CML Session Summaries from EHA2026 Congress - Day 3

June 2026 - We're bringing you highlights from the EHA2026 Congress with summaries of selected scientific sessions on CML.

Education Session – Chronic myeloid leukemia

 Chair: Kateřina Machová Poláková (Prague)

The EHA2026 Education Session on CML provided a broad overview of the biological mechanisms that underlie leukemic stem cell persistence, immune control and treatment-free remission (TFR), and the increasingly individualised approach to frontline therapy. 
The presentations highlighted the importance of the bone marrow niche and inflammatory pathways in maintaining residual disease, the central role of immune surveillance, particularly natural killer (NK) cells, in successful TFR, along with the need to tailor treatment strategies according to disease biology, patient characteristics, and therapeutic goals. Together, the talks reinforced the concept that future progress in CML will depend not only on more potent BCR::ABL1 inhibition, but also on targeting the microenvironment, understanding immune mechanisms, and addressing the heterogeneity of the disease. 

Our key takeaways from the presentations:

Presentation 1:

The crosstalk between CML and the niche

Speaker: Mirle Schemionek (Aachen)

“Leukemic stem cell persistence is not solely an intrinsic property of the cell, but is strongly influenced by a permissive and dynamically changing microenvironment.”
– Mirle Schemionek

Key points:

• Inflammatory signalling sustains leukemic stem cell persistence
  Leukemic stem cells survive despite complete BCR::ABL1 inhibition, with inflammatory pathways such as JAK/STAT and NF-κB contributing to treatment resistance. Preclinical studies showed that targeting these pathways enhances stem cell eradication.
• The bone marrow niche actively supports residual disease
  CML remodels the stromal and vascular microenvironment, creating a permissive niche that maintains quiescent, TKI-resistant stem cells. Mesenchymal stromal cells and adipogenic progenitors play key roles in this process.
• Myelofibrosis at diagnosis predicts poorer treatment-free remission outcomes
  Patients presenting with bone marrow fibrosis were more likely to experience molecular relapse after TKI discontinuation, suggesting that fibrosis reflects a niche favourable to leukemic stem cell persistence.
• Megakaryocytes emerge as active niche-remodelling cells
  CML-associated megakaryocytes promoted angiogenesis and fibrosis-associated changes and showed increased production of TGF-β, indicating that they may contribute to both stem cell quiescence and disease persistence.
• Spatial organisation of the bone marrow changes during disease progression
  Recent spatial and single-cell studies demonstrated profound alterations in vascular architecture and stem cell localisation, emphasising that the niche evolves throughout disease development.
• Niche-directed therapies may complement TKIs in the future
  Emerging clinical data with anti-inflammatory approaches and preclinical studies targeting stromal interactions suggest that combining TKI therapy with niche-targeted strategies could improve eradication of residual disease.

Presentation 2:

Immune surveillance and treatment-free remission in CML

Speaker: Satu Mustjoki (Helsinki)

“Treatment-free remission is not simply determined by residual leukemia cells, but by the interaction between leukemic cells and the immune system.”– Satu Mustjoki

Key points:

• CML patients exhibit a distinct immune profile at diagnosis
  Increased immune suppressor populations and altered checkpoint molecule expression distinguish CML from other leukemias and may influence treatment responses.
• Immune composition changes during TKI therapy
  Treatment restores immune function, including normalisation of NK-cell activity and reduction of inhibitory checkpoint expression, suggesting that TKIs have important immunomodulatory effects.
• Immune parameters correlate with molecular response and TFR success
  The number and phenotype of immune cells are closely linked to treatment outcomes, and immune biomarkers may outperform traditional clinical predictors in identifying patients likely to achieve deep responses.
• Natural killer cells appear central to successful treatment discontinuation
  Multiple studies consistently showed that higher numbers of mature and functionally active NK cells are associated with sustained TFR, highlighting innate immunity as a key component of disease control.
• Additional mutations beyond BCR::ABL1 may influence TFR outcomes
  Mutations in epigenetic modifier genes were more common in patients who relapsed after treatment discontinuation, suggesting that leukemia biology and immune surveillance jointly determine TFR success.
• Future strategies may focus on boosting immune responses
  Approaches involving interferon, checkpoint inhibition, vaccines, and NK-cell activating therapies are being explored to enhance immune control of residual leukemia and improve TFR rates.

Presentation 3:

Choosing wisely from different treatment options

Speaker: Delphine Réa (Paris)

“CML is not a homogeneous disease, and treatment decisions should reflect both biological and clinical heterogeneity.” – Delphine Réa

Key points: 

• CML is a biologically and clinically heterogeneous disease
  Prognosis is influenced not only by traditional risk scores but also by transcript type, additional cytogenetic abnormalities, and mutations beyond BCR::ABL1. Future management will require a more refined definition of high-risk disease using both baseline and dynamic parameters.
• Treatment selection should be individualised according to disease and patient characteristics
  Age, comorbidities, treatment priorities and quality-of-life considerations should all be incorporated into frontline treatment decisions, emphasising a personalised approach to therapy.
• More potent TKIs improve molecular responses and may increase opportunities for TFR
  Second-generation TKIs and asciminib offer deeper molecular responses and lower risks of resistance, particularly in patients with intermediate- and high-risk disease, although longer follow-up is required for asciminib.
• Safety, tolerability and quality of life are essential components of treatment decisions
  Chronic toxicities and off-target effects influence long-term adherence and patient satisfaction. Dose optimisation and careful management of comorbidities are critical to maintaining treatment success.
• The ultimate goal should extend beyond lifelong disease control
  The question "Why should CML remain a chronic condition?" highlights the need to pursue deeper responses and curative strategies rather than accepting indefinite therapy as the endpoint for all patients. Better identification of patients unlikely to achieve deep molecular remission or successful TFR is needed.
• Future clinical trials should address the unmet needs of distinct patient subgroups
  Rather than applying the same strategy to all patients, future studies should focus on populations at high risk of resistance, failure to achieve deep molecular response, or unsuccessful TKI discontinuation.