Highlights from ASH 2025

New therapies and therapeutic strategies took center stage at this year’s ASH congress (held 6–9 December in Orlando, Florida, USA). Kasia Moscicka, Head of Feasibility and Site ID; Rhonda Critchlow, Head of Specialized Support Services; and Colleen Ring, Associate Director, Feasibility, provide their key takeaways from ASH 2025, and how these will impact our sponsors going into 2026 and beyond.

Over 30,000 participants from more than 100 countries gathered at this year’s ASH congress in Orlando to talk about all things hematology. Hemato-oncology research dominated the agenda, with new data and advances the main talking points – and understanding how these new developments may impact the future of clinical trials is crucial. Read on for our highlights, with a focus on the new therapies changing clinical practice, advances in immunotherapies, and the importance of improving representation in hematology clinical trials.

Practice-changing hematology clinical trial advances

Throughout the congress, there was a clear shift towards precision and immune-based therapies across both malignant and non-malignant hematology. Groundbreaking research included:

  • Identification of a novel DLBCL subtype driven by SASP-mediated immune evasion
  • The need for synergistic use of chemokine, integrin, and JAK inhibitors to mobilize stem cells and reduce GVHD
  • A randomized CLL trial demonstrating fixed-duration, targeted therapy achieved outcomes comparable to continuous treatment (NCT04608318)
  • Phase 2 data showing benefit of azacitidine plus venetoclax versus intensive induction chemotherapy in newly-diagnosed patients with AML (NCT04801797)

Novel agents are not only improving response rates but are also changing durability, sequencing, and QoL outcomes, setting new standards of care. 

katarzyna moscicka profile

Hematology is moving from incremental improvement to paradigm-level change. This year’s ASH congress has truly challenged our old perceptions – time-limited targeted therapies, earlier use of cellular and immune approaches, and genetically informed treatment strategies are no longer aspirational, but achievable.

Kasia Moscicka, Head of Feasibility and Site ID, PSI

New frontiers in immunotherapies in hematology

Earlier immunotherapy treatment of multiple myeloma

In the past four years, six agents for MM have been approved (two CAR T-cell therapies targeting BCMA, and four bispecifics – three targeting BCMA, and one targeting GPR5CD). As progress in immunotherapy for MM continues, new agents are evaluated, and approved therapies are moved to earlier lines of treatment (for example, bispecific antibodies in combination strategies with established agents such as daratumumab).

In CAR T-cell therapies, where evidence that sequencing earlier in the treatment course is beneficial, changes to earlier lines of therapy were also covered:

  • Ide-cel was initially approved in 2021 after ≥4 lines of prior therapy, and following a phase 3 trial in 2024, this was moved to ≥2 lines of prior therapy
  • Cilta-cel was initially approved in 2022 after ≥4 lines of prior therapy, and following a phase 3 trial in 2024, this was changed to ≥1 line of prior therapy

CAR T-cell therapies have revolutionized outcomes for patients with MM – significant improvements in ORR, CR, MRD negativity, and PFS compared with standard of care have been reported, along with recent positive long-term follow-up data. Their efficacy and safety can be influenced by T-cell fitness, so patients receiving treatment sooner may achieve better outcomes; however, toxicity (and non-response to bridging therapy) must be considered.

Earlier use of CAR T-cell therapies across broader populations could strain infrastructure and resources unless these systems continue to evolve at the same pace. MM is rapidly becoming immunotherapy-first, with increasing pressure on traditional regimens.

Innovation in lymphomas

Over the past eight years, the development of new therapies for relapsed/refractory LBCL has significantly increased long-term survival rates (from <15% to 30–40%). At ASH, major directions for improvement were discussed. Expanding the subset of responders through emerging innovations, such as novel antigen targets (to overcome resistance mechanisms), multi-antigen targets (e.g., overcoming CD19/20 downregulation), new and improved constructs (molecular engineering of 5th-generation CAR T-cell therapies), and new (or expanded) indications and combinations.

