Acute lymphoblastic leukaemia: Immunotherapy impact across the age spectrum

Q: How has the role of CAR-T therapy evolved for older patients with ALL?
One of the major advantages of CAR-T therapy is that patients who would traditionally be excluded from transplant based on age may still tolerate CAR-T. Although the median ages in pivotal trials such as ZUMA-3 and FELIX were in the 40–50-year range, the FELIX study included patients in their 80s, and real-world data suggest that older patients derive similar benefit compared with younger patients. As a result, we are now very comfortable offering CAR-T therapy to older patients who would not be transplant candidates.

Q: Is there a role for CAR-T therapy earlier in the disease course?
There is significant interest in moving CAR-T therapy earlier than frank relapse. In the FELIX trial, an exploratory cohort of patients treated for MRD-positive disease had remarkably favorable event-free and overall survival compared with patients treated at higher disease burden. More recently, small studies have demonstrated encouraging safety and efficacy using CAR-T as definitive consolidation in first remission, including a study from City of Hope that is now expanding into a multi-institutional trial.

Q: Given these advances, how do you view the role of intensive chemotherapy induction today?
The availability of effective immunotherapies has clearly reduced our reliance on intensive chemotherapy induction, particularly in older or unfit patients. While multi-agent chemotherapy remains important in selected younger or fit patients, many regimens are now intentionally designed with reduced-intensity induction strategies that allow for early incorporation of immunotherapy, with the goal of maintaining efficacy while improving tolerability.

Q: What are the current barriers to broader use of CAR-T therapy?
Cost and insurance approval remain major barriers, and the logistical complexity of CAR-T therapy requires extensive institutional resources, including dedicated social workers and cellular therapy coordinators. Vein-to-vein time and product viability—particularly in heavily pretreated patients—also remain significant challenges.

Q: CAR-T research is advancing rapidly. What developments are you most excited about?
I am particularly excited about allogeneic CAR-T therapies, which may address many of the logistical challenges of autologous products, as well as the development of CAR-T therapies targeting novel antigens and T-cell ALL—an area of major unmet need.

Q: What key unanswered questions remain in this space?
Important questions remain regarding the optimal sequencing of CAR-T therapy and allogeneic transplant, including which patients benefit from transplant following CAR-T. The ideal timing of CAR-T after relapse, and whether it should become standard earlier in the disease course, also require further clarification through ongoing clinical trials and real-world datasets such as large collaborative consortia.