The European Hematology Association (EHA)’s 2026 Congress (11–14 June; Stockholm, Sweden) brought together up to 15,000 clinicians, researchers, and allied professionals to discuss innovations spanning malignant and non-malignant hematology, precision medicine, rare diseases, and novel therapeutic strategies.
PSI’s Julia Bortsova, Head of Hematology Project Management, and Angela Cortés, Senior Medical Monitor Hematology, highlight the growing awareness of VEXAS syndrome, the rapid progress of menin-targeted therapies in acute myeloid leukemia, perspectives on CAR T-cell therapies, emerging insights into the influence of the microbiota on hematologic disease, and important advances in von Willebrand disease and sickle cell disease.
VEXAS syndrome: From recognition to management
Much attention at EHA 2026 was focused on VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome, which is still in the awareness phase. VEXAS syndrome remains a rare disorder, and clinicians are still learning to recognize the pathophysiology and clinical features; substantial discussion centered around:
- UBA1 mutations as the drivers of disease heterogeneity – different UBA1 variants are associated with differing degrees of residual UBA1 protein activity, explaining the differences in disease severity and patient outcomes. Next-generation sequencing (NGS) was highlighted as an important tool for VEXAS diagnosis as it enables comprehensive detection of UBA1 variants beyond the canonical p.Met41 hotspot, complementing targeted methods such as ddPCR and Sanger sequencing
- The ACR consensus guidance on treatment strategies for VEXAS syndrome – while the guidance on steroid use provides a more structured approach to disease management, speakers at EHA 2026 emphasized the need for steroid-sparing therapies to minimize long-term toxicity and improve disease control. Management of VEXAS syndrome is increasingly being recognized as extending beyond suppressing inflammation, and to proactively preventing associated complications. Steroid-sparing approaches – including hypomethylating agents, targeted immunomodulatory therapies, and allogeneic stem cell transplantation in selected patients – remain central to the evolving management of VEXAS syndrome
- An increased understanding of VEXAS-associated infections – opportunistic infections and severe respiratory viral disease (with these diseases being more serious in patients with specific UBA1 mutations and lymphopenia) reinforce the importance of prophylactic treatment strategies
- Recognition that VEXAS syndrome may overlap with other hematological disorders – VEXAS should be considered when patients present with systemic inflammatory disorders and unexplained cytopenia, particularly where features overlap with MDS, relapsing polychondritis, and other inflammatory conditions
The VEXAS syndrome landscape is transitioning from disease recognition to precision management. As UBA1 genotype-phenotype relationships become better understood, and diagnostic pathways mature, opportunities are emerging for targeted therapies that reduce steroid dependence, address underlying disease biology, and improve long-term outcomes. We expect expanding opportunities for biomarker-driven clinical development of safer, targeted therapies capable of controlling both inflammatory and hematological manifestations.
Menin inhibition: A new molecular era for AML
Across educational sessions and clinical presentations, menin inhibition in acute myeloid leukemia (AML) was positioned not simply as another targeted therapy, but as a new treatment paradigm for genetically defined leukemias, particularly those with KMT2A (MLL) rearrangements and NPM1 mutations.
An expanded understanding of menin biology reinforces the perception of its role as a critical epigenetic cofactor sustaining aberrant HOX and MEIS gene expression, driving leukemogenesis. By disrupting the menin-KMT2A interaction, menin inhibitors have demonstrated the ability to restore myeloid differentiation.
Clinical data presented at EHA 2026 reflected the rapid evolution of the field beyond proof-of-concept studies, demonstrating high rates of molecular remission and promising long-term outcomes:
- Revumenib: Multiple presentations, including post-hoc analyses of the AUGMENT-101 trial [1], explored its use in newly diagnosed NPM1-mutated AML, its role following allo-SCT, and combination strategies designed to overcome acquired resistance
- Mezigdomide: Early clinical experience of this CELMoD agent (in combination with revumenib) highlighted efforts to address resistance driven by acquired MEN1 mutations [2] – it is one of the first approaches designed to prolong the response to menin inhibition
AML remains one of the most investigated research areas across hematology and oncology. These advances will increase demand for central laboratory support, biomarker testing, molecular screening programs, and rapid site activation. To ensure trials are able to complete on time and sponsors can hit their approval milestones, CROs must implement longitudinal, continuous feasibility strategies to avoid any delays.
EHA 2026 demonstrated the maturation of the menin pathway from emerging target into an established therapeutic class – this mirrors how we were talking about BTK inhibitors or CAR-T cell therapies a few years ago. As clinical development expands into earlier lines of therapy, combination regimens, and maintenance settings, opportunities are emerging not only for first-generation menin inhibitors, but also for next-generation molecules, resistance-prevention strategies, companion diagnostics, and biomarker-driven clinical trials targeting genetically defined AML subgroups.
CAR T-cell therapies: From innovation to optimization
CAR T-cell therapies are an established treatment modality, and EHA 2026 demonstrated the shift in focus to refining their use in routine practice through real-world evidence, earlier intervention, and improved patient access.
