Introduction: Autologous hematopoietic stem cell transplantation (auto-HSCT) is an effective treatment option for patients with adult B-cell acute lymphoblastic leukemia (B-ALL) who achieve minimal residual disease (MRD)-negative status after first-line therapy. However, high-risk patients with B-ALL still face relapse risks. Therefore, enhancing post-transplant leukemia clearance is critical. Inaticabtagene autoleucel (Inati-cel), a CD19-targeted CAR-T cell product comprising a single-chain variable fragment derived from the HI19a clone and a 4-1BB/CD3-ζ costimulatory domain, has demonstrated potent antileukemic activity in relapsed/refractory (r/r) B-ALL. Combining auto-HSCT with autologous CD19-CAR-T cell infusion may eliminate residual leukemia cells and reduce relapse risk. We present an interim analysis of a phase II study evaluating the efficacy and safety of auto-HSCT combined with Inati-cel in adults with high-risk B-ALL.

Methods: This single-arm phase II study (NCT06608342) enrolled adult B-ALL patients with high-risk features who achieved complete remission (CR) and MRD negativity after induction and consolidation therapy, starting in April 2024. All patients received myeloablative conditioning treatment followed by infusion of cryopreserved autologous stem cells. A single infusion of Inati-cel was administered on day 7 post-transplant. Follow-up visits were scheduled at 1, 2, 3, 4, 5, 6, 9, 12, 18, and 24 months posttransplant. Key assessments included CAR-T expansion kinetics (flow cytometry), serum cytokine levels, hematopoietic reconstitution, and MRD status (qPCR, sensitivity: 10-6). The primary endpoint is two-year relapse incidence. Secondary endpoints include non-relapse mortality, progression-free survival (PFS), overall survival (OS), infection incidence, and the Karnofsky Performance Status score.

Results: By July 20, 2025, twelve patients' results were included in the interim analysis. The median age was 36 years (range: 19–52 years), and 66.7% were male. High-risk genetic abnormalities were detected in 66.7% of the patients, including BCR-ABL1 (33.3%), MLL rearrangement (16.7%), IKZF1 mutation (8.3%), and MEF2D rearrangement (8.3%). All patients achieved CR with MRD negativity prior to auto-HSCT and received a median of 2 (range: 1–3) consolidation cycles. Of the 12 patients, 10 underwent conditioning regimens incorporating total body irradiation (TBI), while the remaining 2 received non-TBI-based conditioning prior to stem cell infusion. The median CD34⁺ dose was 2.86 (range: 2.01–3.40) × 10⁶/kg, and the median Inati-cel dose was 0.59 (range: 0.49–0.68) × 10⁸ cells.

At a median follow-up of 7.35 months (range: 0.8–13.7 months), all patients remained MRD-negative. Neither median PFS nor OS have been reached, while the one-year PFS and OS rates were both 100%. The median time to neutrophil and platelet engraftment was 12.5 days (range: 9–17 days) and 18.5 days (range: 10–159 days) posttransplant, respectively. Inati-cel infusion had no impact on hematopoietic recovery.

CAR-T cells expanded in vivo with peak levels around day 14 and remained detectable for up to 12 months in one patient. In most patients, IL-6 and IL-10 levels peaked within 7 days after CAR-T cell infusion and subsequently declined. Additionally, an increase in TNF-α was observed in 2 patients, IL-12p70 in 4 patients, IL-8 in 5 patients, and IL-5 in 6 patients. Following CAR-T infusion, one patient developed grade 2 cytokine release syndrome (CRS); no cases of immune effector cell-associated neurotoxicity syndrome (ICANS) were observed. Two patients developed bacteremia caused by Klebsiella pneumoniae and Escherichia coli. Nine patients experienced intestinal infections, one had a pulmonary infection, and three developed perianal infections. All infections occurred during the neutropenic phase and were successfully managed, with no infection-related fatalities.

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2025
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