The European Society for Medical Oncology (ESMO) 2025 congress delivered important data across the haematological oncology spectrum, showcasing advances in CAR-T innovation, immunomodulatory combinations, MRD-adapted treatment strategies and integrated prognostic tools. Below, we have broken down the key abstracts that emerged from this year’s meeting.
Mechanisms of CAR-T Resistance in High-Grade B-Cell Lymphoma (LBA47)1
This late-breaking mechanistic study identified tumour-associated macrophages expressing colony stimulating factor 1 receptor (CSF1R) and triggering receptor expressed on myeloid cells 2 (TREM2) as key drivers of CAR-T failure. Despite adequate tumour infiltration, non-responders exhibited CAR-T exhaustion signatures and enriched immunosuppressive myeloid niches at baseline and post-infusion. These findings highlight the tumour microenvironment – rather than antigen loss alone – as a central determinant of CAR-T resistance and point to CSF1R-targeted or transcriptional-reprogramming strategies to restore CAR-T functionality.
CAR2219 Phase II Trial – Dual-Target CD19/CD22 CAR-T in R/R LBCL (Abstract 1240O)2
A prospective, single-arm phase II study evaluated CAR2219, a bispecific CD19/CD22-targeted CAR-T product developed to mitigate antigen escape in relapsed/refractory large B-cell lymphoma (R/R LBCL). Thirty-one patients, heavily pretreated with a median of three prior lines, successfully received CAR2219 following standard lymphodepletion. At a median follow-up of 4.2 months, the best overall response rate reached 100%, with a complete response (CR) rate of 67.7%. Median progression-free survival (PFS) and OS were not reached, and 6-month estimates were encouraging at 83% and 87.1%, respectively. Toxicities were manageable, with no grade ≥3 CRS and only one grade 3 ICANS event. The data position dual-antigen CAR-T as a promising approach to overcome single-target resistance mechanisms.
Quadruplet Immunochemotherapy for r/r ENKTL (Abstract 1241O)3
This multicentre phase II trial assessed a combination of tislelizumab, chidamide, lenalidomide, and etoposide in relapsed/refractory extranodal NK/T-cell lymphoma (ENKTL), a biologically aggressive subtype with limited therapeutic options. Among 33 treated patients, the regimen achieved an overall response rate (ORR) of 81.8% and CR rate of 66.7%. With a median follow-up of 20 months, 3-year PFS and OS stood at 51.8% and 72.7%, respectively—remarkably durable for this population. Hematologic toxicities were common but largely manageable. These findings suggest that immunomodulation layered with cytotoxic therapy may meaningfully reshape outcomes in r/r ENKTL.
MRD-Guided Lenalidomide Discontinuation After ASCT in Multiple Myeloma (Abstract 1242O)4
The optimal duration of lenalidomide maintenance after autologous stem-cell transplantation (ASCT) remains undefined. This prospective analysis evaluated discontinuation based on sustained minimal residual disease (MRD) negativity. Fifty-four patients who achieved ≥3 consecutive marrow MRD-negative assessments, negative PET/CT scan and ≥36 months of maintenance therapy stopped lenalidomide. At a median 41.3-month follow-up post-discontinuation, 3-year PFS was 93.9%, and treatment-free survival reached 75.7%. Approximately one-quarter experienced MRD resurgence, but re-treatment with lenalidomide was generally successful. These findings support MRD-adapted de-escalation as a viable strategy to reduce long-term toxicity without compromising disease control.
iPET-NCCN-IPI Risk Stratification Model in DLBCL (Abstract 1243MO)5
A retrospective analysis of 498 diffuse large B-cell lymphoma (DLBCL) patients from three Chinese centres integrated interim PET biomarkers with the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) to enhance prognostication. Total lesion glycolysis (ΔTLG), maximum standardized uptake value (ΔSUVmax), interim abdominal residual disease and interim NCCN-IPI emerged as independent predictors of outcome. The resulting iPET-NCCN-IPI model outperformed traditional Deauville scoring, particularly in clarifying risk among patients with Deauville score 3. This combined clinical-metabolic tool may refine interim decision-making and guide escalation or de-escalation strategies in frontline DLBCL.
