A Global Call for IFN Treatment of MPNs

Outside of Europe it is common practice to treat patients with MPNs with hydroxyurea, which, according to Dr Hasselbalch, may induce acute leukemia after long-term treatment.


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In a 2014 open letter to the MPN Research Foundation, Dr Hasselbalch urged the scientific community to reconsider the use of IFN alfa-2 in place of hydroxyurea for the treatment of patients with MPNs.7 “The world is divided in two. A world that has easy access to IFN and a world that does not have easy access to IFN. The large majority of US patients [with MPNs] do not have access to IFN because it is used off-label and, therefore, the insurance companies will not insure the patients unless they have a doctor who is very keen to treat the patient with IFN,” he stated.

Moving Forward With Combination Therapies and Vaccination Trials

With monotherapy, approximately 20% to 30% of patients receiving IFN alfa-2 stop treatment due to side effects. In patients who do not tolerate IFN alfa-2 monotherapy, IFN elicits an inflammatory response. To combat this, Dr Hasselbalch and colleagues are using COMBI, a combination of IFN alfa-2 and the potent anti-inflammatory agent ruxolitinib to dampen the inflammation in these patients and allow for continuation of IFN treatment.

MPNs are linked to chronic inflammation and are described as inflammatory diseases. Dr Hasselbalch and colleagues noted that the genetic variants associated with MPNs are also associated with increased reactive oxygen species and inflammatory responses. Thus, the hypothesis that chronic inflammation elicits MPNs is currently being investigated.

In addition to IFN alfa-2 therapy, Dr Hasselbalch and colleagues have introduced vaccination trials in Denmark. In these trials, patients who have achieved minimal residual disease with IFN treatment are administered peptide vaccines “to enhance the immune system to kill the remaining MPN clone.”

“The ultimate goal is to cure the patients of MPN,” said Dr Hasselbalch. “That is where we are in Denmark: on the path towards the cure of patients with MPNs by early intervention with IFN combined with vaccination. From the bottom of my heart, I believe that the future looks bright for patients with MPNs worldwide.”

References

1. Hasselbalch HC, Holmström MO. Perspectives on interferon-alpha in the treatment of polycythemia vera and related myeloproliferative neoplasms: minimal residual disease and cure? [published online September 10, 2018] Semin Immunopathol. doi: 10.1007/s00281-018-0700-2

2. Cantell K, Hirvonen S, Kauppinen HL, Myllylä G. Production of interferon in human leukocytes from normal donors with the use of Sendai virus. Methods Enzymol. 1981;78:29-38.

3. Ludwig H, Linkesch W, Gisslinger H, et al. Interferon-alfa corrects thrombocytosis in patients with myeloproliferative disorders. Cancer Immunol Immunother. 1987;25(3):266-273. doi: 10.1007/BF00199157

4. Linkesch W, Gisslinger H, Ludwig H, Flener R, Sinzinger H. Therapy with interferon (recombinant IFN-alpha-2C) in myeloproliferative diseases with severe thrombocytoses. Acta Med Austriaca. 1985;12(5):123-127.

5. Riley CH, Hansen M, Brimnes MK, et al. Expansion of circulating CD56 bright natural killer cells in patients with JAK2-positive chronic myeloproliferative neoplasms during treatment with interferon-α. Eur J Haematol. 2015;94(3):227-234.

6. Skov V, Riley CH, Thomassen M, et al. The impact of interferon-alpha2 on HLA genes in patients with polycythemia vera and related neoplasms. Leuk Lymphoma. 2017;58(8):1914-1921. doi: 10.1080/10428194.2016.1262032

7. Hasselbalch HC. An open letter to the MPN community in the United States. MPN Research Foundation website. http://www.mpnresearchfoundation.org/interferonHasselbalch2014. Published March 2014. Accessed October 24, 2018.