Abstract
Introduction:Inotuzumab ozogamicin (InO) is a CD22-targeted antibody drug conjugate approved for relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). InO has shown promising results as a component of transitioning therapy prior to chimeric antigen receptor T-cell therapy (CAR-T) (Kantarjian et al., 2019). However, real-world data on the use and outcomes of InO prior to or as a bridging therapy to CAR-T remain limited (Laetsch et al. 2023; Shah et al. 2021; Lin et al. 2024). The INO-TRANSIT study aimed to describe the real-world demographics, clinical characteristics and treatment outcomes in R/R B-ALL patients treated with InO prior to CAR-T.
Methods:Data were drawn from an observational chart review of patients with R/R B-ALL receiving InO prior to CAR-T from sites in Spain, the UK and the US from December 2024–June 2025. Patients were ≥18 years at index and received InO to facilitate CD19-directed CAR-T (even if CAR-T was not administered). Electronic case report forms captured patient demographics, clinical characteristics and treatment outcomes. Index was first InO dose (01 June 2017 onwards), with a minimum follow-up of three months post-index. Overall survival (OS) and time to next treatment (TTNT) were evaluated via Kaplan-Meier estimations (with 95% CIs).
Results:Of the 84 patients analyzed, median (IQR) age was 40.0 (24.0, 59.0) years, 78.6% were White and 57.1% were male. Most patients (73.2%) had relapsed disease, 25.5% were refractory. 20.2% of patients had extramedullary disease at their R/R B-ALL diagnosis. Prior to index, 35.7% of patients received a hematopoietic stem cell transplant, 31.0% received blinatumomab and 4.8% received InO. At index, 14.3% of patients were Philadelphia chromosome (Ph) positive, 6.0% were Ph-like and 25.0% of patients had other cytogenetic abnormalities. Median (IQR) bone marrow blast (BMB) count was 62.5% (18.0%, 89.5%). All patients underwent at least 1 cycle of InO prior to CAR-T, 21.4% received 2 cycles and 3.6% received ≥3 cycles. Most patients (73.8%) received InO as a monotherapy. Overall, 45.3% of patients first received InO prior to apheresis and 54.7% between apheresis and CAR-T infusion. Upon InO completion, 46.5% of patients achieved CR, CR with partial hematologic recovery (CRh) or CR with incomplete hematologic recovery (CRi). 26.2% of patients were refractory to InO and 9.5% had progressive disease. Of those assessed (n=65), 41.5% tested negative for minimal residual disease (MRD) after their first and 43.1% after their last cycle of InO. Median (IQR) BMB count after last dose of InO was 2.0% (0.0%, 41.0%), and 66.0% patients had BMB <5%. Median (IQR) TTNT was 35.0 (22.0, 57.0) days, inclusive of CAR-T initiation. Leukapheresis was performed successfully on all patients (n=84); 71 (84.5%) received CAR-T infusion, 9 (10.7%) received another therapy and 4 (4.8%) went into palliative care. CAR-T treatment details were available for 64 patients. Of these, 29.7% received tisagenlecleucel, 34.4% received brexucabtagene autoleucel and 35.9% received another CD19-directed CAR-T product. CAR-T was infused as salvage 1 (34.4%), salvage 2 (29.7%) or salvage 3 or later (26.6%). Overall, 76.7% (n=56/73) of patients achieved CR/CRh/CRi after CAR-T or another therapy. A further 6.8% had refractory disease and 6.8% had progressive disease. CR was maintained for 68.8% of patients until six months after CAR-T. After infusion, 35.9% of patients had B-cell recovery. At 12 months after CAR-T infusion, an estimated 72.5% patients survived and 62.4% had not initiated another salvage therapy. Median OS was not reached. Most patients were alive at the time of data collection (57.3%). Of those who died (42.7%), ALL disease progression was responsible in 82.9% of patients while 11.4% died due to ALL treatment-related causes. Veno-occlusive disease (VOD) was diagnosed in 7.1% of patients at any point during their ALL treatment; a further 4.8% had suspected VOD. 46.4% of patients were diagnosed with neutropenic sepsis at any point during their diagnosis and treatment.
Conclusions:Most patients who received InO prior to CAR-T successfully received treatment, achieving CR after CAR-T. Leukapheresis after InO treatment was feasible, with meaningful 12-month post-CAR-T OS, and the incidence of VOD at any time was low. While larger, comparative studies are required to determine optimal strategies before CAR-T, this study suggests that InO may be used effectively prior to CAR-T.
