Real-world data presented at ASH 2025 confirm the high efficacy, favorable safety, and consistent in vivo expansion of inaticabtagene autoleucel, including in patients with active CNS involvement.
Background
Inaticabtagene autoleucel (Yorwida) is a CD19-directed CAR-T cell therapy incorporating a single-chain variable fragment (scFv) derived from the HI19a clone, together with a 4-1BB/CD3-ζ costimulatory domain. It has been approved in China for the treatment of adult patients with relapsed or refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL). The pivotal registration study demonstrated a high MRD-negative complete remission (CR/CRi) rate of 85.4% and an estimated 2-year overall survival (OS) rate of 55.2%.
This real-world study reports outcomes from a larger patient cohort and presents key subgroup analyses.
Results
Between November 20, 2023, and July 22, 2025, a total of 210 patients underwent leukapheresis. Among them, 156 patients received infusion of inaticabtagene autoleucel, and 145 patients were included in the efficacy and safety analyses. Fifty-four patients did not proceed to infusion due to manufacturing failure (4 cases: 1 due to insufficient lymphocytes in the apheresis product, 1 due to an unfavorable CD4/CD8 ratio, and 2 due to unknown reasons), infection (2 cases), or were still awaiting infusion.
The median age was 39 years (range: 13–76), including 28 patients aged ≥60 years. The median number of prior treatment lines was 1 (range: 1–5). Prior immunotherapies included allogeneic hematopoietic stem cell transplantation (allo-HSCT, 21.4%), inotuzumab ozogamicin (18.6%), and blinatumomab (28.3%).
Eighty-one patients (55.9%) had relapsed or refractory ALL, including 15 patients (10.3%) with primary refractory disease and 26 patients (17.9%) with extramedullary involvement. Sixty-four patients (44.1%) were treated in first complete remission (CR1), including 12 with MRD-positive disease and 52 with MRD-negative disease.
Approximately half of the patients harbored high-risk genetic abnormalities, including TP53 deletion or mutation (7.6%), MLL rearrangement (9.7%), IKZF1 alterations (16.6%), Ph-like ALL (4.8%), and PAX5 alterations (5.5%).
The median infused dose was 0.60 × 10⁸ viable CAR-T cells (range: 0.42–1.14 × 10⁸). Bridging therapy was administered to 88% of patients. With a median follow-up of 6.18 months (range: 0.85–19.13 months), the best overall response rate (BOR) in the overall population was 92.4% (134/145), with an MRD-negative rate of 97.8%.
Among r/r ALL patients, the BOR was 86.4% (70/81), and the MRD-negative rate was 97.1%. All 12 patients with MRD-positive disease achieved MRD negativity after treatment. In patients with extramedullary disease, the overall response rate was 80%. Notably, 15 of 16 patients with central nervous system leukemia (CNSL) achieved complete remission.
Among 71 patients evaluated for MRD using IG gene rearrangement by qPCR or NGS, 87.3% achieved MRD negativity. Post-infusion expansion of inaticabtagene autoleucel was observed in vivo, including in patients who were already in MRD-negative CR prior to infusion, with peak expansion occurring around day 14. CAR-T cells remained detectable for up to 15 months post-infusion, during which patients maintained continuous remission.
At data cutoff, median OS, relapse-free survival (RFS), and duration of response (DOR) had not been reached. Estimated 1-year OS, RFS, and DOR were 89.3%, 78.1%, and 84.7%, respectively.
Seven patients underwent allo-HSCT following inaticabtagene autoleucel therapy. Among all responders, no significant differences in OS or RFS were observed between patients who did or did not receive sequential transplantation (P = 0.59 and 0.60, respectively). However, patients who received subsequent anti-tumor therapy demonstrated significantly improved RFS compared with those who did not (P = 0.003).
Thirteen patients experienced relapse, including six with CD19-positive relapse, six with CD19-negative relapse, and one with unknown status. Univariate analysis showed that prior lines of therapy, age, prior exposure to blinatumomab or inotuzumab ozogamicin, and transplant history were not significant prognostic factors for OS or RFS.
A total of nine deaths occurred: five due to disease progression, two due to transplant-related complications, one due to infection, and one of unknown cause.
The primary adverse events of interest were cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS), with incidences of 53.8% and 4.9%, respectively. Grade ≥3 CRS and ICANS both occurred in 2.8% of patients. All patients fully recovered without long-term sequelae. Corticosteroids were used in 38 patients, and tocilizumab or siltuximab was administered in 33 patients.