Lipo-MIT + Chidamide in R/R PTCL (Phase II Update) (Abstract 1245MO)6
Updated phase II data from this single-arm trial of mitoxantrone hydrochloride liposome plus chidamide in relapsed/refractory peripheral T-cell lymphoma (PTCL) continue to show encouraging activity. Among 28 eligible patients, the ORR was 70.8% with a CR rate of 45.8%. Median PFS was 13.5 months with the median OS not reached at 5.3 months’ follow-up. Haematologic grade 3/4 toxicities were frequent but consistent with the agents’ known profiles. The regimen’s favorable risk–benefit balance supports further development in an area with significant unmet need.
BEXMAB Phase I/II – Bexmarilimab + Azacitidine in HR-MDS (Abstract 1249MO)7
The Clever-1–directed macrophage checkpoint inhibitor bexmarilimab is being evaluated with azacitidine for higher-risk myelodysplastic syndrome (MDS). Early efficacy signals remain robust, with ORRs of 63% in frontline and 76% in relapsed/refractory patients. Translational analyses demonstrated substantial immune activation, including increased HLA-DR expression on monocytes and expansion of BM CD8+ T cells, alongside metabolic reprogramming of blasts. These dual immune-metabolic mechanisms support continued advancement into phase III investigation.
Conclusion
Collectively, the haematology space at ESMO 2025 reinforces the rapid progress in personalized approaches – from bispecific CAR-T innovation and macrophage-directed therapies to MRD-guided treatment duration and advanced prognostic modeling. These developments promise to refine therapeutic pathways and address longstanding resistance and toxicity challenges across haematological malignancies.
References
- European Society of Medical Oncology (ESMO) Congress 2025. CAR T cell resistance in high-grade B-cell lymphoma is dictated by tumor-associated macrophages [Abstract LBA47]. Presented at: ESMO Congress, 17–21 October 2025, Berlin, Germany.
- European Society of Medical Oncology (ESMO) Congress 2025. CD19/CD22 bispecific CAR-T cell therapy for relapsed/refractory large B-cell lymphoma: A prospective, single-arm, single-center, phase II clinical trial [Abstract 1240O]. Presented at: ESMO Congress, 17–21 October 2025, Berlin, Germany.
- European Society of Medical Oncology (ESMO) Congress 2025. Anti-PD-1-antibody (tislelizumab) combined with chidamide, lenalidomide and etoposide for the treatment of refractory/relapsed extranodal natural killer/t cell lymphoma, nasal type (r/r-ENKTL): Preliminary results from a prospective, multicenter, single-arm, phase II trial [Abstract 1241O]. Presented at: ESMO Congress, 17–21 October 2025, Berlin, Germany.
- European Society of Medical Oncology (ESMO) Congress 2025. Sustained marrow and imaging MRD negativity can lead to lenalidomide discontinuation following ASCT in multiple myeloma: Updated results from a prospective cohort study [Abstract 1242O]. Presented at: ESMO Congress, 17–21 October 2025, Berlin, Germany.
- European Society of Medical Oncology (ESMO) Congress 2025. Risk stratification for diffuse large B-cell lymphoma by integrating interim 18F-FDG PET-CT analysis and the NCCN-IPI: A multicentre retrospective study [Abstract 1243MO]. Presented at: ESMO Congress, 17–21 October 2025, Berlin, Germany.
- European Society of Medical Oncology (ESMO) Congress 2025. Combination of Mitoxantrone Hydrochloride Liposome with Chidamide in Patients with Relapsed or Refractory Peripheral T Cell Lymphoma: Updated Results of the Phase II Study [Abstract 1245MO]. Presented at: ESMO Congress, 17–21 October 2025, Berlin, Germany.
- European Society of Medical Oncology (ESMO) Congress 2025. Macrophage reprogrammer bexmarilimab plus azacitidine in myelodysplastic syndrome: PK/PD and biomarker results from the phase I/II BEXMAB study [Abstract 1249MO]. Presented at: ESMO Congress, 17–21 October 2025, Berlin, Germany.
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Cite: Haematological malignancies: ESMO 2025 round-up. touchHAEMATOLOGY. November 19th, 2025
