Tracing the decision-making process for myelofibrosis: diagnosis, stratification, and management of ruxolitinib therapy in real-word practice

Abstract

The management of patients with myelofibrosis (MF) has dramatically changed since the introduction of ruxolitinib as a tailored treatment strategy. However, the perceptions about the use of this drug in clinical practice remain, at times, a matter of discussion. We conducted a survey about the diagnostic evaluation, prognostic assessment, and management of ruxolitinib in real-life clinical practice in 18 Italian hematology centers. At diagnosis, most hematologists do not use genetically or molecularly inspired score systems to assess prognosis, mainly due to scarce availability of next-generation sequencing (NGS) methodology, with NGS conversely reserved only for a subset of lower-risk MF patients with the aim of possibly improving the treatment strategy. Some common points in the management of ruxolitinib were 1) clinical triggers for ruxolitinib therapy, regardless of risk category; 2) evaluation of infectious risk before the starting of the drug; and 3) schedule of monitoring during the first 12 weeks with the need, in some instances, of supportive treatment. Further development of international recommendations and insights will allow the achievement of common criteria for the management of ruxolitinib in MF, before and after treatment, and for the definition of response and failure.

How the coronavirus pandemic has affected the clinical management of Philadelphia-negative chronic myeloproliferative neoplasms in Italy—a GIMEMA MPN WP survey

“…Notably, we documented no substantial difference in practice in colleagues with more (>10) years of experience, or who followed COVID-19-positive patients, or who work in the northern Italian regions most affected by the pandemic. This remarkable uniformity is probably owed to Diagnostic procedures remained consistent to standard criteria, with most patients receiving molecular and histology evaluations during the pandemic, as already described in Italy [4,5,7,8]. The therapeutic approach was also adherent to international guidelines, with phlebotomies for HCT > 45%, initiation of cytoreduction in patients at high thrombotic risk, and no treatment adjustment in most patients.…”

Management of Myelofibrosis during Treatment with Ruxolitinib: A Real-World Perspective in Case of Resistance and/or Intolerance

“…As with our first survey [ 11 ], participants were selected from the overall Italian geographical region and included physicians with extensive experience in treating myeloproliferative neoplasms and those with less experience, representing a real-world scenario. Overall, 28 hematologists all across Italy completed the survey; 13 with less experience (less than 50 MF patients treated with ruxolitinib in their hospital) and 15 with higher experience (≥50 MF patients treated with ruxolitinib).…”

“…The “MPN Lab” collaboration was established in March 2018 to examine experiences, perspectives, and proposals on the management of MF and PV from 18 Italian hematology centers. Their first survey was published in 2020 and described the processes involved in diagnosing, stratification, and managing MF patients in real-world practice [ 11 ]. A second survey, consisting of 27 questions, was then developed to assess the identification of resistant and intolerant MF patients, the role of allogeneic transplant, and physicians’ perceptions on novel therapeutic strategies.…”

The clinical dilemma of JAK inhibitor failure in myelofibrosis: Predictive characteristics and outcomes

“…However, PD may take other forms, including worsening anemia and/or thrombocytopenia, progressive myeloproliferative neoplasms symptoms or leukocytosis, or extramedullary hematopoiesis, compromising organ function or causing pain. In recent years, stringent criteria for ruxolitinib failure have been adopted in the design and analysis of some clinical trials 9,10 ; however, discordance among clinicians in defining ruxolitinib failure persists in real‐world practice 11 . Here, we explore the characteristics and outcomes of patients with MF who discontinue JAKi treatment because of resistance, progression, or intolerance.…”

“…In recent years, stringent criteria for ruxolitinib failure have been adopted in the design and analysis of some clinical trials 9,10 ; however, discordance among clinicians in defining ruxolitinib failure persists in real-world practice. 11 Here, we explore the characteristics and outcomes of patients with MF who discontinue JAKi treatment because of resistance, progression, or intolerance.…”