studied in MPN almost exclusively as a ruxolitinib or pacritinib combination partner in myelofibrosis (e.g., SENTRY). A monotherapy cytoreduction trial spanning PV, ET, and PMF represents the first opportunity to evaluate XPO1 nuclear export inhibition as a standalone mechanism for disease control across the three classical BCR::ABL1-negative subtypes, and will generate the first cross-subtype comparative data on whether this mechanism’s effect differs between erythrocytosis-, thrombocytosis-, and fibrosis-dominant disease.