Relapsed or refractory large B cell lymphomas (R/R LBCL)
Discussions about R/R LBCL centered on the three approved autologous CAR T-cell products: axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabtagene maraleucel (liso-cel). Long-term follow-up from pivotal studies, including ZUMA-7 [3], TRANSFORM [4], and BELINDA [5], alongside real-world registry data, continued to support durable remissions and manageable safety profiles in second-line treatment.
Speakers focused on practical considerations in R/R LBCL, such as toxicity management, patient selection, access to treatment, and integrating CAR T-cell therapies into routine practice. The absence of prospective head-to-head trials means treatment decisions continue to rely on cross-trial comparisons, available real-world evidence, and individual patient factors.
Mantle cell lymphoma (MCL)
Updated results from TRANSCEND MCL [6] and analyses from the CIBMTR registry [7] reinforced the durability of liso-cel in heavily pre-treated patients, demonstrating that outcomes achieved in clinical trials can be replicated in routine clinical practice – however, relapse remains a significant unmet need, with limited treatment evidence available to guide subsequent treatment strategies.
Relapsed or refractory follicular lymphoma (FL)
As described at EHA 2026, the aim is to deliver more than just response, but durable remission with time-limited therapy while maintaining QoL, minimizing toxicity, and (where possible) achieving long-term treatment-free disease control. Following ZUMA-5 [8, 9] and ELARA [10, 11], CAR T-cell therapies are an established and effective option for FL, alongside bispecific antibodies and other novel immunotherapies. Discussion focused on treatment sequencing of CAR T-cell therapies with expanding bispecific options.
Despite the success of CAR T-cell products, unmet needs remain. Relapse following therapy continues to represent a significant clinical challenge, and questions around optimal sequencing with bispecific antibodies, earlier use in treatment pathways, and improving patient access remain active areas of investigation.
CAR T-cell therapies have entered a new phase of clinical development – where operational execution and evidence generation are more important than therapeutic innovation. Real-world evidence, long-term follow-up, optimization of treatment sequencing, and improved access will shape development strategies, while emerging in vivo CAR T-cell platforms have the potential to broaden the reach of cellular therapies by addressing some of the logistical challenges associated with current autologous manufacturing processes. Experienced cell therapy sites and long-term safety follow-up infrastructure are critical to trial success.
The microbiome: A modifiable determinant of outcomes
The discussion at EHA 2026 extended well beyond descriptive microbiome studies to interventions that may actively improve treatment outcomes.
Hematopoietic stem cell transplantation
Multiple presentations demonstrated that disruption of the intestinal microbiota contributes to impaired immune reconstitution, increased susceptibility to infection, and the development of graft-versus-host disease (GVHD). New multi-omics studies linked specific microbial signatures with immune recovery and patient survival following allogeneic SCT, supporting the development of microbiome-informed risk stratification.
AML
Hematological malignancies and their treatment can disrupt gastrointestinal barrier integrity through inflammation, epithelial→mesenchymal transition and injury, extracellular matrix remodeling, and altered tight-junction function, contributing to microbiome dysbiosis. In addition, intensive chemotherapy can cause substantial gastrointestinal epithelial injury through the initiation of DNA damage and apoptosis, oxidative stress, and inflammation, increasing microbiome dysbiosis. Emerging evidence suggests that these microbiome changes correlate with infectious complications during induction therapy and may ultimately influence treatment response and clinical outcomes. Similar discussions highlighted gastrointestinal epithelial damage associated with hyperleukocytosis in acute leukemias – reinforcing the importance of preserving mucosal barrier integrity throughout treatment.
Microbiota-directed therapies
One session at EHA 2026 examined the potential of fecal microbiota transplantation to restore microbial diversity, reduce intestinal damage, and decrease the incidence of infections and GVHD following SCT. Although the approaches remain investigational, the discussion reflected growing confidence that modifying the microbiome is an important adjunct to conventional treatment.
As evidence continues to link gut microbial composition with treatment response, immune recovery, and transplant outcomes, opportunities are expanding for microbiome-based biomarkers, supportive care interventions, and combination strategies designed to improve the efficacy and tolerability of existing therapies. We are becoming better at understanding that optimizing patients’ biological environments is as important as targeting the underlying hematological malignancy itself.
Inherited blood disorders: Advances in precision care
Continued progress across benign hematology was showcased at EHA 2026 in both inherited bleeding disorders and hemoglobinopathies.
Von Willebrand disease
Discussion centered on improving diagnosis through integrating genetic testing and molecular phenotyping, enabling more accurate classification of disease subtypes and supporting personalized treatment decisions. Novel recombinant von Willebrand factor replacement therapies also featured prominently, offering the potential for more predictable PK and tailored prophylactic strategies. Sessions also explored sophisticated approaches to monitoring bleeding phenotypes and evaluating treatment efficacy in patients with complex disease presentation.