Optimized manufacturing is expected to improve efficacy, especially when the manufacturing process can be shortened. The first-in-human data for in vivo CAR T-cell therapy presented at ASH could prove disruptive to current autologous CAR T-cell manufacturing models.

Multiple large trials are underway in DLBCL with bispecifics, including some in front-line settings, and in combination with chemotherapy regimens. Patient loss of CD20 expression following bispecific treatment is a known factor contributing to treatment resistance [1], and constructs targeting CD19 showed promising early-phase data at ASH.

Acute leukemias – major advances and remaining challenges

Before the era of immunotherapies, improvements in patient outcomes in acute leukemia were associated with increased dose intensity, broader access to allo-HSCT, the development of targeted therapies, and improvements in supportive care. Immunotherapy overcomes the limitations of traditional treatments (such as poor long-term outcomes in older adults, relapse, and allo-HSCT-associated morbidity).

  • B-ALL
    • Treatment success in B-ALL is connected to consistent expression of CD19 and CD20, and manageable toxicities
    • Inotuzumab ozogamicin, a CD22-directed ADC, demonstrated superior response rates and survival in the INO-VATE trial, but is associated with myeloid and liver toxicity. Potential front-line use with low-dose chemotherapy in older patients appears promising; in younger patients, dose optimization to avoid toxicity is recommended
    • Blinatumomab, a bispecific T-cell engager targeting CD19, is the first agent specifically approved for MRD-positive B-ALL, with efficacy demonstrated in various patient groups (including over chemotherapy in young populations). Although it has a manageable safety profile, adding blinatumomab to intensive chemotherapy regimens may increase infectious complications
    • Combination approaches were shown to improve outcomes in younger patients, with promising results in older patients without the added burden of chemotherapy. Frontline strategies now frequently integrate inotuzumab ozogamicin and blinatumomab, focusing on managing MRD and adapting to the patient’s health status
    • CAR T-cell therapies (generally targeting CD19, though with varying constructs and safety profiles) have strong ORR rates and long-term survival data. High tumor burden, inadequate CNS protection, resistant cytogenetics, low CD22 expression, and prior therapy failures are indicative of potential lack of response; further research is warranted on treatment strategies and integration with more traditional therapies
  • T-ALL
    • The absence of a universal target still proves to be the biggest challenge in T-ALL – the majority of evidence points towards CD38 (highly expressed, and mAbs targeting CD38 have safely been combined with chemotherapy)
    • CAR T-cell therapy in T-ALL faces multiple challenges, including self-killing, T-cell aplasia, leukemic contamination, and antigen masking. Various promising approaches to overcome these difficulties were highlighted at ASH, including gene disruption and using allogenic CAR T-cells
  • AML
    • AML remains the most challenging – lacking a universal target (despite attempts with CD33, CD123, FLT3, and others). Limited activity or unacceptable toxicity, of investigative therapies has proven difficult to overcome in the past few years
    • Changing our view of AML to a genetically stratified disease may help improve the development of new therapies, and also address real-world outcomes and access disparity
    • Current research prioritizes reducing toxicity and overcoming the immunosuppressive AML microenvironment – over 100 CAR T-cell therapy trials are ongoing, exploring antigen targeting and safety improvements

While research into AML is still underrepresented among the three main acute leukemias, we expect that chemotherapy de-escalation in favor of immunotherapies, with novel targets, combinatorial approaches, and optimized sequencing for antibody and cell therapies, will continue to revolutionize treatment paradigms for the coming years.

