The following summaries highlight key findings from research posters presented at the 67th ASH Annual Meeting, showcasing new developments in oral maintenance therapies for acute myeloid leukemia (ALL).

All abstracts can be accessed here –> Abstracts ASH 2025

Selected abstracts –> Selected abstracts ALL

Advances in treatment for B–cell acute lymphoblastic leukemia (B‑ALL)

How treatment for adults with B-ALL is changing¹

For many years, the main treatment for adults with B-ALL has been intensive chemotherapy, often given in many cycles over several years. This treatment was especially challenging for older adults, who are more likely to have other health problems and to experience serious side effects from intensive chemotherapy.

Treatment for B‑ALL is evolving. Doctors are increasingly using newer types of medicines to reduce how much chemotherapy some patients need, while still aiming to control leukemia for the long term.

One group of these newer treatments is immunotherapy.  These treatments help strengthen the body’s own immune system to better recognize and fight leukemia cells. Some immunotherapies use antibodies that connect to leukemia cells and either guide immune cells to attack them or deliver treatment directly to the leukemia.

Ph-positive (Ph+) B-ALL in adults^1,2

Philadelphia chromosome–positive (Ph‑positive) B‑ALL is different from Ph‑negative disease because the leukemia cells have a specific genetic change that forms the Philadelphia chromosome. This change creates an overactive protein (BCR-ABL) that tells the cancer cells to grow out of control. This specific genetic change can be targeted with certain medicines, unlike Ph-negative (Ph-) disease. Tyrosine kinase inhibitors (TKIs), such as dasatinib or ponatinib, are a type of targeted drug that specifically block the BCR-ABL protein, stopping the signals that make cancer cells grow and spread.

In the past, Ph+ B‑ALL had poor outcomes with chemotherapy alone, but now doctors combine TKIs with immunotherapies to reduce chemotherapy use. Examples of immunotherapies that use antibodies include blinatumomab, which guides the immune system to attack leukemia, and inotuzumab, which delivers anti-cancer treatment directly into cancer cells. CAR T immunotherapy, which modifies the patient’s own immune cells, is also being explored to kill any remaining cancer cells following treatment to delay or prevent relapse.

Promising results from clinical trials in Ph+ B-ALL^1,2–6

Several clinical trials are exploring chemotherapy-free treatment regimens in adults with Ph+ B-ALL. They tested regimens that combined a TKI (dasatinib or ponatinib) with the immunotherapy, blinatumomab. Results have shown high success rates, with many older adults reaching deep remission, with undetectable leukemia. This has reduced the need for a stem cell transplant right after first remission, avoiding risks like infections or graft-versus-host disease. For the first time, long-term survival and the possibility of cure are being seen in many older adults with Ph+ B-ALL.

Removing chemotherapy from the treatment regimen has coincided with emergence of cancer relapse in the central nervous system (CNS). As such, researchers are reconsidering strategies to manage this appropriately.

Ph-negative B-ALL in older adults¹

Unlike Ph‑positive B‑ALL, which has the Philadelphia chromosome and can be treated with targeted therapies like TKIs, Ph- B‑ALL lacks this genetic abnormality. As a result, it can be the hardest subtype to treat, especially in older adults.

In the past, intensive chemotherapy alone caused more harm than good in adults with Ph- B-ALL. These patients would often face low survival rates, frequent relapses, and early deaths.

Promising results from clinical trials in Ph- B-ALL^1,7,8

Researchers are now testing lower intensity ‘chemoimmunotherapy’, where antibodies like blinatumomab are added to much smaller amounts of traditional chemotherapy.  Fully chemotherapy-free regimens, such as inotuzumab followed by blinatumomab, are also being explored. These new approaches have greatly improved results for older adults. 1-year survival without the leukemia coming back has greatly improved. Approximately 75% of older adults on a chemotherapy-free regimen stayed free of relapse, progression or death for up to a year, much better than the 30% seen in older studies.

