Modified Delphi Process to Develop Best Practice Recommendations for Myelofibrosis Management in Routine Clinical Practice in the Asia-Pacific Region (The APAC-MF Alliance)
Authors: Gill Harinder , Choi Chul Won , Than Hein , Hou Hsin-An , Jung Chul Won , Kwong Yok-Lam , Leung Garret M. K. , Ooi Melissa G. M. , Rojnuckarin Ponlapat , Ross David M. , Shih Lee-Yung , Takenaka Katsuto , Teo Winnie Z. Y. , Kirito Keita 
Published: December 2024

Background: While international treatment guidelines for myelofibrosis (MF) have contributed to the standardization of best clinical practice and patient care globally, a need remains in the Asia-Pacific (APAC) region for treatment recommendations that take into account local epidemiology, healthcare infrastructure, and resource availability. In response, a Steering Committee (SC) of expert hematologists from Asia and Australia developed consensus statements (CSs) to optimize MF treatment in the APAC region. Herein, we present updated results of the program following the final round of extended faculty (EF) voting.

Objectives: To develop APAC region-specific, evidence- and consensus-based recommendations for routine MF management, which offer practical strategies to support clinicians and guide therapeutic decision-making.

Methods: A modified Delphi methodology was used to draft and agree CSs in response to 13 clinical questions representing unmet needs in the management of patients with MF in the APAC region. An SC was formed of 14 expert APAC hematologists who identified these questions across four themes: 1) thresholds for anemia, and when to initiate or modify treatment; 2) when to initiate or modify treatment for thrombocytopenia; 3) Janus kinase inhibitor failure and what would warrant switching treatment; and, 4) appropriate risk stratification models for MF in the APAC region. Findings from a systematic literature review, along with clinical insights of the SC, were used to draft the CSs. An APAC EF, including expert hematologists and representatives from patient advocacy groups, voted on the CSs, with consensus reached when 75% of respondents agreed within a range of 7-9 on a 9-point scale (1=strongly disagree, 9=strongly agree). Voters scoring &lt;7 were required to provide written rationale, used to refine the CSs for re-voting.

Results: After two voting rounds, all CSs reached a high level of consensus (12/13 in the range of 90-100% and 1/13 in the range of 80-90%). In the first voting round, 12/13 CSs reached consensus among voters (hematologists [n=57], and patient representatives from MPN-JAPAN [n=1] and MPN Alliance Australia [n=1]). The CS that did not reach consensus related to how MF management changes if thrombocytopenia evolves during treatment; EF feedback highlighted concerns about the efficacy, risk, and availability of treatments in the APAC region (including danazol, IMiDs, and eltrombopag). Eltrombopag was removed as a recommended treatment option due to limited access and supporting evidence, while danazol and IMiDs were retained. The SC also identified a further five CSs that would benefit from refinement, including CSs on anemia treatment and use of risk stratification models. For CSs under the anemia theme, feedback included concerns on access to treatment options (including erythropoiesis-stimulating agents, danazol, and thalidomide), the link between anemia and weight loss, and the lack of robust evidence and guidelines for iron chelation use. Revisions included removing ‘weight loss’ from symptoms to consider when evaluating the need for anemia treatment (fatigue, shortness of breath, and poor appetite were retained) and more specific wording around treatment options for anemia and iron overload. For the risk stratification theme, feedback emphasized the lack of reimbursement for next-generation sequencing-integrated models and the relative pros and cons of these models vs more widely used scores. Revisions included updates to a proposed algorithm for prognostic score selection in MF. A second voting round was held, and consensus was achieved for all six of the resubmitted CSs. This iterative process aimed to ensure broad consensus and recommendations that meet the needs of clinicians and patients in the APAC region.

Conclusions: The APAC-MF consensus program established a framework for addressing key challenges in MF care within the APAC region. Consensus was achieved after two voting rounds among both the APAC SC hematologists and EF members on strategies to address the multifaceted aspects of MF care. This program highlighted the importance of considering regional nuance and individualized therapy, and we believe that continued collaboration and refinement will enhance care quality across the APAC region. This work will be developed into a clinical resource to support healthcare professionals in the care of patients with MF in the APAC region.