Feb 27, 2024

Insights from ASH 2023: Advancements in MPN Research

Róisín NicAmhlaoibh

VP Business Development

At ASH 2023, groundbreaking advancements in MPN treatment showcased potential disease-modifying therapies targeting bone marrow fibrosis. Ground Truth Labs is at the forefront, leveraging AI-powered spatial biomarkers to enhance fibrosis assessment, driving forward the development of innovative therapies.

The recent ASH 2023 conference highlighted significant progress in the development of therapeutic agents targeting bone marrow fibrosis, offering potential pathways to alter the course of Myeloproliferative Neoplasms (MPNs).

As part of this evolving landscape, Ground Truth Labs (GTL) is leveraging AI to redefine how we assess and combat bone marrow fibrosis, a key challenge in MPN management.

MPN challenges

MPNs stand as a testament to the complexity of haematological disorders, characterised by an aberrant stem cell niche that leads to excessive cytokine production, inflammatory bone marrow changes, and splenomegaly. The only definitive cure, bone marrow transplantation, remains an option for only a select few due to its significant risks, highlighting the urgent need for innovative treatment strategies.

Current treatments and their limitations

The introduction of JAK inhibitors like ruxolitinib and fedratinib has been a significant milestone in treating myelofibrosis (MF), a severe MPN subtype. However, these treatments often offer symptomatic relief without altering the disease's progression. Notably, ~50% of MF patients discontinue ruxolitinib treatment within three years due to progression or inadequate response, leading to a median overall survival of approximately 14 months post-discontinuation.

Emerging therapeutic approaches

Encouragingly, over the last several years there has been a surge in novel therapeutic agents targeting the unmet needs in MF treatment. Notable highlights from ASH 2023 include:

• Pacritinib: Vachhani et al presented data from the PERSIST-2 and PAC203 studies demonstrating pacritinib’s potential in improving platelet counts and possibly modulating the bone marrow microenvironment. Interestingly, platelet improvement and transfusion independence response correlated with improvement in bone marrow fibrosis.
• Combination Therapies:Early-phase results from combining BET inhibitors with JAK inhibitors suggest a potential reduction in inflammation and disease burden, indicating a move towards disease-modifying strategies. Lee-Hoeflich et al showed increased frequency of bone fibrosis reduction with increased dose levels of BMS-986158.
• LOX Inhibition:Preliminary results from a study of PXS-5505, a pan-LOX inhibitor, showed a reduction in collagen fibrosis in a subset of patients but reticulin fibrosis as determined by routine histopathological analysis remained stable.
• PIM1 Kinase Inhibitor:Previous preclinical studies have demonstrated a reduction in BMF and spleen size following treatment with the TP-3654 PIM1 inhibitor. Phase 1/2 data included a patient treated with TP-3654 with reduced BMF who also achieved spleen and symptom responses.

GTL's contribution to fibrosis assessment

The traditional WHO fibrosis scoring system, while widely used, is semi-quantitative and subject to inter-observer variability, which could obscure subtle treatment effects.

GTL, in collaboration with Hoffmann-La Roche, presented an AI-driven quantitative analysis to evaluate the impact of anti-fibrotic treatments like Zinpentraxin Alfa on bone marrow fibrosis. This approach, utilising digital whole slide images, provides a detailed, objective assessment of fibrotic burden and response to therapy, enhancing the precision of clinical trials without sacrificing tissue samples needed for other analyses.

We believe this technology holds great potential to complement current manual assessment, help to increase our understanding of fibrotic processes and changes during the course of disease progression.

Future directions

We continue to explore the capabilities of AI in improving the diagnostic and therapeutic landscape for MPNs and look forward to sharing more at ASH 2024 and throughout the year.

We invite collaboration, discussion, and inquiry from across the medical and scientific communities. If you're interested in learning more about our AI-driven approaches to bone marrow fibrosis assessment or wish to explore potential collaborations, we encourage you to reach out - please contact us at info@groundtruthlabs.com for more information.