MPN-036 Treatment Failure and Transition to Next-Line Therapy in Myelofibrosis: A Modified Delphi Panel Approach.

Abstract

Ruxolitinib (RUX) is a first-line treatment for intermediate or high-risk myelofibrosis (MF) and was shown to improve splenomegaly and MF symptoms; however, patients experience loss of response and discontinuation rates are high (40%-70%). New treatment options have emerged for patients who are intolerant to or progress on RUX. The aim of the study was to establish how treatment failure can be defined in real-world practice and develop parameters to guide appropriate transition to next-line therapy. A 3-round modified Delphi panel was conducted with 14 hematologist-oncologists who had been a principal investigator on ≥1 clinical trial or involved in NCCN Guidelines for Myeloproliferative Neoplasms around the USA. Two survey rounds were completed via online questionnaires and scored using 9-point Likert scales, followed by a consensus meeting to resolve conflicting statements. Agreement was defined as ≥80% of respondents scoring 7-9 and disagreement 1-3. Eighty-four statements were agreed upon to define RUX failure. Consensus was reached for primary refractory treatment failure, defined as patients with no spleen/symptom response within ≥3 months while receiving a maximally tolerated dose. Loss of spleen/symptom response within ≥1 month following initial response or progressive disease, including to blast phase, were agreed upon as indicative of RUX failure. Intolerance can indicate RUX failure, presenting as treatment-emergent toxicities deemed unacceptable to the patient after ≥4 weeks of treatment. Additional consensus statements suggest that patient-reported symptoms of fatigue, poor concentration, inactivity, and bone pain were too general to define RUX failure versus other specific MF symptoms, i.e., night sweats. Following RUX failure, consensus recommendations suggest that next-line treatment should be guided by patient characteristics to mitigate risk of withdrawal and should start as soon as clinically appropriate. This research provides expert consensus on recognizing RUX failure in those with no treatment response or progression based on spleen and symptom control and intolerance. These definitions can be utilized to add guidance to future clinical guidelines or help providers recognize RUX failure in real-world practice. The study was supported by Bristol Myers Squibb. This work was previously presented at the 27th National Comprehensive Cancer Network (NCCN) Annual Conference, 2022.