COVID-19 as a mediator of interferon deficiency and hyperinflammation: Rationale for the use of JAK1/2 inhibitors in combination with interferon
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Professor Hans Hasselbalch Professor Hans Hasselbalch is Consultant Hematologist at the Department of Hematology, Roskilde Hospital, University of Copenhagen. He is former chairman of the Danish Study Group of Chronic Myeloid Neoplasms and member of the Nordic Myeloproliferative Study Group (NMPD). For many years, his professional interests have focused upon chronic myeloid neoplasms (essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF) (MPNs). His main research in MPNs is focusing upon integrated molecular (eg. gene expression profiling, epigenetics, SNPs) and immune cell studies in MPN patients before and during treatment with interferon-alpha2 (IFN-alpha2) and novel targeted therapies, including the JAK1−2 inhibitor Ruxolitinib and Histone Deacetylase inhibitor (HDACi) treatment. In this regard, Hans Hasselbalch is Principal Investigator (PI) of a Danish Multicenter Study on low-dose IFN-alpha2 in the treatment of MPNs (DALIAH) and was PI on an International Multicenter Study on the HDACi Vorinostat in the treatment of PV and ET. In 2012, Hasselbalch published in Blood his hypothesis on chronic inflammation as the trigger and driver of clonal evolution, premature atherosclerosis and second cancers in MPNs. This paper has been followed by several others and today chronic inflammation is considered a major driving force for disease progression in MPNs, having a great impact on the mutational landscape in MPNs. In this regard Hasselbalch and his MPN research have as the first shown that smoking –a huge chronic inflammation load – is a risk factor for the development of MPNs. Hasselbalch’s hypothesis prompted a Danish Multicenter Trial - The COMBI-Trial -, in which patients with PV and hyperproliferative MF are treated with a combination of pegylated interferon-alpha2 (Pegasys or PegIntron) and ruxolitinib. The results from this study are highly impressive and encouraging, published in Cancer Medicine (12 months data) and Haematologica (24 months data). This study has been followed by a safety and efficacy study of COMBI in newly diagnosed PV patients. Other research areas within MPNs – all conducted as part of Ph.D theses - include “National Registry Studies on The Co-Morbidity Burden in MPNs”, “The Role of Reactive Oxygen Species in MPNs “, “Immune Cell Studies in CALR-Mutated Patients with The Potential of Vaccination Therapy”, “Quality of Life Studies in MPNs”, and The Danish Multicenter Study of The Safety and Efficacy of Pegylated Interferon Alpha2 in MPNs (DALIAH). Hans Hasselbalch is chairman of a Clinical Academic Group (CAG) - CAG-ZIRI - within Greater Copenhagen Health Science Partners (GCHSPs), selected as a CAG in 2020. In 2021, Hans Hasselbalch has been awarded the Hagedorn Prize for excellent research within the chronic blood cancers - MPN.