The American Society of Hematology (ASH) held its 67th Annual Meeting from 6–9th December 2025. The six selected late-breaking abstracts showcase cutting-edge alternatives to conventional CAR-T therapy, refined strategies in immune disorders, landmark head-to-head trials in CLL/SLL, genomics and pragmatic perioperative care. Below, touchHAEMATOLOGY breaks down all six late-breaking abstracts, highlighting the key data, take-home messages and the insights that matter most for clinical practice.
inMMyCAR (LBA-1)
Prof Phoebe Joy Ho (University of Sydney, Camperdown, New South Wales, Australia)
In a first-in-human phase I study, KLN-1010 offers an alternative to conventional CAR-T therapy: a single intravenous administration sufficing to generate fully human anti-BCMA CAR-T cells in vivo, circumventing the need for apheresis, ex-vivo manufacturing or lymphodepleting chemotherapy. In the initial cohort (three patients, aged 61–72, each with 3–4 prior therapies), the therapy was delivered 13–18 days after consent. Within one month all three patients achieved measurable-residual-disease (MRD) negativity (sensitivity 10⁻⁵ or 10⁻⁶), and by month 3 one patient remained MRD-negative (10⁻⁶). Simultaneously, all achieved a partial response at month 1 which deepened to a very good partial response (VGPR) by month 3; none had disease progression at last follow-up. Two patients had infusion-related reactions, two developed Grade 2 cytokine release syndrome and cytopenias were transient. These initial data suggest that in-vivo CAR-T generation is biologically active and capable of inducing early MRD-negative responses without the logistic burden of conventional CAR-T. The study remains ongoing.
VAYHIT2 (LBA-2)
Dr Hanny Al-Samkari (Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA)
In patients with primary immune thrombocytopenia (ITP) failing first-line corticosteroids, the combination of ianalumab (an anti–BAFF-receptor antibody) with eltrombopag was tested in the randomized, double-blind, placebo-controlled phase III VAYHIT2 trial. Adults received four monthly IV infusions of ianalumab (9 mg/kg or 3 mg/kg) or placebo, alongside daily eltrombopag for 16 weeks followed by an 8-week taper. Of 152 enrolled, 50 received 9 mg/kg, 51 received 3 mg/kg, and 51 placebo. Over median follow-up of 11.6–13.6 months, both doses significantly prolonged time to treatment failure (TTF) compared with placebo (hazard ratios 0.55 [95% CI 0.32–0.92], p=0.021 and 0.58 [95% CI 0.34–0.98], p=0.023), versus a median TTF of 4.7 months in placebo. Moreover, at 6 months a sustained response (SR6) was achieved in 62.0% of patients at 9 mg/kg (versus 39.2% for placebo; CMH p=0.023). Importantly, ianalumab was well tolerated: grade ≥3 adverse events occurred in 24.0% (9 mg/kg), 20.0% (3 mg/kg) and 3.9% (placebo), and the frequency and severity of infections – including grade ≥3 – were similar across arms. These results demonstrate that a short course of ianalumab plus eltrombopag induces durable responses in ITP. Longer-term follow-up, which is ongoing, will confirm whether administration of ianalumab early in the disease course is ultimately-disease-modifying in ITP.
Pirtobrutinib versus bendamustine–rituximab in frontline CLL/SLL (LBA-3)
Prof Wojciech Jurczak (Maria Sklodowska-Curie National Research Institute of Oncology, Kraków, Poland)
The phase III randomized trial comparing pirtobrutinib – a non-covalent Bruton’s tyrosine kinase (BTK) inhibitor – to bendamustine plus rituximab (BR) marks a landmark head-to-head in previously untreated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). By directly contrasting pirtobrutinib with a longstanding chemoimmunotherapy standard in frontline disease, the study offers clarity on relative efficacy, tolerability and long-term value. While the abstract presents multiple efficacy endpoints (response rates, progression-free survival [PFS], hazard ratios) and safety data, I encourage direct consultation of the published results for exact numbers. The data provide direct evidence supporting pirtobrutinib as a viable frontline option, potentially sparing patients from the toxicities of chemotherapy, but its full place in therapy depends on a number of factors including patient comorbidities, long-term data and financial implications.
