Pre-Transplant Ruxolitinib Potentially Linked With Improved Non-Relapse Mortality, Survival Benefits in Myelofibrosis

Treatment with Janus kinase (JAK) inhibitors such as ruxolitinib (Jakafi; Incyte Corporation) prior to hematopoietic cell transplantation (HCT) could be associated with improved non-relapse mortality (NRM) and survival benefits in patients with myelofibrosis (MF), even in patients who could typically proceed directly to HCT, according to an abstract published in Transplantation and Cellular Therapy that was presented at the 2025 Tandem Meetings of ASTCT and CIBMTR, which took place February 12, 2025, to February 15, 2025 in Honolulu, Hawaii.¹

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Ruxolitinib has been used for over a decade for the treatment of patients with intermediate or high-risk MF following its regulatory approval by the FDA in 2011. Numerous studies have indicated the positive effects of ruxolitinib in MF; not only does the therapy provide a greater reduction in spleen volume compared with placebo, but it also can address underlying fibrosis that leads to severe complications.^2,3

However, ruxolitinib has often been studied in the context of patients who were not considered candidates for HCT, which could be curative for patients with MF but presents significant health burdens that necessitate the exclusion of many from the treatment. The corresponding decrease in splenomegaly, a hallmark of MF, and improvement in symptoms with ruxolitinib have led some patients to become eligible for HCT after treatment. As a result, questions have been raised as to whether JAK inhibitor therapy such as ruxolitinib should be administered prior to HCT in patients with MF who are eligible.¹

The study investigators conducted a phase 2 prospective single-center trial of ruxolitinib followed by HCT in adult patients with primary and secondary MF between 2014 and 2020, with a primary end point of 2-year overall survival (OS). To be considered a candidate for HCT, patients had to have at least an intermediate-1 designation based on the Dynamic International Prognostic Staging Score (DIPSS); the patients were not required to have symptoms of MF or splenomegaly. Participants had to be treated with ruxolitinib for at least 8 weeks, with a plan to taper off treatment at least 4 days prior to HCT conditioning.¹

In the study population, 61 patients (59% primary MF, 70% DIPSS intermediate 2 or high risk) proceeded to HCT following a median of 7 months on ruxolitinib. Among the patients who had symptoms prior to ruxolitinib, 55% had no or improved symptoms pre-HCT. Without including patients who underwent splenectomy (n = 7), 38% of patients had a greater than 10% decrease in splenomegaly, while another 36% were stable, according to the investigators.¹

At day 100, NRM was 5%, whereas it was 13% at 1-year follow-up, compared with 26% at 1-year in non-JAK inhibitor-treated control patients at the medical center of the investigators. There was a median follow-up of 5.2 years for OS observations; at 2 years, OS was 79% (95% CI, 69%-90%), while at 5 years, it was 74% (95% CI, 64%-86%). For the historical controls’ cohort, 2-year OS was 60% and 5-year OS was 57%, according to the study authors.¹

Due to the risk of graft-vesus-host disease (GVHD) in this patient population, the investigators measured the incidence of GVHD in patients treated with JAK inhibitors and those not. According to the investigators, the incidence of day 100 acute grade 2 to 4 GVHD was 71%, and grade 3 to 4 was 19%, rates like those of historical controls. At 3 years, chronic GVHD of any grade had been diagnosed in 52%, with moderate to severe GVHD documented in 44% of patients. In a critical observation, time on pre-HCT JAK inhibitor therapy was associated with a lower risk of acute GVHD, while DIPSS of intermediate-2 or higher was associated with more chronic GVHD.¹

“Pre-HCT JAK inhibitors may be associated with NRM and survival benefits even for MF patients who could otherwise proceed directly to HCT,” the study authors concluded. “The relationship between GVHD and JAK-inhibitor therapy/DIPSS score is of unclear etiology and needs to be explored.”¹

REFERENCES

1. Salit RB, Fan X, Ratsamee N, et al. Phase II prospective study of intentional pre-treatment of hematopoietic cell transplant eligible myelofibrosis patients with ruxolitinib. Transplant and Cell Therapy. 2025;31(2):S107-S108. doi:10.1016/j.jtct.2025.01.170

2. Deisseroth A, Kaminskas E, Grillo J, et al. U.S. Food and Drug Administration approval: Ruxolitinib for the treatment of patients with intermediate and high-risk myelofibrosis. Clin Cancer Res. 2025;18(12):3212-3217. doi:10.1158/1078-0432.CCR-12-0653

3. Gerlach A. Study finds ruxolitinib may slow fibrosis progression in myelofibrosis. Pharmacy Times. Published September 24, 2024. Accessed February 26, 2025. https://www.pharmacytimes.com/view/study-finds-ruxolitinib-may-slow-fibrosis-progression-in-myelofibrosis