Tag Archives: graft-versus-host

Ruxolitinib Discontinuation at Conditioning Does Not Increase GVHD Risk in Myelofibrosis

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May 7, 2025

Author(s): Alexandra Gerlach, Associate Editor

Stopping ruxolitinib (Jakafi; Incyte Corp) prior to the conditioning regimen may not influence graft-versus-host disease (GVHD) risk more than in patients with myelofibrosis (MF), according to data published in Cancer Immunology, Immunotherapy.1

MF is an incurable, rare hematologic malignancy that is part of a group of diseases called myeloproliferative neoplasms, which are characterized by the overproduction of red blood cells. This causes bone marrow scarring, leading to severe anemia—a key factor impacting overall survival for patients with MF. Other symptoms include fatigue, enlarged spleen, night sweats, bone pain, and weight loss. MF can develop as a primary disease or secondary to essential thrombocythemia and polycythemia vera. In some cases, it can progress to acute myeloid leukemia.2

Ruxolitinib is the standard of care for first-line treatment of patients with MF that was originally approved by the FDA in 2011 for the treatment of intermediate- and high-risk MF. It was also the first approved treatment for patients 12 years of age and older with steroid-refractory acute GVHD in 2019. Ruxolitinib is a Janus kinase (JAK) 1/2 inhibitor that targets the JAK/STAT pathway, a critical cellular signaling pathway that helps cells respond to cytokines. Identification of mutations within the JAK/STAT pathway paved the way for the development of agents such as ruxolitinib, fedratinib (Inrebic; Bristol Myers Squibb), momelotinib (Ojjaara; GSK), and pacritinib (Vonjo; CTI BioPharma).2,3

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Ruxolitinib Plus SOC Prophylaxis Is Associated With Lower Rates of GVHD in Myelofibrosis

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February 14, 2025

Author(s): Dylann Cohn-Emery

Fact checked by: Jonah Feldman

Treatment with the combination of ruxolitinib (Jakafi) and standard-of-care graft-vs-host disease (GVHD) prophylaxis led to a reduction in the rates of acute and chronic GVHD without compromising survival rates in patients with myelofibrosis undergoing hematopoietic stem cell transplantation (HCT), according to data from a phase 2 prospective study (NCT04384692) presented at the 2025 Transplantation and Cellular Therapy Meetings.1

The study conducted at Fred Hutchinson Cancer Center showed grade II to IV acute GVHD occurred in 32% of patients receiving peri-transplant ruxolitinib, whereas it occurred in 71% in a pre-transplant ruxolitinib group of a similar preliminary study. The percentage of patients with chronic GVHD at 1 year with peri-transplant ruxolitinib 12%, whereas it was 25% with pre-transplant ruxolitinib. These rates of GVHD also coincided with high overall survival (OS) rates at year 1 and 2 of 100% and 87%, respectively, in the peri-transplant ruxolitinib trial.

“The incidence of acute and chronic GVHD was markedly reduced without the expense of non-relapse mortality, relapse, or survival. It doesn’t appear that infections or transfusion needs were increased,” Rachel B. Salit, MD, associate professor at Fred Hutchinson Cancer Center, said in her presentation.

Janus kinase (JAK) inhibitors prevent activation of the JAK domain by binding to the kinase, in turn preventing STAT phosphorylation and translocation of the nucleus. This process reduces the production of pro-inflammatory cytokines. GVHD pathogenesis has shown to be affected by the JAK-STAT pathway, and JAK signaling is key in the process leading to tissue damage and inflammation.

In previous trials of ruxolitinib, such as COMFORT-I (NCT00952289) and COMFORT-II (NCT00934544), this JAK inhibition showed significantly better results in reducing symptoms and splenomegaly compared with best available therapy in patients with myelofibrosis. Additionally, the REACH1 (NCT02953678), REACH2 (NCT02913261), and REACH3 (NCT03112603) trials demonstrated significantly improved response with ruxolitinib vs best available therapy when treating patients with acute and chronic GVHD.

The preliminary study (NCT02251821) of ruxolitinib pre-transplant showed improved survival in this patient population. With a median time of 7 months on ruxolitinib, 38% of patients had more than a 10% decrease in spleen size and 36% were stable. In patients with symptoms prior to ruxolitinib, 55% had stable or improved symptoms by the time of HCT.

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