Establishing consensus-based recommendations on first-line ruxolitinib failure and transition for myelofibrosis in Korea: A modified Delphi study
Sung-Eun Lee, Seug Yun Yoon, Junshik Hong, Seung Hyun Nam, Min Kyoung Kim, Ho Jin Shin, Sung Hwa Bae, Jinny Park, Yeung-Chul Mun, Soo-Mee Bang, Chul Won Choi, Chul Won Jung, Jong Ho Won, Ha-Young Kwon, Chanmee Park, Sung-Yong KimBackground
Janus kinase (JAK) inhibitors are used as first-line treatment for myelofibrosis (MF) and are associated with improvements in splenomegaly and disease-related symptoms. However, a substantial proportion of patients experience treatment failure or intolerance, and outcomes after discontinuation remain poor. Although international groups have proposed criteria for JAK inhibitor failure, standardized and operational definitions applicable to real-world practice, particularly in South Korea, are lacking.
Objectives
This study aimed to establish expert consensus on defining first-line ruxolitinib failure and to develop practical transition strategies tailored to the Korean clinical context.
Design
This was a non-interventional qualitative study using a modified Delphi methodology.
Methods
Fourteen hematologists specializing in MF in South Korea participated in a two-round web-based Delphi survey followed by a final consensus meeting. Consensus-driving questions covered five domains: ruxolitinib failure, loss of therapeutic response, disease progression, intolerance, and transition strategies. Consensus was defined as ≥80% agreement using predefined criteria.
Results
Consensus was achieved on key operational definitions across the major domains, although several intolerance-related items remained unresolved. Refractory MF was defined as inadequate spleen response (<10% reduction after ≥6 months of therapy) or inadequate symptom response (<30% reduction in MPN-SAF score after ≥3 months of therapy). Clear criteria for response loss, progressive splenomegaly, hematologic progression, and intolerance were established. Structured tapering of ruxolitinib (≥4 weeks), management of ruxolitinib discontinuation syndrome, and transition strategies including use of second-line JAK inhibitors and prioritization of allogeneic hematopoietic stem cell transplantation were agreed upon.
Conclusion
This modified Delphi study successfully established consensus-based recommendations for ruxolitinib failure and treatment transition in MF management in Korea. The findings provide practical criteria for identifying treatment failure and guiding transition strategies, ensuring alignment with global best practices while addressing local healthcare considerations.