IBMDx (LBA-4)
Dr Lucy Fox (Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia)
Inherited bone marrow failure syndromes (IBMFS) can be genetically complex and sometimes evade diagnosis by standard targeted panel or whole-exome sequencing. The IBMDx study evaluated upfront whole genome transcriptome sequencing (WGTS) in patients with suspected IBMFS, thus capturing not only coding but also structural or regulatory genomic abnormalities. The data revealed germline genomic diagnoses in a number of cases – including novel genomic abnormalities not previously associated with IBMFS – expanding the genetic spectrum of such disorders. By broadening detection beyond the limitations of conventional DNA-based panels, WGTS may substantially increase diagnostic yield. This has important implications for genetic counselling, donor selection, surveillance and management.
TRACTION (LBA-5)
Dr Brett Houston (University of Manitoba/CancerCare Manitoba, Winnipeg, Manitoba, Canada)
Bleeding remains a major driver of perioperative transfusions, morbidity and resource use. The TRACTION trial examined whether implementing a hospital-wide policy of prophylactic tranexamic acid (TXA) in major non-cardiac surgeries would reduce transfusion rates. As a pragmatic, policy-level intervention, the study evaluates translation of TXA’s known haemostatic benefits into real-world institutional practice. The abstract reports transfusion rates, effect sizes and safety outcomes (including thrombotic events) – critical data for assessing whether routine TXA policy is defensible and scalable. Such findings could influence surgical transfusion protocols worldwide – though adoption should await full review of the exact numbers and follow-up, especially for safety events.
MajesTEC-3 (LBA-6)
Dr María-Victoria Mateos (University of Salamanca, Spain)
In the relapsed/refractory multiple myeloma (RRMM) setting, combining the BCMA-targeted bispecific antibody teclistamab with daratumumab (anti-CD38) offers a potentially chemotherapy-free immunotherapy regimen. The phase III MajesTEC-3 trial randomized patients to teclistamab + daratumumab versus investigator choice of daratumumab with dexamethasone plus either pomalidomide (DPd) or bortezomib (DVd). The abstract reports detailed outcome data – response rates, progression-free survival (PFS), safety profiles including adverse events – which should be reviewed for precise numbers. By directly comparing a bispecific-based regimen against familiar daratumumab-triplet backbones, these results may influence how clinicians select salvage therapy in RRMM, weighing efficacy, tolerability, and convenience.
Conclusion
Across these six late-breaking abstracts, ASH25 highlighted both therapeutic and diagnostic progress. Early in-vivo CAR-T data demonstrated the feasibility of generating anti-BCMA CAR-T cells without lymphodepletion, while VAYHIT2 suggested ianalumab may offer more durable disease control when added early in ITP. Frontline pirtobrutinib provided a chemotherapy-free comparator to BR, and WGTS expanded diagnostic yield in inherited marrow failure. Meanwhile, TRACTION evaluated TXA policy change at scale, and MajesTEC-3 compared a bispecific-based regimen against established daratumumab triplets. Together, these abstracts showcase fresh, innovative research, potential practice shifts and early signals that we will all want to follow closely.
Disclosure: This article was created independently by the touchHAEMATOLOGY team utilizing AI as an editorial tool (ChatGPT (GPT-4o) [Large language model]. https://chat.openai.com/chat.) The content was developed and edited by human editors. No funding was received in the publication of this article. It is not affiliated with the American Society of Hematology (ASH).
Cite: ASH25: Discover the late-breaking abstracts. touchHAEMATOLOGY. December 11th, 2025
Related content
- Countdown to #ASH25!
- CAR-T therapy: A new era for lymphoma
- ASH25: Top abstracts in non-malignant haematology
SIGN UP to touchHAEMATOLOGY!
Join our global community today for access to thousands of peer-reviewed articles, expert insights, and learn-on-the-go education across 150+ specialties, plus concise email updates and newsletters so you never miss out.