Despite the improved survival rates, toxicity remains a concern even with lower-intensity chemotherapy. Clinical trials that are exploring these new approaches are still ongoing and there is still no standard approach established for older patients.

CAR T-cell therapy is where a patient’s T cells are collected, modified in a lab to better attack leukemia, and reinfused. This approach is being explored as a consolidation step to deepen and maintain remission in older adults who respond to initial therapy. Early data shows it is well-tolerated and leads to durable undetectable leukemia, but it is still experimental and not a standard treatment.

Challenges of reducing chemotherapy in B-ALL^9–11

Using less chemotherapy can have real benefits. It can mean fewer days in hospital and a lower risk of long-term side effects. But it can also create new challenges.

In B-ALL, leukemia cells can sometimes hide in certain parts of the body. These are called sanctuary sites. The most important sanctuary site is the brain and CNS. Less commonly, leukemia can also affect areas such as the eyes, skin, bones, or other organs. These areas are harder to treat for more than one reason. Some medicines do not reach them as easily. In addition, the environment in these parts of the body can protect leukemia cells and make treatments less effective.

Traditional chemotherapy plays a key role in protecting these areas, particularly the CNS. When chemotherapy is reduced, there is a small risk that leukemia could return in these sites even if the bone marrow remains in remission. Relapse outside the bone marrow is uncommon, especially with standard chemotherapy-based treatment.

As lower-chemotherapy and chemotherapy-free approaches are used more widely, doctors are paying closer attention to how best protect the CNS. In some cases, treatment plans are adjusted by keeping a small amount of chemotherapy or targeted CNS treatment to reduce this risk. ​

What does this mean for people with B-ALL?^1,9

New immunotherapies have made it possible to reduce chemotherapy in ways that were not possible in the past. The type of treatment will depend on your age, overall health, and specific leukemia features, such as the Philadelphia chromosome or other potential gene mutations.

For most people with B-ALL, relapses in the brain or CNS are uncommon. However, research shows that newer treatments that reduce or remove chemotherapy may not fully protect the CNS in every patient. That’s why doctors may still need to include treatments specifically aimed at protecting the brain and CNS.

This careful balance aims to keep cure rates high while lowering long-term side effects as much as possible. Treatment plans are tailored to each person, based on their individual risk factors and ongoing response to therapy.

Can chemotherapy be reduced in children, adolescents and young adults with
B-ALL?¹²

Children with B-ALL already have very high cure rates. Because of this success, a major focus of current research is not just curing the disease but reducing the long-term health problems caused by intensive chemotherapy.

These long-term effects can include heart disease, fertility problems, bone health issues, metabolic conditions, and ongoing psychological or social challenges. For adolescents and young adults, these effects can have lifelong consequences.

The key challenge is how to safely reduce the intensity or length of chemotherapy while keeping cure rates high.

 What are researchers testing? ^12–14

The aim is not to stop chemotherapy altogether. The focus is on reducing or shortening the most toxic parts of treatment. Recent studies are exploring whether immunotherapies, such as blinatumomab or inotuzumab, can be used alongside chemotherapy to reduce how much chemotherapy is needed.

So far, most trials have added immunotherapy on top of existing chemotherapy, rather than replacing parts of chemotherapy altogether. This approach has shown encouraging results, particularly in adolescents and young adults. However, it can also increase treatment complexity and carries its own risks, including infections.

At present, strategies that fully replace chemotherapy with immunotherapy are still being tested and need confirmation in larger, randomized clinical trials before they can be widely adopted.

Which children may benefit most? ^10,15

Current clinical trials mainly focus on children with standard-risk or favorable-risk B-ALL, where cure rates are already very high with standard chemotherapy.  As these children respond well to chemotherapy and have strong prognoses, it could be argued that they may be more suitable candidates for chemotherapy removal or reduction. Alternatively, children who are less chemotherapy-sensitive already experience limited benefit, in which case removing or reducing chemotherapy may be a reasonable approach.

