BSH 2023 | The value of novel JAK2 and CALR-targeted therapies in MPNs
Claire Harrison, MD, FRCP, FRCPath, Guy’s & St Thomas’ NHS Foundation Trust, London, UK, discusses the relevance of JAK2- and CALR-targeted therapies for patients with myeloproliferative neoplasms (MPNs). Prof. Harrison explains that the discovery of the JAK2 mutation has led to the development of many effective therapy options for patients, and that studies with anti-CALR antibodies show promise for treating patients with this mutation. Prof. Harrison further highlights the value of other strategies, such as bispecific antibodies (BsAbs), CAR-T cells, vaccinations, and the JAK inhibitor ruxolitinib. This interview took place at the 63rd Annual Scientific Meeting of the British Society for Haematology (BSH) 2023, held in Birmingham, UK.
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Transcript (edited for clarity)
So, at the present time we are really at a probably another key juncture in the MPN field, in many ways the discovery of the JAK2 mutation was symbolic because Janus is a Roman god of the gateway. The door between what is now and the subliminal kind of transition into the future. So, the discovery of the JAK2 mutation led to an explosion of new therapies and new options for patients which are very impactful...
So, at the present time we are really at a probably another key juncture in the MPN field, in many ways the discovery of the JAK2 mutation was symbolic because Janus is a Roman god of the gateway. The door between what is now and the subliminal kind of transition into the future. So, the discovery of the JAK2 mutation led to an explosion of new therapies and new options for patients which are very impactful. But right now, following on from the work that colleagues in Australia and Denmark have done, and the beautiful plenary discussion at ASH with the generation of a mutant CALR antibody which appears to be very effective in vitro and in a mouse model, we are I think at the dawn of a new therapeutic landscape for patients with MPN, maybe thinking about treating CALR-mutated patients in a totally different way to the way that we would treat JAK2 mutated patients. Aside from the Incyte monoclonal antibody, there are currently studies with vaccination strategies actually importantly, both against JAK2 and CALR combining with immune checkpoint inhibition and probably shortly there will also be other strategies, for example, with bispecific antibodies and CAR-T directed therapy. So, I would encourage colleagues if they’ve got a difficult patient who’s got a CALR mutation and a tricky disease to think about the availability of these kind of studies because they’re quite likely, hopefully, to be effective. But for JAK2-mutated disease, I think the data with interferon and from the MAJIC-PV study, suggesting that if we can target JAK2 with ruxolitinib and/or a different JAK inhibitor and interferon, that might be a very effective strategy.
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