Innovating in Haematology | Exciting New Research from the 65th ASH Annual Meeting and Exposition

Let’s talk research abstracts and presentations. As I write this, I am on a flight back to London Heathrow from San Diego, which was a marathon of clinical, research, and industry meetings, presentations, and more. Of the thousands of colleagues who attended and presented at the 65th American Society of Haematology Annual Meeting and Exposition (ASH), a few really stayed with me as truly exciting innovations in the improvement of new therapies, access, outcomes, and care for people living with rare and challenging conditions.

I kicked off day 1 of ASH with a press briefing, where colleagues from Bavaria, Hong Kong, the UK, and the US presented their innovations in research. I was deeply fascinated by the work being done by Dr Fabian Müller in leveraging CD19-targeting chimeric antigen receptor (CAR) T cells and showing the impact in B cell malignancies . CD19 CAR T cells also target autoreactive B cells that trigger autoimmune diseases (AID) including systemic lupus erythematosus (SLE), idiopathic inflammatory myositis (IIM) and systemic sclerosis (SSc). Achieving long-term remission in AID with standard therapy therefore remains challenging and usually necessitates long-term treatment.

Dr Müller’s aim and success were to test whether CD19 CAR T cells achieve a deeper reset of B cells, eradicate autoimmunity, and achieve lasting drug-free remission in autoantibody-dependent AID. While the need for a longer follow-up period was noted, Dr Müller reported what is considered an unprecedented and remarkable drug-free remission with good tolerability, an ongoing investigator-led trial now underway to further build upon the understanding of safety and efficacy.

Later in the exposition, I had the chance to explore some of the inspiring new work presented at ASH’s poster walk. Dr Shirley D’Sa and colleagues at Sanofi presented some amazing work on cold agglutinin disease (CAD) – a rare autoimmune chronic haemolytic disorder that causes the production of monoclonal autoantibodies that bind to red blood cells at temperatures below normal core body temperature, and in turn cause cells to aggregate. Dr D’Sa’s work focused on a Phase 1b open-label study that evaluated the safety, tolerability, effect on haemolysis, and pharmacodynamics (PD)/pharmacokinetics (PK) of a single intravenous (IV) dose of SAR445088.

A second-generation complement inhibitor, SAR445088’s impact on complement-mediated haemolysis was assessed in 12 patients as an initial proof of concept in CAD, identifying no safety concerns and that the therapy was generally well tolerated. With a 15-week sustained classical complement inhibition, control of haemolysis, and improvement in anaemia, this work has highlighted some exciting promise for the CAD community.

Our own collaborations with Pfizer have seen two pieces presented at ASH. Within the therapeutic insights space, Dr Kim Summers’ work sought to characterise?the side effects, Health-Related Quality of Life (HRQoL), and wearable-captured sleep and activity metrics of SCD patients in the UK, before and after treatment initiation with Voxelotor . From both patient-reported feedback and remote metric monitoring, early trends were identified in this cohort that demonstrated significantly higher HRQoL-linked EQ-5D-5L scores in voxelotor treated patients compared to a current standard of care, as well as at a pre- and post-initiation level within the voxelotor cohort itself. With some early trends regarding sleep quality and activity levels tracked by an FDA-cleared device, this highlights an interesting future avenue for ongoing therapeutic impact monitoring.

Alongside colleagues at Pfizer, ASH also saw us present work that utilised AI to amplify the patient voice – a piece that was well received by colleagues across the week. Highlighting key health inequity challenges for the SCD population including limited access to emergency care, low levels of empathy from HCPs, racial bias, and stigmatisation, this generated a critical contribution to what is currently an under-researched area through a novel and quantifiable Social Media Listening approach. As all research and innovation stem from the patient voice, understanding this and the unmet need for patients and carers, while embracing AI to support an unbiased view, is a key next step in improving education and overall service improvements.

It was truly a pleasure to see colleagues Dr Jahanzaib Khwaja and Professor Ashu Wechalekar present new work in amyloidosis, with an oral presentation focused on re-assessing currently validated cardiac staging systems for the disease . In their oral presentation titled ‘Limited Utility of Mayo 2012 Cardiac Staging System for Risk Stratification of Patients with Advanced Cardiac AL Amyloidosis’, Dr Khwaja and Professor Wechalekar discussed the analysis of a uniformly treated cohort of 1,275 patients, in order to unpick the predictive performance and robustness of this staging system.?

Critically, while advanced-stage cardiac involvement remains a prognostic predictor of adverse outcomes in amyloidosis, they found that European modified staging was able to provide a stronger predictive value for poor outcomes and distinguish between the most advanced disease stages in a way that Mayo 2012 staging was not. However, with treatment appearing to have a marked impact on the predictive capabilities of these staging systems, this work stressed the need for revalidation to ensure that there is a better reflection of the current treatment pathways for amyloidosis – a vital factor in future clinic assessments and clinical trial design.

I could go on for days writing about the extraordinary efforts put in by clinical, research, industry colleagues and patients in delivering some of the most cutting-edge research, however, I trust that this provides a valuable window into our passion for research. For colleagues that we met at ASH and for those we did not have a chance to touch base with, thank you all again for sharing your innovations with the community. We would love to continue to keep in touch and continue advancing research that benefits patients, together.