Allogeneic hematopoietic cell transplantation (HCT) appears to be superior to the best available nontransplant therapies (BAT), such as fedratinib, momelotinib, ruxolitinib, splenectomy, and splenic radiation, following first-line JAK inhibitor (JAKi) therapy failure in patients with symptomatic myelofibrosis (MF), according to a recently published study in the American Journal of Hematology.

Since the US Food and Drug Administration (FDA) approval of the JAKi ruxolitinib over a decade ago, JAKi therapy has become the standard of care for patients with symptomatic MF. However, there is currently scarce literature regarding the effectiveness of different second-line therapy options.

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“The FDA approval of additional JAKi, fedratinib and pacritinib, along with the development of novel therapies has broadened the available options; but it is not clear if second-line therapies have improved the poor prognosis,” the author wrote.

In light of the scarce literature comparing HCT and BAT, the authors performed a retrospective study including over 80 patients with symptomatic MF who received either HCT or BAT following JAKi therapy failure at the Princess Margaret Cancer Centre in Toronto, Canada between 2011 and 2022 and met the eligibility criteria.

Baseline clinical and laboratory data were available for all of the patients included in the study. The primary endpoint was overall survival (OS), and the secondary outcome measure was transformation-free survival (TFS). Statistical analysis was conducted through univariate analysis.

The OS in the group receiving HTC was approximately 46 months; in contrast, the OS of patients receiving BAT was 24 months. The median TFS rates were 51 and 22 months, respectively. Although OS was similar in both groups during the first 12 months, there was a marked difference after that point.

Based on the results of the study, the authors recommend HTC for all eligible patients after initial JAKi therapy failure.

“The therapeutic landscape of MF is rapidly evolving and strategies to reduce transplant-related complications, especially for nontraditional/mismatched donor sources, along with development of novel agents with disease modifying activity are needed to improve outcomes of patients with first-line JAKi therapy failure,” the authors concluded.


England JT, Atenafu EG, Kennedy JA, et al. Comparison of clinical outcomes between transplant and nontransplant therapies in myelofibrosis following failure of first‐line JAK‐inhibitor. Am J Hematol. Published online February 22, 2023. doi:10.1002/ajh.26890