EHA 2026 Lifetime Achievement Awardee Claire Harrison Reflects on JAK Inhibitors and the Future of Myeloproliferative Neoplasms
核心洞察
Claire Harrison received the European Hematology Association (EHA) 2026 Lifetime Achievement Award for her pioneering work in myeloproliferative neoplasms (MPN).
The landmark COMFORT-II Phase 3 trial established JAK inhibitors as the first effective therapy for myelofibrosis (搜索), rapidly improving symptoms, shrinking spleens, and extending survival.
Emerging targeted therapies, including a novel Type II JAK inhibitor, the anti-CALR monoclonal antibody INCA033989, and the SENTRY combination of selinexor plus ruxolitinib, signal a shift toward disease modification.
Claire Harrison, Professor of Myeloproliferative Neoplasms and Clinical Director at Guy's and St Thomas' NHS Foundation Trust, UK, has been awarded the European Hematology Association (EHA) 2026 Lifetime Achievement Award. In an interview with EMJ, she reflected on her pioneering work in myeloproliferative neoplasms (MPN), including the landmark COMFORT-II trial and the transformative impact of Janus kinase (JAK) inhibitors on patients with myelofibrosis (搜索).
The COMFORT-II Turning Point
Harrison led the first JAK inhibitor trial in Europe, the COMFORT-II Phase 3 trial, which she described as a turning point for patients with myelofibrosis (搜索). Before the advent of JAK inhibitors, there was no effective therapy for these patients. "We could offer them a transplant, but we only started to do that in the latter part of the 1990s. And, as your readers will know, 95% of patients cannot have a transplant," she explained.
The benefits delivered by JAK inhibitors exceeded expectations. Although the JAK2 (搜索) target differs fundamentally from the BCR-ABL target of imatinib in chronic myeloid leukaemia, and the inhibitors are not mutation specific, patients improved rapidly. "In the study, we had to call them after a couple of days on drug, and, in the end, we were all fighting who was going to call them because the patients were feeling so much better," Harrison recalled.
Clinically, spleens shrank and symptoms improved, with problematic features such as night sweats and pruritus resolving. Survival data were equally striking. "As we further analysed the data, we saw that patients were living longer. This became very clear when we observed the patients on the control arm of the study. In the end, the differences were so stark we had to stop the patients on drug versus on the control arm coming at the same time."
Harrison also acknowledged the limitations of these agents. "While these drugs are very effective, they have a limited effect for patients. They are not turning the dial and modifying the disease to a significant extent. Patients are living longer and better, but, ultimately, they are still dying of disease."
Refining Disease Classification
Harrison highlighted the limitations of traditional MPN terminology, noting that conditions such as essential thrombocythemia (搜索) (ET), polycythaemia vera (搜索) (PV), and myelofibrosis (搜索) were described toward the end of the 19th and early 20th century and are not based on a biological foundation. Patients frequently present with overlapping features or are in transition between disease states.
She emphasised the need to refine disease descriptions based on molecular biology. "Almost 100% of patients with PV have a JAK2 (搜索) mutation, and 50% of patients with ET have a JAK2 mutation." She pointed to a poster presentation at EHA 2026 showing that young patients with JAK2-mutant ET are very similar to young patients with JAK2-mutant PV.
Emerging Targeted Therapies
Harrison expressed enthusiasm for the expanding pipeline of targeted therapies in the MPN space. "For the first time in this meeting, we're seeing data for a novel Type II JAK inhibitor that may be more mutation specific and less liable to resistance." She also highlighted INCA033989, a monoclonal antibody targeting calreticulin (搜索) (CALR), the second most common MPN mutation, alongside a pipeline of other CALR-targeting modalities.
Supportive care therapies addressing anaemia were also noted, including elritercept, a TGF-β superfamily ligand trap, and DISC0974. Finally, she cited the SENTRY combination study of selinexor plus ruxolitinib as delivering a survival benefit for patients.
Harrison also raised the possibility that some patients may not require treatment at all, noting that patients with no driver mutation and a high platelet count—so-called triple negative thrombocytosis—may not need treatment, as therapy is associated with potential harm.
Reducing Thrombosis and Disease Progression
Thrombosis, haemorrhage, and disease progression remain significant concerns for patients with MPN. Harrison noted that most treatments for PV and ET have focused on reducing thrombosis risk, with progress made but no ability yet to return a patient's risk to that of someone without an MPN. She pointed toward more aggressive treatment, a focus on lifestyle, careful consideration of anticoagulants, and possibly drugs revolutionising diabetic care.
On disease progression, she highlighted that treatments reducing the JAK2 (搜索) mutant allele burden by 50%, achievable with agents such as interferon or ruxolitinib, mark a likely improvement in overall and progression-free survival. For myelofibrosis (搜索), she described the SENTRY trial's survival benefit as "really important," while calling for longer-term data to understand its mechanism.
The Role of Patients and the Next Decade
Harrison underscored the centrality of patient organisations such as MPN Voice and Blood Cancer UK, describing their role in advocacy, raising awareness, early diagnosis, and campaigning for adoption of new therapies. "I think patients have to be front and centre of what we're doing," she said.
Looking ahead, Harrison expressed hope that the next decade will move MPN care "from the era of Dameshek, through molecular discovery and new drugs, toward disease modification, so that we can have patients either being cured, or living with very minimal disease." She defined minimal disease as a state in which patients have good quality of life and a degree of certainty about the future, adding, "I definitely think we are on the verge of something very close to this for our patients."