Deeper remission achievement and longer leukemia-free survival with inati-cel as consolidation therapy in allogeneic transplant-ineligible adolescent and adult patients with B-ALL

Abstract

Abstract Introduction: CD19 chimeric antigen receptor T-cell (CAR-T) therapy yields high remission rates in adult B-cell acute lymphoblastic leukemia (B-ALL). However, its impact on long-term leukemia-free survival remains limited, with the primary reason being that the efficacy of CAR-T cells is closely linked to tumor burden. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) stands as the most common consolidation strategy for adult B-ALL in remission. However, some patients are ineligible due to donor availabilty and comorbidities, while others decline based on personal risk assessments. Inaticabtagene autoleucel (Inati-cel), a novel CD19 CAR T-cell therapy with a distinct single-chain variable fragment, demonstrated significant clinical efficacy. Accordingly, our study seeks to investigate whether inati-cel can serve as a consolidation therapy during the remission phase of B-ALL, potentially acting as an alternative to allo-HSCT.Methods:Adolescents and adults (Ages: 14~80 years) with B-cell acute lymphoblastic leukemia in CR/CRi (bone marrow blasts <5%, no extramedullary disease) who were not ineligible for allo-HSCT in the Department of Hematology, the Zhujiang Hospital, Southern Medical University, were enrolled. Patients underwent leukapheresis to obtain T cells for inati-cel manufacturing. All patients received lymphodepletion with fludarabine (30 mg/m2/d ×3 days) and cyclophosphamide (500 mg/m2/d ×2 days) followed by Ina-cel infusion (0.6×108 live CAR-T cells). Bone marrow assessments were performed at 1 month, 3 months, and 1 year after CAR-T cell infusion. CAR-T cell expansion kinetics was assessed by flow cytometry. Subsequent follow-up was performed. The primary endpoint was 1-year leukemia-free survival (LFS) rate. Other endpoints included cumulative incidence of relapse (CIR), overall survival rate (OS) rate and MRD-negative remission rate, the incidence of adverse events (AEs) such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS) and infections, as well as the peak value of CAR-T cell expansion kinetics. All patients provided informed consent and agreed to follow the study protocol. The study has been registered on clinicaltrial.gov (NCT07072494).Results: From January 2024 to April 2025, a total of 11 patients with B-ALL in CR/CRi, ineligible for allo-HSCT, who had received Inati-cel infusion, were analyzed. Among the 11 patients, there were 6 males and 5 females, with a median age of 32 years (range, 15–67). 5 of them were in the first complete remission (CR1), 6 were in CR2. The last follow-up date was July 15, 2025, with a median follow-up time of 269 days. All patients remained alive, with one patient experiencing relapse on day 82 post CAR-T cell infusion. 1-year LFS rate was 90% (95%CI 47.1, 98.5) and the median LFS was not reached at present. 1-year CIR rate was 10% (95%CI 0.0, 72.321). 1-year OS rate was 100% (95%CI NR) and the median OS was not reached. Of the 11 patients who received CAR-T infusion during CR, 7 had negative minimal residual disease (MRD) prior to infusion (63.6%), while 4 had positive MRD. All 4 MRD-positive patients converted to negative after infusion, resulting in an MRD negativity rate of 100%. CAR-T expansion kinetics analysis revealed a median time to peak (Tmax) of 15 days (range, 10-60) by flow cytometry. The median absolute value of CAR-T cells was 85.78 cells/μL(range, 0.9786 to 1011.74). Currently, all patients are under follow-up, with CAR-T cells detected in their peripheral blood. In safety, CRS occurred in 9 patients (six with grade 1, two with grade 2 and only one with grade 3); and ICANS occurred in 2 patients (one with grade 2 and one with grade 3) . Specially, only one patient had grade 3 CRS and grade 3 ICANS, characterized by high fever and hypotension, and was managed with tocilizumab in combination with dexamethasone (80 mg). Additionally, 7 patients (63.6%) suffered from cytopenia. 3 (27.27%) patients had infection, which resolved after treatment.Conclusions: Our preliminary results of the intervention study demonstrate inati-cel, a CD19 CAR-T cell therapy leads to high MRD-negativity conversion and survival rates with manageable toxicity in transplant-ineligible B-ALL patients. More patients are being enrolled and followed up. Long-term survival data are likely to support CD19 CAR-T cell therapy as a new paradigm for consolidation therapy for B-ALL patients.