Children at the lowest risk of CNS relapse may also be good candidates for reducing chemotherapy, especially if CNS-active chemotherapy drugs are being considered for removal. The challenge for doctors is how to reliably identify children at high or low risk of CNS relapse.

Children with Ph+ B-ALL, who may already have targeted treatment options available, such as TKIs, could be suitable candidates for replacing or reducing chemotherapy.

Children with Down syndrome and B-ALL suffer from higher relapse rates and toxicity, and may also benefit from less intensive treatments.

Importantly, reducing chemotherapy is not suitable for every child with B-ALL. Careful testing and risk assessment are essential to make sure no one gets undertreated or overtreated.

Why is this especially relevant for adolescents and young adults? ¹

Adolescents and young adults are ideal candidates for chemotherapy reduction, as they often struggle with long treatment phases, therefore shorter targeted regimens may improve adherence. Like children, long-term side effects from intensive chemotherapy are also a major concern.

Studies in this age group suggest that reducing chemotherapy exposure may be possible for some patients, particularly using immunotherapy such as blinatumomab. However, careful assessment of treatment responses, risks of relapse and results of clinical trials is essential to avoid undertreatment or overtreatment.

Ongoing research and challenges¹²

Ongoing international studies are testing whether chemotherapy can be safely reduced or replaced in certain phases of treatment protocols. The primary goal is to keep cure rates high while improving the quality of life of patients, both on treatment and off treatment.

However, these trials need longer follow-up time to fully understand all long-term benefits and risks of reducing or replacing chemotherapy.

What does this mean for children, adolescents, and their families? ¹²

Reducing chemotherapy has the potential to protect children from lifelong health problems while still curing their cancer. Immunotherapy has made this goal more realistic than ever before.

However, deciding which treatments to reduce or replace and for which children must be done carefully. These questions are being addressed through carefully designed clinical trials. As research progresses, the experiences and priorities of patients and families, including which side effects are most difficult to live with, are expected to play an important role in shaping future treatment approaches.

References

1. O’Dwyer K. Presentation at the ASH Annual Meeting, Orlando, December 2025.
2. Patel A, et al. Blood. 2025;146(Suppl 1):441.
3. Foa R, et al. J Clin Oncol. 2023;42:881–885.
4. Advani A et al. Blood Adv. 2023;7:1279–1285.
5. Kantarjian H et al. J Clin Oncol. 2024;24:4246–4251.
6. Chiaretti S, et al. Blood. 2025;146(Suppl 1):439.
7. Wieduwilt MJ, et al. J Clin Oncol. 2025;43(32):3526-3535.
8. Aldoss I, et al. 2025;146(Suppl 1):443.
9. Cassaday R. Presentation at the ASH Annual Meeting, Orlando, December 2025.
10. Fielding AK, et al. 2007;109:944–950.
11. Short NJ, et al. J Hematol Oncol. 2025;18:55.
12. Gupta S. Presentation at the ASH Annual Meeting, Orlando, December 2025.
13. Hodder A, et al. J Clin Oncol. 2024;42(8):907–914.
14. O’Brien MM, et al. J Clin Oncol. 2022;40(9):956–967.
15. Rabin KR, et al. J Clin Oncol. 2024;42(2):218–227.

Chemotherapy‑free ponatinib plus blinatumomab regimen for adults with Ph+ B‑ALL¹

1. Chiaretti S, et al. Blood. 2025;146(Suppl 1):439.

What was the study about?

This phase III study looked at whether adults newly diagnosed with Philadelphia chromosome–positive B-cell acute lymphoblastic leukemia (Ph+ B‑ALL) could be treated effectively without chemotherapy. As such, a chemotherapy-free approach was tested that combined a tyrosine kinase inhibitor (TKI) called ponatinib and an immunotherapy drug called blinatumomab. TKIs are targeted drugs that block signals that make cancer cells grow and spread. Immunotherapy treatments help strengthen the body’s own immune system to better recognize and fight leukemia cells.

