Efficacy and safety profile of inaticabtagene autoleucel in Chinese patients with Philadelphia chromosome-positive b-ALL: Insights from real-world data

Abstract

Abstract Introduction Inaticabtagene autoleucel (Inati-cel) featuring a CD19 single-chain variable fragment derived from an HI19a clone and a 4-1BB/CD3-ζ costimulatory domain has been approved in China for adult patients with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). Inati-cel yielded a high minimal residual disease (MRD)-negative complete remission (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). Adding tyrosine kinase inhibitors (TKIs) significantly improves the prognosis of Ph-positive (Ph+) B-ALL. However, some patients remain resistant to conventional therapies or relapse post-treatment. Emerging evidence indicates that chemotherapy-free treatments for Ph+ B-ALL are associated with high rates of molecular response and favorable survival outcomes. Herein, we evaluate the efficacy and safety of Inati-cel in Ph+ B-ALL patients. Methods We conducted a multi-institutional real-world study of Inati-cel (NCT06450067), enrolling patients treated since 2024. Endpoints included OS, complete hematologic response, complete molecular response, relapse-free survival (RFS), and other relevant measures. 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, among whom 54 cases with Ph+ B-ALL underwent efficacy and safety evaluations. Their median age was 45 years (range: 15–76 years), with 13 patients (24.1%) aged ≥ 60 years. The patients had received a median of 1 prior line of therapy (range: 1–5). Prior therapies included hematopoietic stem cell transplantation (HSCT) (24.1%), inotuzumab ozogamicin (14.8%), and blinatumomab (24.1%). Patients with R/R disease and those in first complete remission (CR1) each accounted for 50%. Fourteen patients had extramedullary relapses, including 13 with central nervous system leukemia (CNSL). The median infusion dose was 0.60 (range: 0.44–1.00) × 108viable CAR-T cells, with 88.9% of patients receiving bridge therapy. The median interval from apheresis to infusion was 38 days (range: 23–181). With a median follow-up of 6.25 months (range: 0.95–16.93), the best overall response rate (ORR) in the R/R patients was 96.7%; among responders, the MRD negativity rate (assessed using flow cytometry) was 100.0%. All 5 patients with baseline MRD positivity achieved MRD negativity after Inati-cel administration. Of the 48 patients with available BCR/ABL1 fusion genes assessed using q-PCR post-infusion, 87.5% achieved negativity. Notably, of the 13 patients with CNSL, the ORR was 92.3%. Post-infusion, Inati-cel expanded even in patients with MRD-negative CR pre-infusion, with peak levels observed around day 14. The longest duration of detectability was 15 months post-infusion in a patient in sustained CR. Detectable CAR-T cells were observed in the cerebrospinal fluid of some patients. No patients underwent subsequent allo-HSCT while in remission; most received maintenance therapy with TKIs, with the longest RFS exceeding 16 months. The median OS and RFS were not reached in the overall population. In the R/R and CR1 patients, the estimated 1-year OS and RFS rates were 93.3% and 84.7%, respectively, and 100% and 95.2%, respectively. In a univariate analysis, IKZF1 abnormalities, prior exposure to inotuzumab ozogamicin, and the fusion gene turning negative after Inati-cel use were not significant prognostic factors for RFS or OS. Three relapses were documented: 1 with CD19 positivity, and 2 with CD19 negativity. Five patients exhibited persistent BCR/ABL1 fusion gene positivity, and 3 experienced fusion gene relapses. One patient died from unknown causes (more than 3 months after Inati-cel infusion). The most common adverse events of interest were cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). CRS occurred in 50.0% of patients, with only 1 case of grade 3; ICANS developed in 2 patients-both grade 1. All patients recovered without sequelae: 9 received corticosteroids, and 11 received tocilizumab. Conclusion Real-world data demonstrate that Inati-cel exhibits excellent efficacy in patients with Ph+ B-ALL, yielding low toxicity, short treatment cycles, high complete molecular response rates, and favorable long-term survival. Extended follow-up could illuminate the long-term outcomes of Inati-cel use.