MDS-053 Drug-Induced Hypertension in Classical Philadelphia-Negative Myeloproliferative Neoplasms (MPNs): Systematic Review.

INTRODUCTION: Secondary hypertension, e.g., drug-induced hypertension (DI-HTN), can occur in patients with solid/hematological cancers. However, the relationship between anticancer therapy and DI-HTN in classical Philadelphia-negative MPNs is unclear. OBJECTIVE: Investigate this research question via a systematic review. METHODS: Comprehensive search in PubMed/MEDLINE, SCOPUS and Web of Science. Publications that reported DI-HTN as an adverse effect (AE) of anticancer therapy for MPNs were included in the qualitative/quantitative synthesis. RESULTS: Search strategy identified 590 records. After removal of duplicates/screening of titles/abstracts, 87 papers were selected for full-text review. After inclusion/exclusion criteria were applied, 12 manuscripts entered into the qualitative/quantitative synthesis. Ruxolitinib's effect (RUX) on systolic (SBP)/diastolic (DBP) blood pressure is controversial: one study reported no effect on SBP/DBP, whereas in another SBP but not DBP increased. In RESPONSE-2 trial, DI-HTN developed as non-hematological AE [grade 3-4 (6%, n=5); grade 1-2 (3%, n=2)] in 9% (n=7) of 74 polycythemia vera (PV) patients enrolled. RESPONSE-2 secondary analyses reported RUX-induced hypertension as the most frequent grade 3/4 AE in the RUX/RUX cross-over arms. Interferon did not cause DI-HTN in RESPONSE and RESPONSE-2 trials. RUX+decitabine in accelerated/blast phase MPNs (n=25) caused 3 DI-HTN cases: grade 1/2 (n=2), grade 3+ AE (n=1). RUX+decitabine resulted in 2 DI-HTN cases (grade 3 AE in 21 MPNs in accelerated/blast phase). RUX+danazol in 14 primary/secondary myelofibrosis (PMF/SMF) subjects lead to 1 DI-HTN case (n=1, 7.1%) in a multicentric phase 2 study. Anagrelide caused DI-HTN as AE in 9 essential thrombocythemia (ET) subjects, however, hydroxyurea caused DI-HTN in 1 of 146 patients. Italian ET registry retrospective evaluation reported DI-HTN in 3.5% (n=8) of 232 anagrelide-treated subjects. DI-HTN occurred as dose-limiting toxicity in an open-label, dose-escalation assessment of AT9283 (Aurora kinases inhibitor) in advanced PMF/SMF and refractory AML. Givinostat caused DI-HTN (grade 3 AE) in 1 of 50 PV subjects. CONCLUSIONS: RUX (alone/in combination with decitabine/danazol), anagrelide, AT9283, and givinostat can cause DI-HTN in classical Philadelphia-negative MPNs.