This new approach was compared directly with the current standard treatment, which combines a different targeted TKI (imatinib) with chemotherapy. Participants received either ponatinib for the first 70 days, followed by ponatinib + blinatumomab, or they received concomitant imatinib + chemotherapy for the duration of the trial.

Who took part?

• 236 adults with Ph+ B‑ALL

• People were randomly split between the two treatments
  • 158 received the chemotherapy-free regimen of ponatinib plus blinatumomab, average age 57 years
  • 78 received imatinib plus chemotherapy, average age 55 years

Key results

• Complete hematological remission: By Day 70, 94% of people on the chemotherapy-free regimen achieved remission (defined as less than 5% leukemia cells in their bone marrow) compared with 79% on standard chemotherapy. Reducing the number of leukemia cells allows the bone marrow to resume producing healthy blood cells
• Complete molecular remission: After the first 70 days of treatment, very sensitive tests that look for tiny amounts of remaining leukemia showed similar results in both groups, with no detectable leukemia in 47% of people on chemotherapy-free treatment and 44% on standard chemotherapy. However, by day 133, significantly more people on chemotherapy‑free treatment had no detectable leukemia compared with the chemotherapy regimen (70% vs 53%). No detectable leukemia can mean a lower chance of experiencing relapse
• Event‑free survival: 90% of people on the chemotherapy-free regimen were still alive without experiencing relapse or progression after 2 years of follow‑up compared with 74% on standard chemotherapy
• Overall survival: At 2 years of follow-up, 94% of people on the chemotherapy-free regimen were still alive, compared with 77% on standard chemotherapy arm

Key safety information

• The most common side effects were low blood counts, infections, and problems with the digestive system or liver, which can be expected with these treatments
• With the chemotherapy-free treatment, serious side effects occurred but were associated with fewer treatment‑related deaths than standard chemotherapy

What does this study mean for people with Ph+ B‑ALL?

These results suggest that a chemotherapy‑free combination of ponatinib and blinatumomab could become a new standard treatment option for adults with Ph+ B‑ALL. The chemotherapy-free combination offers deep, long‑lasting remissions where leukemia drops to very low or undetectable levels and stays controlled. This means higher survival rates than traditional chemotherapy-based treatments, and lower chance of relapse.

Key highlights

Overall Clinical Insights

1. Immunotherapy (blinatumomab, Inotuzumab ozogamicin, CAR-T) is central in relapsed/refractory and high-risk ALL across age groups.
2. Targeted therapies (TKIs, FLT3 inhibitors, venetoclax) improve outcomes in molecularly defined subgroups.
3. MRD-directed strategies optimize therapy intensity, transplantation decisions, and maintenance approaches.
4. Pediatric and adult therapies are converging, with risk-adapted regimens and novel agents improving long-term survival.
5. Post-transplant maintenance and second HCT provide options for high-risk or relapsed patients.

Blinatumomab and Inotuzumab Ozogamicin

• Blinatumomab rechallenge: Safe and effective in adolescents, young adults, and adults with relapsed/refractory B-ALL.
• Frontline blinatumomab: Reduces the impact of traditional adverse prognostic factors in standard-risk pediatric B-ALL (COG AALL1731).
• Blinatumomab vs high-dose chemo in children: Effective first-line therapy in high-risk pediatric B-ALL (cALL-pol trial).
• Inotuzumab ozogamicin: Effective in frontline combinations (with vincristine/prednisone or hyper-CVAD) and as a bridge to CAR-T therapy.

Clinical Implications:

• Blinatumomab and Inotuzumab ozogamicin can improve remission rates in high-risk or relapsed/refractory B-ALL.
• Sequential or combined strategies optimize outcomes, especially for older adults or pediatric patients unfit for intensive chemo.

