Abstract
Introduction: Inaticabtagene autoleucel (Inati-cel), featuring a CD19 scFv derived from the HI19a clone and a 4-1BB/CD3-ζ costimulatory domain, was approved in China for adult patients with r/r B-ALL and demonstrated high MRD-negative CR/CRi rate (85.4%) and an estimated 2-year OS rate of 55.2% (Wang Y et al. Blood Adv. 2025). Here, we report the real-world outcomes with more patients and key subgroups described.
Methods: The multi-center real-world study (NCT06450067) was conducted from 2023. The endpoints included overall remission rate (ORR), minimal residual disease (MRD) negativity rate, overall survival (OS), relapse-free survival (RFS) and other relevant measures. Both OS and RFS were calculated from the day of Inati-cel infusion.
Results: From November 20, 2023, to July 22, 2025, 210 patients underwent leukapheresis, with 156 receiving Inati-cel and 145 included in efficacy and safety analyses. Fifty-four patients underwent apheresis but did not receive the infusion due to manufacture failure (4 pts: 1 for insufficient lymphocytes in the apheresis product, 1 for low CD4/CD8 ratio, and 2 for unknown reasons) or infection (2 pts), or still waiting for infusion. The median age was 39 years (range, 13-76), with 28 patients aged≥60 years. Patients were pretreated with a median of 1 prior lines of therapy (range 1-5). Prior immunotherapies included: HSCT (21.4%), inotuzumab ozogamicin (18.6%), and blinatumomab (28.3%). There were 81 (55.9%) R/R ALL patients:15 (10.3%) primary refractory and 26 (17.9%) with extramedullary lesions, and 64 (44.1%) in CR1 (12 MRD-positive and 52 MRD-negative). About 50% carried high-risk genetic abnormity such as TP53 deletion or mutation (7.6%), MLL rearrangement (9.7%), alterations of IKZF1 (16.6%), Ph-like (4.8%), alterations of PAX5 (5.5%). The median infusion dose was 0.60 (range: 0.42-1.14) ×108CAR-T live cells, with 88% of patients receiving bridge therapy.
With a median follow-up of 6.18 months (range: 0.85–19.13months), the BOR in all patients was 92.4% (134/145), and among the cases with remission, the MRD negativity rate was 97.8%. In R/R ALL caess, the BOR and MRD negativity rate were 86.4% (70/81) and 97.1%, respectively. Among the 12 patients with MRD-positive, the MRD-negativity rate reached 100%. Of the 26 patients with extramedullary disease, the ORR was 80%; notably of the 16 patients with CNSL, 15 attained CR. Of the 71 patients with available MRD results assessed by q-PCR or NGS for IG rearrangement after Inati-cel, 87.3% achieved MRD negative. Following infusion, expansion of Inati-cel was observed, even in patients with MRD-negative CR prior to infusion, with peaking around day 14. The longest detectability lasted up to 15 months post-infusion in a patient maintaining CR.
The median OS, RFS and DOR have not been reached. The estimated 1-year OS, RFS and DOR rates were 89.3%, 78.1% and 84.7%, respectively. Seven proceeded to allo-HSCT following Inati-cel. Among all responsed patients no significant differences were observed in OS and RFS (P = 0.59 and 0.60, respectively) regardless of the subsequent transplant status, however, significant difference in RFS was observed between patients with subsequent anti-tumor treatment and those without (P = 0.003). Thirteen relapses were observed, with 6 CD19-positive, 6 CD19-negative, and 1 with unknown CD19 status. In the univariate analysis, the number of prior treatment lines, age, previous exposure to blinatumomab, or inotuzumab ozogamicin, and prior history of HSCT were not identified as significant prognostic factors for RFS and OS.
A total of 9 patients died: 5 died from disease progression, 2 from transplant-related complications, 1 from infection, and 1 from unknown causes. The most common adverse events (AEs) of special interest were cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The incidence rates of CRS and ICAN were 53.8% and 4.9%, respectively, while grade ≥3 CRS and ICANS occurring in 2.8% and 2.8%, respectively. All patients recovered without sequelae, with 38 treated with corticosteroids, and 33 with tocilizumab or siltuximab.
Conclusion: Real-world data on Inati-cel corroborates its robust response rate, favorable toxicity profile, and survival benefits. Inati-cel demonstrates efficacy in patients with active extramedullary diseases, particularly those with CNSL. In vivo expansion was observed across different disease states.