Rhonda Critchlow, Head of Specialized Support Services, PSI

Beyond CAR T-cells

Novel immunotherapy strategies were also a recurring theme at ASH. Emerging platforms and strategies included:

  • TCR T-cell therapy: Harnessing T-cells to recognize and target mutations in tumor growth proteins on HLA molecules
  • In vivo engineering strategies: Enhancing CD4 T-cell reconstitution post-transplant to improve patient outcomes
  • NK cell-based platforms: Novel bispecific engagers with cytokine-induced memory-like NK cells targeting CD38 in MM promise a non-toxic alternative, with further applications in autoimmune disorders
  • iPSC-derived mesenchymal stem cells: Targeting the tumor microenvironment is a hot topic throughout all of oncology – iPSC MSCs can alter tumor microenvironments, enhancing the effectiveness of immunotherapies in challenging patients and circumstances
  • Bacterial immune engagers: Delivering cancer immunotherapy directly to tumors, using the bacterium’s natural ability to target hypoxic, tumor-rich areas

Scalability, access, and health system readiness are the metrics with which the next wave of innovation will be judged. Solutions to cost, logistics, and global accessibility barriers are just as important as clinical efficacy in ensuring patients receive the best care possible.

Colleen Ring, Associate Director, Feasibility, PSI

Diversity representative of epidemiology

Changing perceptions in hematology

Diversity is crucial in clinical trials and throughout healthcare – trial enrollment should be reflective of the epidemiology of the disease, mirroring the population impacted. Adapting the patient and healthcare team’s perception of care to include clinical trial participation remains a significant barrier. ASH and the congress participants are taking great strides to improve engagement and access.

  • A roadmap to integrate diversity, equity, and inclusion in hematology clinical trials, developed by ASH, set the stage [2]
    • – Key issues include harmonization of demographic terminology, engagement of patients across the entirety of the trial, a more prominent role for IRBs (local IRBs understand community needs and dynamics), broadening trial monitoring processes and accessibility (for example, remote visits), and improvements in trial design (such as broadening of eligibility criteria, or decentralized designs)
  • Community clinicians are encouraged to become investigators in clinical trials. This creative, decentralized approach would help engage motivated clinicians and provide a competitive advantage (both research and financial) for their practice, and would improve the diversity of trial participants

Sponsors could support community physician participation through a ‘hub and spoke’ model with academic centers. Appropriate budgeting (e.g., adequate reimbursement to offset research-related deficits versus more profitable patient care; funding improved infrastructure to improve patient equity), training, and communication are needed.

  • It is vital for CROs to engage with community-based hematologists to improve planning, representation, and enrollment

Overcoming access gaps

Findings from an analysis of Medicare data suggested that if the distance from the patient’s home to the nearest academic transplant center was under 50 km, the likelihood of a patient receiving CAR T-cell therapy increased by 40% [3]. More centers capable of delivering CAR T-cell therapy are needed.

We have made significant progress in managing safety and toxicity, and the use of steroids and IL-6 blockade has improved the ability to deliver CAR T-cell therapy, expanding the patient pool and improving access. Bridging therapies may be administered by local providers, and some academic centers have developed roadmaps to help referring physician colleagues in community centers improve access to treatment.

In summary

ASH continues to set the global clinical and scientific hematology agenda. Immunotherapy and gene therapy are reshaping standards of care, significantly improving patient outcomes and transforming the clinical trial landscape. Earlier-line use of novel agents is accelerating, particularly in MM. Ensuring that the industry facilitating these groundbreaking clinical trials can meet increased demands is crucial, as is considering access, scalability, and equity in protocol design.

It is vital to partner with a CRO that knows how these advances in care will affect your hematology clinical trial, so you deliver it on time and on budget.

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References

1. Schuster, S.J., et al., Loss of CD20 expression as a mechanism of resistance to mosunetuzumab in relapsed/refractory B-cell lymphomas. Blood, 2024. 143(9): p. 822–832.
2.Kuaban, A., et al., The roadmap to integrate diversity, equity, and inclusion in hematology clinical trials: an American Society of Hematology initiative. Blood Adv, 2025. 9(4): p. 687–695.
3.Chung, A.P., et al., Inequalities in CAR T-cell therapy access for US patients with relapsed/refractory DLBCL: a SEER-Medicare data analysis. Blood Adv, 2025. 9(18): p. 4727–4735.