JAKi Therapy Yields Safe and Effective Results in Portal Hypertensive MPNs

A retrospective study was performed at Princess Margaret Hospital, Canada, to assess patients with myeloproliferative neoplasms (MPNs) who received JAK inhibitor (JAKi) therapy for portal hypertension (PH) without underlying splanchnic circulation thrombosis (ST). All data were presented at the 2021 Annual American Society of Hematology (ASH) Meeting.

“Splenomegaly is a characteristic feature of MPNs that can be ameliorated by JAKi. Up to one-third of patients also experience PH. Thrombosis of the splanchnic circulation is the most widely recognized etiology of PH in MPNs, however, PH also occurs in the absence of thrombosis,” explained Marta Davidson, MD, PhD, Princess Margaret Hospital, Canada, and co-investigators.

Records of patients with MPN were assessed between 1998 and 2021 and limited the study’s population based upon whether patients began JAKi therapy following diagnosis of PH. Those who underwent esophagogastroduodenoscopy (EGD) and had endoscopic evidence of PH were included (n=33).

“The primary endpoint was palpable spleen reduction at 24 weeks. Secondary endpoints were best palpable spleen reduction within one year of starting JAKi, improvement in PH severity as determined by serial EGD assessments during JAKi therapy, overall survival (OS), and grade 3 adverse events (AEs) or higher,” continued Dr Davidson and co-investigators.

Notably, 13 out of 33 patients experienced ST prior to the start of JAKi. Findings confirm both the number of younger patients and those with PH-related complications were higher in patients with underlying ST (5/20 [25%] vs 9/13 [69%], P=0.01).

Further, the median palpable spleen change at 24 weeks of therapy, and the best palpable spleen reduction within the first year of therapy, were -40.5% and -50% in the entire cohort, respectively. Improved spleen responses with JAKi therapy was observed in PH patients without prior ST compared to those with underlying ST.

“Of 21 patients with serial EGDs during JAKi treatment, improvement in PH severity as observed in 8 (38%). There were no differences in survival between patients with and without prior ST,” said Dr Davidson and co-authors.

Reported grade 3 AEs included anemia (15%), thrombocytopenia (15%), neutropenia (3%), and suspected Wernicke encephalopathy associated with Momelotinib (3%). No treatment-related deaths occurred.

“In this observational study, JAKi appears to be safe and effective in MPN patients complicated by PH, with a trend towards improved spleen responses among portal hypertensive patients without splanchnic circulation thrombosis,” concluded Dr Davidson, et al.—Alexa Stoia