CAR T-Cell Therapy

• CD19 CAR-T: Effective as frontline consolidation in adults and for CNS relapse in pediatric B-ALL.
• Sequential CD19/CD22 CAR-T: Promising for relapsed/refractory B-ALL.
• Universal and armored CAR-T (CD7, IL18-armored, BAFFR-CAR, Orca-T): Active in T-ALL or B-ALL after prior CAR-T failure.
• Brexucabtagene autoleucel (Brexucel): Effective as post-HCVAD/INO/blinatumomab consolidation, with real-world post-CAR-T transplantation improving relapse-free survival.

Clinical Implications:

• CAR-T therapy is now central for relapsed/refractory B-ALL, including high-risk and CNS-involved disease.
• Universal and armored CAR-Ts expand options for patients with prior CAR-T exposure or T-ALL.
• Post-CAR-T HCT may consolidate remission in high-risk patients.

Tyrosine Kinase Inhibitors in Ph+ B-ALL

• Ponatinib + blinatumomab: Superior molecular responses in newly diagnosed adult Ph+ B-ALL (GIMEMA ALL2820, EWALL PH03).
• Asciminib: Shows real-world activity in relapsed/refractory Ph+ B-ALL and lymphoid blast crisis of CML.
• Olverembatinib + low-intensity chemo: Effective in newly diagnosed Ph+ ALL (POLARIS-1).

Clinical Implications:

• TKI + immunotherapy (blinatumomab) is emerging as the standard of care for adult Ph+ B-ALL.
• New TKIs (asciminib, olverembatinib) are options for relapsed/refractory disease.

Venetoclax-Based Therapy

• R/R B-ALL and ETP-ALL: Venetoclax combinations (with INO, dexamethasone, azacitidine) show efficacy in heavily pretreated patients.
• Maintenance post-HCT: Venetoclax + azacitidine shows potential to reduce relapse.
• Adult T-ALL: HDAC inhibitor + venetoclax + azacitidine demonstrates safety and early efficacy.

Clinical Implications:

• Venetoclax expands salvage therapy options for high-risk and relapsed B- and T-ALL.
• Maintenance therapy post-HCT may prolong remission in high-risk populations.

Measurable Residual Disease (MRD) & Risk Stratification

• Early MRD assessment: Improves treatment outcomes in low-risk pediatric ALL (TPOG-ALL study).
• NGS-MRD negative patients: Achieve high EFS and OS post-allogeneic HCT (EndRAD trial).
• Predictors of relapse: MRD-guided interventions, frontline blinatumomab, and post-transplant strategies are critical.

Clinical Implications:

• MRD-directed therapy should guide both pediatric and adult ALL management.
• Risk-adapted approaches (MRD, genetic markers) improve outcomes and reduce overtreatment.

Allogeneic Hematopoietic Stem Cell Transplantation (HCT)

• Second HCT: Viable option for post-transplant relapse in the era of targeted therapy.
• Conditioning intensity: Non-TBI conditioning or reduced-intensity regimens can yield high survival, especially in MRD-negative patients.
• Donor type: Comparable outcomes for haploidentical, sibling, and unrelated donors in T-ALL.
• Low-dose chidamide post-HCT: Safe maintenance in T-ALL or lymphoma.

Clinical Implications:

• HCT remains critical in high-risk or relapsed ALL.
• MRD status should guide transplant intensity and post-transplant maintenance.

Pediatric ALL Insights

• PAX5r ALL: Poor prognosis; FLT3 inhibition is a potential novel therapy.
• T-ALL outcomes: Contemporary protocols improve pediatric outcomes (DFCI ALL consortium).
• DNA methylation markers at birth: Can predict future ALL development.

Clinical Implications:

• Genetic and molecular profiling is crucial in pediatric ALL for risk stratification and therapy selection.
• Novel targeted agents (FLT3 inhibitors) could improve outcomes in genetically high-risk pediatric ALL.

Additional data published

Inotuzumab Ozogamicin: ASH 2025_ALL Pfizer

Venetoclax in Combination with Multiagent Cytotoxic Chemotherapy: ASH 2025_ALL Servier