Leukemia / ASH 12/24/2025

Reviewing ASH 2025 Data for ALL and TP53-Mutated AML or MDS

Senior male professional in a blue suit and glasses, smiling confidently against a gray background, representing expertise in oncology and medical updates. Abhishek Maiti, MD A healthcare professional in a white lab coat smiling, representing expert oncology updates and cancer research insights. Mycal Casey, DO

Key Points

  • Bispecifics like blinatumomab have entered the frontline setting for acute lymphoblastic leukemia (ALL).
  • Chimeric antigen receptor T-cell (CAR-T) therapies are being investigated as components of ALL treatment, though the research is still in its early stages.
  • TP53-mutated acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) remain an unmet need, though alternatives to intensive chemotherapy are promising.

Bispecifics and CAR-T Therapies in ALL

At the 2025 ASH Annual Meeting (ASH 2025), Mycal Casey, DO, of Medstar Health, met with Abhishek Maiti, MD, of MD Anderson Cancer Center, to discuss the evolving treatment paradigm for bispecific antibodies and CAR-T therapies in ALL, as well as the recent data on novel therapies in TP53-mutated AML or MDS.

In ALL, the bispecific antibody blinatumomab has moved into the frontline setting. In Philadelphia chromosome (Ph)-negative ALL, blinatumomab is combined with chemotherapy in younger fit patients, and with inotuzumab ozogamicin in older patients unfit for chemotherapy. For Ph-positive ALL, blinatumomab is combined with tyrosine kinase inhibitors. 

While these approaches have improved outcomes, the potential long-term consequences of foregoing chemotherapy must be examined. Researchers should also study whether certain subgroups may still benefit from some amount of chemotherapy, said Dr. Maiti.

While bispecifics are more readily available, recent data have also described CAR-T therapies as a consolidation treatment or to solidify undetectable minimal residual disease responses. “We just need a little bit more mature data to understand the long-term risks and benefits, and to really answer the question of can CAR-Ts replace chemotherapy maintenance or allogeneic transplant consolidation,” said Dr. Maiti.

Exploring Novel Approaches for TP53-Mutated AML and MDS

ASH 2025 presentations again highlighted the unmet need for effective treatments in TP53-mutated AML and high-risk MDS that improve upon the standard of care of hypomethylating agents (HMA). Actionable data from ASH 2025 included the PARADIGM trial, which evaluated azacitidine and venetoclax against intensive chemotherapy in newly diagnosed AML. Generally, intensive chemotherapy for TP53-mutated disease is not sufficient, as it increases toxicity without improving outcomes, said Dr. Maiti. Lower-intensity treatments, such as HMA-and-venetoclax-based induction, transplant, and HMA-based maintenance, may yield “as good if not better outcomes” due to lower toxicities and greater rates of transplant.