# 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.

## Key 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.