Efficacy and safety profile of inaticabtagene autoleucel in Chinese adult patients with B-cell acute lymphoblastic leukemia who relapsed after their transplant: Insights from real-world data

Abstract Introduction Limited therapeutic options are available for adult patients with B-cell acute lymphoblastic leukemia (B-ALL) who relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). With conventional therapies, the prognosis for such relapsed B-ALL cases remain dismal. However, CD19-targeted chimeric antigen receptor T cell (CAR-T) therapy has achieved high complete remission (CR) rates in this setting. Inaticabtagene autoleucel (Inati-cel) is a CD19- CAR T cell featuring a CD19 single-chain variable fragment (scFv) derived from an HI19a clone and a 4-1BB/CD3-ζ costimulatory domain. It has demonstrated a high minimal residual disease (MRD)-negative CR/CR with incomplete count recovery (CRi) rate (85.4%) and an estimated 2-year overall survival (OS) rate of 55.2% (Wang Y. et al., Blood Adv., 2025). We report real-world data on Inati-cel use in patients with B-ALL who relapsed after HSCT, evaluating its potential to improve treatment outcomes. Methods We conducted a multi-institutional real-world study of Inati-cel (NCT06450067), enrolling patients treated from 2024 onwards. Key endpoints included OS, overall response rate (ORR), minimal residual disease (MRD) negativity rate, duration of response (DOR), relapse-free survival (RFS), and CAR-T-related adverse events (AEs). Both OS and RFS were calculated from the day of Inati-cel infusion. Results From January 8, 2024, to July 20, 2025, 156 patients received Inati-cel. Of these cases, 31 in post-HSCT relapses underwent efficacy and safety evaluations. Their median age was 36 years (range: 20–61 years). The patients were pretreated with a median of 2 prior lines of therapy (range: 1–5 lines). Prior therapies included blinatumomab (38.7%) and inotuzumab ozogamicin (22.6%). Eleven (35.5%) had extramedullary relapses, including 7 with central nervous system leukemia. High-risk genetic alterations carried by the patients included Ph positivity (13, 41.9%), TP53 deletion or mutation (3, 9.7%), mixed-lineage leukemia rearrangement (3, 9.7%), and alterations in IKZF1 (5, 16.1%). The median infusion dose was 0.60 (range: 0.42–1.00) × 108 viable CAR-T cells. All but one patient received bridging therapy. The median interval from apheresis to reinfusion was 37 days (range: 20–98 days). With a median follow-up of 7.33 months (range: 0.85–16.93 months), the best ORR across all caese was 83.9%; among responders, the MRD negativity rate (assessed using flow cytometry) was 96.2%. Notably, of the 11 with extramedullary disease, the ORR was 72.7%. Post-infusion, Inati-cel expansion was observed even in caese with MRD-negative CR pre-infusion, peaking around day 14. The longest duration of detectability was 12 months post-infusion in a caes in sustained CR. Notably, detectable CAR-T cells were observed in some patients' cerebrospinal fluid. While the median OS and RFS have not yet been reached, the estimated 1-year OS, RFS, and DOR rates were 64.5%, 69.8%, and 83.2%, respectively. Patients with and without prior blinatumomab exposure had similar OS (p = 0.62) and RFS (p = 0.58); the same was true for prior inotuzumab ozogamicin exposure (p = 0.86 and p = 0.67, respectively). Among patients who received sequential maintenance therapy versus those who did not, the 12-month OS and RFS were 91.2% vs. 51.3% (p = 0.185) and 91.6% vs. 55.4% (p = 0.031), respectively. No cases underwent subsequent allo-HSCT while in remission. Subsequent maintenance therapies included tyrosine kinase inhibitors (TKIs; n = 6), low-dose chemotherapy (n = 5), and inotuzumab ozogamicin (n = 3). Two relapses were observed, both with CD19-positive patients. Five patients died: 3 from disease progression, 1 from infection, and 1 from unknown causes (more than 3 months after Inati-cel infusion). The most common AEs of special interest were cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The incidence rates of CRS and ICANS were 45.2% and 3.2%, respectively, while grade ≥ 3 CRS and ICANS occurred in 3.2% and 0.0%, respectively. In the 11 extramedullary patients, no ICANS and no ≥ grade 3 CRS occurred. All patients recovered without sequelae. ConclusionReal-world data demonstrate that Inati-cel exhibits excellent efficacy in patients with B-ALL who relapse after HSCT and in patients with active extramedullary disease; its safety was also established. Extended follow-up is warranted to fully characterize the long-term outcomes of Inati-cel use.