For adult patients with B-cell acute lymphoblastic leukemia (B-ALL) who relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT), treatment options remain very limited, and outcomes with conventional therapies are generally poor. In recent years, CD19-targeted chimeric antigen receptor T-cell (CAR-T) therapy has shown encouraging complete remission (CR) rates in this setting.
Inaticabtagene Autoleucel is a CD19-directed CAR-T cell therapy, with its single-chain variable fragment (scFv) derived from the HI19a clone and incorporating a 4-1BB/CD3-ζ co-stimulatory domain. Previous studies have reported a high MRD-negative complete remission/CR with incomplete hematologic recovery (CRi) rate of 85.4%, along with an estimated 2-year overall survival (OS) rate of 55.2%. In this study, real-world data were collected to further evaluate its efficacy and safety in patients with B-ALL who relapsed after HSCT.
Results
Between January 8, 2024, and July 20, 2025, a total of 156 patients received Inaticabtagene Autoleucel, among whom 31 patients with post-HSCT relapse were included in the efficacy and safety analysis. The median age of these patients was 36 years (range, 20–61), and they had received a median of 2 prior lines of therapy (range, 1–5). Prior treatments included blinatumomab in 38.7% of patients and inotuzumab ozogamicin in 22.6%. Notably, 35.5% of patients had extramedullary relapse, including 7 cases with central nervous system (CNS) involvement. High-risk genetic features were also observed, including Philadelphia chromosome positivity (41.9%), TP53 mutation or deletion (9.7%), MLL rearrangement (9.7%), and IKZF1 alterations (16.1%).
The median infused dose of CAR-T cells was 0.60 × 10⁸ cells (range, 0.42–1.00 × 10⁸). Almost all patients received bridging therapy prior to infusion. The median time from leukapheresis to infusion was 37 days (range, 20–98 days). With a median follow-up of 7.33 months (range, 0.85–16.93 months), the best overall response rate (ORR) reached 83.9%. Among responders, the MRD-negative rate assessed by flow cytometry was as high as 96.2%. In patients with extramedullary disease, the ORR was 72.7%.
Following infusion, CAR-T cell expansion was observed even in MRD-negative CR patients, with peak expansion occurring around Day 14. In patients with sustained complete remission, CAR-T cells remained detectable for up to 12 months. Notably, CAR-T cells were also detected in the cerebrospinal fluid of some patients. Although the median OS and relapse-free survival (RFS) had not yet been reached, the estimated 1-year OS, RFS, and duration of response (DOR) rates were 64.5%, 69.8%, and 83.2%, respectively.
Further analysis showed that prior exposure to blinatumomab or inotuzumab ozogamicin did not significantly impact OS or RFS outcomes. However, patients who received sequential maintenance therapy after CAR-T infusion demonstrated improved survival outcomes compared to those who did not, with 12-month OS rates of 91.2% versus 51.3% and RFS rates of 91.6% versus 55.4%. Maintenance strategies included tyrosine kinase inhibitors (TKIs), low-dose chemotherapy, and inotuzumab ozogamicin. Importantly, no patients underwent subsequent allo-HSCT after achieving remission.
During follow-up, 2 patients experienced relapse, both of whom remained CD19-positive. A total of 5 deaths were reported, including 3 due to disease progression, 1 due to infection, and 1 from an unknown cause occurring more than 3 months after infusion.
In terms of safety, the most commonly observed adverse events were cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The incidence of CRS and ICANS was 45.2% and 3.2%, respectively, while severe (grade ≥3) CRS and ICANS were reported in 3.2% and 0% of patients. Among patients with extramedullary disease, no cases of ICANS or severe CRS were observed. All patients recovered without long-term sequelae.
Conclusion
Inaticabtagene Autoleucel demonstrates high response rates, deep MRD-negative remissions, durable clinical benefits, and a favorable safety profile in adult B-ALL patients who relapse after allo-HSCT. These real-world findings highlight its strong potential as an effective treatment option for this highly challenging patient population.
