Abstract
Patients progressing after CD19-targeted immunotherapy in r/r B-ALL experience poor outcomes. CD22-targeted therapies, including CD22 CAR-T cells and Inotuzumab Ozogamicin, show promise as alternatives, although data in those patients is limited. This study retrospectively analyzed 43 r/r B-ALL patients who had previously received CD19-targeted therapy at two centers in China. Among these patients, 27.9% received blinatumomab, 58.1% received CD19 CAR-T cells, and 14% received both. After CD19-targeted therapy, 34.9% of patients experienced CD19-negative relapse, while the remaining patients maintained CD19 expression. Subsequent treatments included CD22 CAR-T cells (55.8%) and InO (44.2%). The median age was 39 (24–56) years, with an overall CR/CRi rate of 54% and 35.1% achieving MRD negativity. Among the 22 patients achieving CR/CRi, 13 (59.1%) experienced relapse. The median relapse-free survival (RFS) was 236 days (95% CI: 132–unreached), and the median OS has not been reached. Multivariate analysis showed similar remission rates and survival for CD22 CAR-T and Inotuzumab Ozogamicin therapies. Patients with extramedullary disease had worse remission rates, and those previously resistant to CD19-targeted therapy had shorter RFS. CD22-targeted therapies offer a potential option for patients progressing after CD19-targeted immunotherapy, but high relapse rates highlight the need for better strategies for lasting remission.
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The data sets used and analyzed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (grant numbers 82370223 and 82425002).
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GW, XZ, HH, and YH designed the study. FS analyzed the data and drafted the manuscript. JY, MZ, SF, JF, RH, YL, and AHC provided subject data and performed data analysis. All authors read and approved the final manuscript.
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Song, F., Yang, J., Zhang, M. et al. CD22-targeted immunotherapy for B-cell acute lymphoblastic leukemia progressing following CD19-targeted immunotherapy. npj Precis. Onc. (2026). https://doi.org/10.1038/s41698-026-01413-1
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DOI: https://doi.org/10.1038/s41698-026-01413-1


