Efficacy and safety of commercial CD19 CAR-T (inaticabtagene autoleucel) in relapsed/refractory extramedullary B-ALL: A large multicenter real-world study.

Abstract

e23343 Background: Adult patients with relapsed/refractory (R/R) extramedullary B-ALL have a dismal prognosis with conventional therapies. Despite the success of CD19 CAR-T in hematologic relapse, its efficacy in extramedullary disease remains underexplored, as pivotal trials often excluded these high-risk pts. This large, multicenter, real-world study aims to define the outcomes of Inaticabtagene autoleucel (Inati-cel) in this challenging population. Methods: Eligible patients had R/R extramedullary B-ALL, underwent apheresis for Inati-cel following its approval (November 7, 2023), and completed at least 30 days of follow-up. The primary endpoints were overall survival (OS) and relapse-free survival (RFS). Secondary outcomes included the complete remission (CR) rate, minimal residual disease (MRD) negativity rate, and toxicity profiles. CR was defined as ≤5% bone marrow blasts morphologically, no circulating lymphoblasts, and resolution of extramedullary disease. MRD was evaluated via flow cytometry, RQ-PCR, and/or NGS. CRS and ICANS were graded according to ASTCT criteria. Results: As of the data cutoff (December 31, 2025), a total of 50 patients with R/R extramedullary B-ALL from over 20 centers across China received Inati-cel therapy. The median age was 39.5 years (range, 14–79), and 60% were male. Extramedullary disease involved the central nervous system (CNS) in 64%(32/50) of pts, non-CNS disease in 28%(14/50), and both in 8%(4/50). Following infusion, 41 of 48 evaluable pts (85.4%) achieved CR in both bone marrow and EM disease, with 100% of responders achieving bone marrow MRD negativity. Among pts with CNS involvement, the CR rate was 93.3% (28/30), compared with 78.6% (11/14) in those with non-CNS EM disease and 50% (2/4) in pts with both CNS and non-CNS EM disease. After a median follow-up of 7.2 months, the median OS and RFS had not been reached; Notably, the 1-year OS and RFS rates were 86.8% and 61.9%, respectively. Compared to their Ph-positive counterparts, patients with Ph-negative disease had significantly worse OS (100% vs 76.4%; P = 0.026) and RFS (81.2% vs 45.6%; P = 0.039). Similarly, IKZF1 deletion was associated with significantly poorer OS (89.4% vs 66.7%; P = 0.044) and RFS (67.1% vs 33.3%; P = 0.004). Regarding safety, any-grade CRS occurred in 66% of pts (4% Grade 3–4), and ICANS occurred in 14% (4% Grade 3). All toxicities were manageable and reversible, with no treatment-related deaths. Conclusions: This largest real-world study demonstrates that commercial CD19 CAR-T therapy with Inati-cel induces high response rates and durable survival in adult patients with high-risk R/R extramedullary B-ALL, exhibiting a manageable safety profile. These findings establish Inati-cel as an effective standard-of-care option for this population and support its use even in settings typically excluded from clinical trials.