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Ruxolitinib in Patients with Myelofibrosis Reduces Incidence of Acute and Chronic GVHD
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Key Takeaways
- Ruxolitinib significantly reduced acute and chronic GVHD incidence in myelofibrosis patients undergoing HCT compared to standard prophylaxis.
- The trial involved 25 patients, with a median age of 66, treated with ruxolitinib pre-, peri-, and post-HCT.
At 1- and 2-year follow-up points, ruxolitinib led to considerable improvements in survival in patients with myelofibrosis who develop graft-versus-host disease (GVHD).
In patients with myelofibrosis (MF) who received pre-, peri-, and post-transplant ruxolitinib (Jakfafi; Incyte Corporation), the incidence of both acute and chronic graft-versus-host disease (GVHD) was considerably reduced compared with patients given standard GVHD prophylaxis, according to the results of a phase 2 single-center prospective clinical trial published in Transplantation and Cellular Therapy.1
Graft-versus-host disease is a possible complication of transplantation in patients with myelofibrosis. | Image Credit: © inews77 - stock.adobe.com
Ruxolitinib has been demonstrated to improve outcomes in patients with MF prior to undergoing hematopoietic cell transplantation (HCT), even in patients who could typically proceed directly with HCT, signifying its pre-treatment effectiveness. Still, a major risk of non-relapse mortality in these patients is present due to the development of GVHD following HCT, which occurs when transplanted cells attack host cells in the patient’s body. This risk remains despite the improvement in outcomes in patients with MF undergoing HCT.1-3
In the research center of the current investigators, the incidence of grade 2 to 4 acute (74%) and all grades chronic (52%) GVHD with standard GVHD prophylaxis remains high. Ruxolitinib was granted regulatory approval by the FDA in 2021 for the treatment of chronic GVHD after failure of 1 or 2 lines of systemic therapy in adults and pediatrics and received approval in 2019 for the treatment of steroid-refractory acute GVHD; however, it has not been fully determined whether ruxolitinib is useful in the GVHD prophylaxis setting.1,4
Therefore, the current investigators conducted a trial of ruxolitinib in HCT-eligible patients with primary and secondary MF pre-, peri-, and post-HCT to evaluate the incidence of grade 2 to 4 acute GVHD. For enrollment, patients had to have at least Dynamic International Prognostic Staging System (DIPSS) Intermediate-stage-1 disease, not received prior HCT, and not transformed to acute myeloid leukemia. A total of 25 patients with a median age of 66 years were enrolled in the trial between 2020 and 2024.1
Regarding baseline patient characteristics, most patients had primary MF (60%), were Janus kinase 2 (JAK2)-mutated (68%), had intermediate-2 or high-risk DIPSS (72%), and had at least 1 high molecular-risk mutation (54%). Prior to conditioning, patients were treated with ruxolitinib for a median of 6 months and continued until a median of 12 months post-HCT. Acute GVHD grade 2 to 4 was diagnosed in 36% (n = 9), and grades 3 to 4 in 8% (n = 2) of patients; importantly, only 2 patients required topical therapy.1
At 1-year, chronic GVHD was observed in 12% of patients. Two patients developed de novo chronic GVHD at over 1 year following the cessation of ruxolitinib. Critically, Kaplan Meier estimates of survival at years 1 and 2 were 100% and 87%, respectively, whereas relapse and non-relapse mortality (NRM) were each seen in 8% (n = 2) of patients, according to the study authors. Overall, the investigators observed a considerable reduction in patients developing acute and chronic GVHD when treated with ruxolitinib, necessitating further analysis of this strategy.1
It will be essential for investigators to conduct additional research on this treatment strategy, especially across different patient subgroups based on age, disease status, and prior treatments. Pharmacists should look to incorporate ruxolitinib into GVHD treatment in patients with MF who undergo HCT. Despite the strong curative potential that HCT presents, the treatment is accompanied by many risks, necessitating a strong approach to post-HCT complications.
