Emerging Data Continue to Evolve Treatment Utilization in MPNs

Laura Joszt, MA

Emerging data are continually changing the knowledge base around how interferons should be used, despite being around for decades, in patients with myeloproliferative neoplasms (MPNs), says Raajit Rampal, MD, PhD, hematologic oncologist, associate attending physician, Memorial Sloan Kettering Cancer Center.

Transcript

How has the landscape for MPN treatment evolved since the introduction of interferons? How does it look different today?

I guess it’s more a question of utilization than the landscape, in the sense that both things like hydroxyurea and interferons and drugs, like an anagrelide for ET [essential thrombocythemia], have been around for quite some time. And I think that it hasn’t been clear for the majority of that time which drugs should be used when and by whom.

There is now randomized clinical trial data for pegylated interferon vs hydroxyurea, but more recently, particularly with regards to polycythemia vera, there’s randomized data with ropeginterferon and hydroxyurea. And at least in that data set, the [blood] count control was superior with ropeginterferon vs hydroxyurea over the course of a number of years. Initially, at 1 year, there wasn’t so much of a difference, but as time went on, there was clearly a difference that favored the use of ropeginterferon in terms of controlling the blood counts. Similarly, over time, there does seem to be a decrease in the JAK [Janus kinase] 2 mutation burden in the patients who got the ropeginterferon.

I think that there is an emerging data set that is arguing that there are benefits to interferon. Going back to the initial point here, the landscape has changed to some degree—with the introduction of something like ropeginterferon—but I think it’s more that the data is evolving, which is beginning to tell us maybe which drugs might be best for which patients. We’re not completely there by any stretch of the imagination, but the data is beginning to coalesce around the message.

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The Role of DNA Repair (XPC, XPD, XPF, and XPG) Gene Polymorphisms in the Development of Myeloproliferative Neoplasms

by , , , , , and  

Abstract

Background and Objectives: Several polymorphisms have been described in various DNA repair genes. Nucleotide excision DNA repair (NER) detects defects of DNA molecules and corrects them to restore genome integrity. We hypothesized that the XPCXPDXPF, and XPG gene polymorphisms influence the appearance of myeloproliferative neoplasms (MPNs). Materials and Methods: We investigated the XPC 1496C>T (rs2228000, XPC Ala499Val), XPC 2920A>C (rs228001, XPC Lys939Gln), XPD 2251A>C (rs13181, XPD Lys751Gln), XPF-673C>T (rs3136038), XPF 11985A>G (rs254942), and XPG 3507G>C (rs17655, XPG Asp1104His) polymorphisms by polymerase chain reaction–restriction fragment length polymorphism analysis in 393 MPN patients [153 with polycythemia vera (PV), 201 with essential thrombocythemia (ET), and 39 with primary myelofibrosis (PMF)] and 323 healthy controls. Results: Overall, we found that variant genotypes of XPD 2251A>C were associated with an increased risk of MPN (OR = 1.54, 95% CI = 1.15–2.08, p = 0.004), while XPF-673C>T and XPF 11985A>G were associated with a decreased risk of developing MPN (OR = 0.56, 95% CI = 0.42–0.76, p < 0.001; and OR = 0.26, 95% CI = 0.19–0.37, p < 0.001, respectively). Conclusions: In light of our findings, XPD 2251A>C polymorphism was associated with the risk of developing MPN and XPF-673C>T and XPF 11985A>G single nucleotide polymorphisms (SNPs) may have a protective role for MPN, while XPC 1496C>T, XPC 2920A>C, and XPG 3507G>C polymorphisms do not represent risk factors in MPN development.