Sickle cell disease
The emphasis remained on disease-modifying therapies capable of transforming long-term outcomes. Advances in gene-editing approaches (CRISPR/Cas9-based correction of HBB mutations) alongside emerging pharmacological agents targeting hemoglobin polymerization, cellular adhesion, inflammation, and vascular dysfunction (to reduce pain crises and improve QoL) highlight continued progress. Educational sessions also highlighted the importance of multidisciplinary care, with increasing emphasis on early intervention, comprehensive disease management, and psychosocial support.
Advances in molecular diagnostics, recombinant biologics, gene editing technologies, and targeted therapeutics continue to expand opportunities for innovation in inherited blood disorders, while highlighting the growing importance of biomarkers, long-term outcomes, and patient-centric treatment strategies in clinical development.
Final thoughts
EHA 2026 reinforced that hematology is entering an increasingly personalized era. Targeted molecular approaches and immune-based treatments are reshaping the SoC. As the field evolves, success will depend not only on developing novel therapeutics, but also improving patient stratification, integrating genomic and molecular diagnostics, and generating robust long-term clinical evidence to support regulatory approval and patient treatment decisions.
Abbreviations
Allo-SCT, allogeneic stem cell therapy;
AML, acute myeloid leukemia;
CAR T-cell, Chimeric antigen receptor T cell;
Cas9, CRISPR-associated protein 9;
CELMoD, Cereblon E3 Ligase Modulatory Drugs;
CRISPR, clustered regularly interspaced short palindromic repeats;
EHA, European Hematology Association;
FL, follicular lymphoma;
GVDH, graft-versus-host disease;
HBB, hemoglobin subunit beta;
HOX, homeobox;
KMT2A (MLL), mixed-lineage leukemia gene;
MCL, mantle cell lymphoma;
MDS, myelodysplastic syndromes;
MEIS, myeloid ecotropic viral integration site 1;
NPM1, nucleophosmin 1;
PK, pharmacokinetics;
QoL, quality of life;
R/R LBCL, relapsed or refractory large B cell lymphomas;
SCT, stem cell therapy;
SoC, standard of care;
UBA1, ubiquitin-like modifier activating enzyme 1;
VEXAS, Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic.
References
1. Blachly, J.S., et al. Efficacy of revumenib in acute myeloid leukemia harboring NPM1-mutated co-mutations: Post hoc analysis of AUGMENT-101. 2026. Accessed July 2026; Available from: https://library.ehaweb.org/eha/2026/eha-2026/4207502/james.s.blachly.efficacy.of.revumenib.in.acute.myeloid.leukemia.harboring.html.
2. National Institutes of Health. A Study of Revumenib and Mezigdomide in People With Leukemia (NCT07356154). 2026. Accessed July 2026; Available from: https://clinicaltrials.gov/study/NCT07356154.
3. Locke, F.L., et al., Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma. N Engl J Med, 2022. 386(7): p. 640–654.
4. Abramson, J.S., et al., Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: primary analysis of the phase 3 TRANSFORM study. Blood, 2023. 141(14): p. 1675–1684.
5. Bishop, M.R., et al., Second-Line Tisagenlecleucel or Standard Care in Aggressive B-Cell Lymphoma. N Engl J Med, 2022. 386(7): p. 629–639.
6. Wang, M., et al., Lisocabtagene Maraleucel in Relapsed/Refractory Mantle Cell Lymphoma: Primary Analysis of the Mantle Cell Lymphoma Cohort From TRANSCEND NHL 001, a Phase I Multicenter Seamless Design Study. J Clin Oncol, 2024. 42(10): p. 1146–1157.
7. Huang, J.J., et al., Outcomes of lisocabtagene maraleucel (liso-cel) in patients (pt) with relapsed or refractory (R/R) mantle cell lymphoma (MCL): First real-world data from the CIBMTR. Journal of Clinical Oncology, 2026. 44(16_suppl): p. 7026–7026.
8. Jacobson, C.A., et al., Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): a single-arm, multicentre, phase 2 trial. Lancet Oncol, 2022. 23(1): p. 91–103.
9. Neelapu, S.S., et al., Five-Year Follow-Up Analysis of ZUMA-5: Axicabtagene Ciloleucel in Relapsed/Refractory Indolent Non-Hodgkin Lymphoma. J Clin Oncol, 2025. 43(33): p. 3573–3577.
10. Fowler, N.H., et al., Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: the phase 2 ELARA trial. Nat Med, 2022. 28(2): p. 325–332.
11. Dreyling, M., et al., Durable response after tisagenlecleucel in adults with relapsed/refractory follicular lymphoma: ELARA trial update. Blood, 2024. 143(17): p. 1713–1725.
12. Akdis, C.A., Does the epithelial barrier hypothesis explain the increase in allergy, autoimmunity and other chronic conditions? Nat Rev Immunol, 2021. 21(11): p. 739–751.
