Key Clinical Summary:

• Design/Population: At ASH 2025, emerging clinical trial data were reviewed in acute lymphoblastic leukemia (ALL), spanning earlier-line CAR T-cell strategies, novel CAR targets beyond CD19, and frontline therapy optimization in Philadelphia chromosome-positive (Ph+) ALL.
• Key Outcomes: Studies demonstrated CD19 CAR T-cell therapy used as consolidation in ALL patients ineligible for transplant, showing feasibility of moving CAR T earlier in treatment. Phase 1 trials of non-CD19 CAR T-cells showed activity in patients with CD19-negative relapse. In Ph+ ALL, a phase 3 study incorporating ponatinib upfront achieved deep molecular remissions, raising the possibility of transplant omission in select patients.
• Clinical Relevance: These findings highlight a shift toward earlier, more personalized use of CAR T-cell therapy and targeted TKIs in ALL, potentially reducing reliance on allogeneic transplant and expanding effective options for high-risk and antigen-escape populations.

Matthew Connor, MD, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, highlighted several advances in the treatment of acute lymphoblastic leukemia (ALL) presented at the 2025 American Society of Hematology (ASH) Annual Meeting & Exposition in Orlando, Florida.

He discussed studies moving CD19 CAR T-cell therapy into earlier lines as consolidation for patients ineligible for transplant, as well as promising phase 1 data on CAR T therapies targeting non-CD19 antigens for patients with CD19-negative relapse. Additionally, he discussed phase 3 results in Philadelphia chromosome–positive ALL showing that ponatinib-based frontline therapy may achieve deep remissions.

Transcript:

My name's Matt Connor. I'm an assistant professor at the University of Pennsylvania. I'm here at ASH 2025. I treat patients with leukemia and with CAR T-cell therapy as well.

There have been some really exciting abstracts at this ASH meeting, particularly with regard to ALL. A couple of nice CAR-T studies. One, looking from the City of Hope Group, looking at CAR T-cells, CD19 CAR T-cells for ALL patients as consolidation therapy. Exciting to see this very effective therapy for relapsed or refractory disease being brought into earlier lines of treatment for patients who might not be eligible for other consolidative therapies such as transplant.

In addition, seeing some encouraging phase 1 data from CAR T-cells targeting other antigens aside from CD19 for the subset of patients with ALL who relapse without CD19-positivity.

Then aside from CAR T-cells, seeing some interesting and promising data in the Philadelphia chromosome-positive disease space from the Italian group looking at phase 3 study of ponatinib as part of initial therapy in patients in achieving deep remissions and possibly being able to forego transplant in this previously thought of high-risk patient subset.

Source:

Aldoss I, Wang X, Zhang J, et al. CD19-CAR T cell therapy as a denitive consolidation in older adults with b-ALL in CR1 is safe and induces durable MRD- remission. Dec 6-9, 2025; Orlando, FL. Abstract: 443

Aldoss I, Wang X, Chen L, et al. BAFFR-CAR T cells (PMB-CT01) show promising safety and anti-leukemia efficacy in relapsed/refractory B-cell ALL patients after CD19-targeted therapy failure, including CD19-negative disease. Dec 6-9, 2025; Orlando, FL. Abstract: 813

Chiaretti S, Di Trani M, Skert C, et al. First results of the Phase III GIMEMA ALL2820 trial comparing ponatinib plus blinatumomab to imatinib and chemotherapy for newly diagnosed adult ph+ acute lymphoblastic leukemia patients. Dec 6-9, 2025; Orlando, FL. Abstract: 439