Evaluating the serial use of the Myelofibrosis Symptom Assessment Form for measuring symptomatic improvement: performance in 87 myelofibrosis patients on a JAK1 and JAK2 inhibitor (INCB018424) clinical trial

Abstract

Background: Symptomatic burden from constitutional symptoms, anemia, and splenomegaly-related symptoms are common and morbidity inducing in patients with myelofibrosis (MF). The authors previously developed a MF-specific instrument for capturing the burden of MF-associated disease-related symptoms, the Myelofibrosis Symptom Assessment Form.

Methods: The authors evaluated the usefulness of serial administration of the Myelofibrosis Symptom Assessment Form as an instrument for the assessment of symptomatic burden and improvement in conjunction with the therapeutic clinical trial of the open label phase 2 trial of the JAK1 and JAK2 inhibitor INCB018424 in patients with MF.

Results: The analysis cohort of 87 patients treated in this trial demonstrated that the instrument was comprehensive and sensitive to symptoms present at trial enrollment. In addition, baseline Myelofibrosis Symptom Assessment Form symptom scores correlated well with objective parameters such as splenomegaly and impaired performance status assessed by the 6-minute walk test. Serial administration while on therapy with INCB018424 demonstrated the instrument to be sensitive to symptomatic change, and that improvements in symptoms correlated well with objective improvements in both weight loss and performance status (6-minute walk test).

Conclusions: The use of the Myelofibrosis Symptom Assessment Form in this phase 2 trial helped characterize the symptomatic improvements observed with use of INCB018424 in MF patients. In an era of many targeted therapies undergoing testing for MF with potential symptomatic benefit, the Myelofibrosis Symptom Assessment Form may provide a useful tool for objective symptomatic assessment and potentially allow some nonrandomized comparison between therapeutic agents.

Figure 1

Median serial change over time is shown in cytokine-dependent symptoms in 87 patients with myelofibrosis treated with INCB018424. Abbreviation: MFSAF, Myelofibrosis Symptom Assessment Form.

Figure 2

Median change is shown in 4 splenomegaly-associated symptoms (abdominal discomfort/pain, ability to move/walk around, ability to bend/tie shoes, changed appetite) based on the level of spleen response after 6 cycles of therapy (ie, full, International Working Group for Myelofibrosis Research and Treatment [IWG-MRT] 50% reduction; partial, some splenic reduction but less than IWG-MRT threshold; and no response). Subjects with palpable baseline spleen and on-study responses after 6 cycles and who initiated therapy at doses of 10 mg twice daily, 15 mg twice daily, or 25 mg twice daily are included (n = 58).