ALL is mainly classified into B-cell and T-cell ALL. It can occur at any age but is more common in young children (0–14 years) and it develops quickly, so people are usually unwell for only a short period before they are diagnosed. In the treatment outlook, CAR-T cells provide a long-term benefit with a one-time treatment, avoiding the toxicity of salvage chemotherapy and autologous transplant for patients with high-risk illnesses. The approvals have altered the standard of care for high-risk patients who are either primary refractory or have early recurrence following front-line therapy. 

At EHA 2025, Autolus Therapeutics presented the Phase Ib/II FELIX trial investigating Obe-cel for the treatment of R/R B-ALL. The results demonstrated that at a median follow-up of 21.5 months, the Overall Remission Rate (ORR) was 72.2% in patients aged <55 years vs. 87.5% in patients aged ≥55 years. Among responders, 84.2% of patients aged <55 years and 83.3% of patients aged ≥55 years with ≥1 post-infusion next-generation sequencing result achieved measurable residual disease-negative remission to 10-6 leukemic cells by Month 3. Durable remission at 1 year post infusion was observed in 68.3% and 51.8% of patients aged <55 and ≥55 years, respectively. Event-free Survival (EFS) and Overall Survival (OS) were comparable in pts aged <55 and ≥55 years: median EFS was 14.3 vs. 11.7 months, respectively; median OS was 15.5 vs. 16.8 months, respectively. While in remission, 29.8% of patients aged <55 years and 2.4% of patients aged ≥55 years proceeded to consolidative Stem Cell Transplant (SCT). Incidence of Grade ≥3 CRS and ICANS was low for patients aged <55 and ≥55 years, respectively. Treatment-related mortality within 3 months post obe-cel infusion was 0% in patients aged <55 years vs 4.2% in patients aged ≥55 years. CAR T-cell persistence was similar in both age groups.

KOL insights

“Obe-cel’s combination of favorable tolerability and potential long-term outcomes could offer an important new treatment option for patients in the EU.”– Expert Opinion

“With obe-cel, investigators tried to develop a low-affinity CD19 binder that would allow the CAR T cells to bind and then release rapidly; the hope was this would do two things: the first was that it would decrease (some of) the toxicity associated with CAR T-cell therapy, specifically cytokine release syndrome (CRS) and neurologic adverse effects (AEs). The second is that it would improve the health of the T cell and limit T-cell exhaustion so the T cells can stay active for a longer period.”– Expert Opinion

Conclusion

In the last few years, immunotherapy has undergone a new phase of development which is linked to the development of CAR-T cell therapy. It is anticipated that CAR-T cells will bring out the next big leap forward in leukemia immunotherapy. In 2017, the US FDA made a historic decision by approving KYMRIAH (tisangenlecleucel), the first-ever CAR-T cell therapy for the treatment of acute lymphoblastic leukemia. In addition, later in October 2021, the FDA approved another CAR-T cell therapy, TECARTUS (brexucabtagene autoleucel) for adult patients 26 years of age and above with R/R B-cell precursor ALL. In November 2024, FDA approved AUCATZYL (obecabtagene autoleucel) for R/R B-ALL.

obe-cel is a notable recent addition to the ALL treatment paradigm that produces a high incidence of durable responses with lower incidences of immune-related toxicities in patients with relapsed/refractory disease. The construct includes a 4-1BB costimulatory domain, but it's uniquely engineered with a mutagenized receptor antibody that features a rapid off-rate. This means the CAR-T cell disengages from its target within seconds to a minute—much faster than with other CAR-T therapies like brexu-cel or tisa-cel, which have slower off-rates. In theory, this quicker dissociation may reduce T-cell exhaustion and cytokine activation, potentially improving outcomes and enhancing tolerability.