Effective Treatment of Low-Risk Acute Gvhd With Itacitinib Monotherapy

Authors

Aaron Etra
Alexandra Capellini
Amin Alousi
Monzr M Al Malki
Hannah Choe
Zachariah DeFilipp
William J Hogan
Carrie L Kitko
Francis Ayuk
Janna Baez
Isha Gandhi
Stelios Kasikis
Sigrun Gleich
Elizabeth Hexner
Matthias Hoepting
Urvi Kapoor
Steven Kowalyk
Deukwoo Kwon
Amelia Langston
Marco Mielcarek
George Morales
Umut Özbek
Muna Qayed
Ran Reshef
Wolf Rösler
Nikolaos Spyrou
Rachel Young
Yi-Bin Chen
James L M Ferrara
John E Levine

Publication Date

2-2-2023

Journal

Blood

Abstract

The standard primary treatment for acute graft-versus-host disease (GVHD) requires prolonged, high-dose systemic corticosteroids (SCSs) that delay reconstitution of the immune system. We used validated clinical and biomarker staging criteria to identify a group of patients with low-risk (LR) GVHD that is very likely to respond to SCS. We hypothesized that itacitinib, a selective JAK1 inhibitor, would effectively treat LR GVHD without SCS. We treated 70 patients with LR GVHD in a multicenter, phase 2 trial (NCT03846479) with 28 days of itacitinib 200 mg/d (responders could receive a second 28-day cycle), and we compared their outcomes to those of 140 contemporaneous, matched control patients treated with SCSs. More patients responded to itacitinib within 7 days (81% vs 66%, P = .02), and response rates at day 28 were very high for both groups (89% vs 86%, P = .67), with few symptomatic flares (11% vs 12%, P = .88). Fewer itacitinib-treated patients developed a serious infection within 90 days (27% vs 42%, P = .04) due to fewer viral and fungal infections. Grade ≥3 cytopenias were similar between groups except for less severe leukopenia with itacitinib (16% vs 31%, P = .02). No other grade ≥3 adverse events occurred in >10% of itacitinib-treated patients. There were no significant differences between groups at 1 year for nonrelapse mortality (4% vs 11%, P = .21), relapse (18% vs 21%, P = .64), chronic GVHD (28% vs 33%, P = .33), or survival (88% vs 80%, P = .11). Itacitinib monotherapy seems to be a safe and effective alternative to SCS treatment for LR GVHD and deserves further investigation.

Keywords

Humans, Graft vs Host Disease, Treatment Outcome, Acetonitriles, Pyrazoles, Adrenal Cortex Hormones, Hematopoietic Stem Cell Transplantation

DOI

10.1182/blood.2022017442

PMID

36095841

PMCID

PMC9936304

PubMedCentral® Posted Date

9-14-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes