From symptom scales to regulatory endpoints: the evolution and clinical impact of patient-reported outcome measures in myeloproliferative neoplasms

TL;DR

This paper reviews how patient-reported outcome measures have evolved to assess symptoms in myeloproliferative neoplasms, improving clinical trials and patient care.

Contribution

The paper outlines the development and clinical impact of MPN-specific PROMs, emphasizing their role in precision care.

Findings

MPN-specific PROMs like MF-SAF and MPN-SAF have been crucial in regulatory approvals for treatments like ruxolitinib.

The TSS50 endpoint is standard in trials, but continuous TSS evaluation may better capture treatment effects.

PROMs are increasingly used in clinical practice for symptom monitoring and personalized decision-making.

Abstract

Myeloproliferative neoplasms (MPNs) are symptom-driven hematologic malignancies characterized by persistent and heterogeneous symptom burden that significantly impairs health-related quality of life (HRQoL). This burden is intrinsically linked to MPN pathophysiology, including splenomegaly, inflammatory cytokine release, and microvascular dysfunction, underscoring the need for MPN-specific patient-reported outcome measures (PROMs) to quantitatively assess symptoms and sensitively capture treatment responses. Initial instruments such as the Myelofibrosis Symptom Assessment Form (MF-SAF) and MPN Symptom Assessment Form (MPN-SAF) evaluated both symptom burden and HRQoL. To meet regulatory standards for JAK inhibitor trials, subsequent versions, such as MF-SAF v2.0 and the MPN-SAF Total Symptom Score (TSS), shifted focus toward symptom-specific endpoints, with a ≥ 50% reduction in TSS (TSS50) considered a clinically meaningful response. To improve consistency and methodological rigor, the MF-SAF was further refined into version 4.0, which has served as a primary endpoint in pivotal trials such as MOMENTUM, often in combination with validated generic HRQoL instruments. These PROMs have played a pivotal role in securing regulatory approvals for agents such as ruxolitinib and momelotinib. While TSS50 remains the standard endpoint in clinical trials, its dichotomous nature presents limitations; emerging evidence suggests that evaluating TSS as a continuous variable may offer greater sensitivity in capturing treatment effects. In clinical practice, the MPN-SAF TSS is increasingly used to guide symptom monitoring and personalized decision-making. This review outlines the evolution, validation, and clinical impact of MPNs-symptom-specific PROMs, underscoring their growing role in delivering precision, patient-centered care.

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