From Blurred Lines to Guidelines for Myeloproliferative Neoplasms

The MPN guidelines are in a format that will be familiar to those who have used NCCN guidelines before, and provide updates that may not be familiar to all. One such example is the risk stratification for ET. As trainees, many of us were brought up on the classic thrombohemorrhagic model for risk stratification, in which those patients younger than 60 years who have never had a thrombosis are considered low-risk, and all others are high-risk. Low-risk patients were relegated to daily aspirin alone, while the high-risk were given cytoreductive therapy. However, we know that there are other factors that influence the risk of thrombosis in these patients, such as JAK2  mutational status. Therefore, the panel elected to build its ET management algorithm using the revised International Prognosis Score in Essential Thrombocythemia-Thrombosis (IPSETThrombosis) model (Figure).

The panel also took to task the prognostic relevance of other mutations in PV and ET (Table). Next generation sequencing (NGS) panels are becoming cheaper, faster, and more readily available. Patients, through robust social networks and information sharing, are aware of these tests, and are requesting them. Although, the prognostic significance of many mutations is unknown, and actionable targets are limited, many practicing hematologists are now faced with interpreting these panels on a day-to-day basis.

Although consensus opinion still plays a role in the formation of guidelines, quality research in the field continues, and evidence-based practices are becoming more commonplace. With that in mind, the panel members evaluated the level of evidence on which each recommendation was based. This is done with respect to the efficacy, safety, and affordability of the regimen as well as the quality and consistency of the published evidence. This is then translated into a visual tool called Evidence Blocks™ and published with the guideline. Fortunately, many ongoing trials have the potential to change practice, such as the MPD-RC 112 study, which randomly assigned high-risk PV and ET patients between pegylated interferon-α-2 and hydroxyurea, and for which the results will need to be rapidly assessed and incorporated into the guidelines.

While the lines between the MPNs may be blurred, evidence-based consensus guidelines can help bring things into focus. The expansion of the U.S.-based NCCN guidelines to include the diagnosis and treatment of PV and ET is a big step forward. Of course, they are far from perfect, so the question is: How can we improve them?

Please excuse the back-of-the-envelope exercise here, but a simple ClinicalTrials.gov search using the term “polycythemia vera” yields 230 hits, whereas a search for “breast cancer” yields 7,701 hits (accessed from ClinicalTrials.gov on 19 Sep 2017). If you adjust this for the U.S. prevalence of PV (148,000) and breast cancer (3,327,000), there are approximately 155 studies per 100,000 US patients with PV, and approximately 231 studies per 1,000,000 U.S. patients with breast cancer. Although neither overly scientific nor rigorous, this method does highlight the need for more studies. Evidence generated from clinical and translational studies serves as the building material for future additions to the guidelines. Of course we are referring to quality evidence with thoughtful inclusion criteria and meaningful endpoints, but that is a discussion for another time.