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ACUTE LYMPHOBLASTIC LEUKEMIA

CD22 CAR T cells demonstrate high response rates and safety in pediatric and adult B-ALL: Phase 1b results

Leukemia (2024)Cite this article

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Abstract

Chimeric antigen receptor (CAR) T cells targeting CD22 (CD22-CAR) provide a therapeutic option for patients with CD22+ malignancies with progression after CD19-directed therapies. Using on-site, automated, closed-loop manufacturing, we conducted parallel Phase 1b clinical trials investigating a humanized CD22-CAR with 41BB costimulatory domain in children and adults with heavily treated, relapsed/refractory (r/r) B-ALL. Of 19 patients enrolled, 18 had successful CD22-CAR manufacturing, and 16 patients were infused. High grade (3–4) cytokine release syndrome (CRS) and immune effector-cell-associated neurotoxicity syndrome (ICANS) each occurred in only one patient; however, three patients experienced immune-effector-cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS). Twelve of 16 patients (75%) achieved CR with an overall 56% MRD-negative CR rate. Duration of response was overall limited (median 77 days), and CD22 expression was downregulated in 4/12 (33%) available samples at relapse. In summary, we demonstrate that closed-loop manufacturing of CD22-CAR T cells is feasible and is associated with a favorable safety profile and high CR rates in pediatric and adult r/r B-ALL, a cohort with limited CD22-CAR reporting.

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Fig. 1: Consort diagram of patients with r/r B-ALL enrolled on pediatric or adult CD22-CAR T cell trials.
Fig. 2: Swimmer plot, progression-free survival, and overall survival.
Fig. 3: CAR T-cell expansion by flow cytometry.

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Data availability

For original deidentified patient data or the clinical trial protocol please contact LM (lmuffly@stanford.edu).

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Acknowledgements

The authors would like to acknowledge Ted Gooley, Ph.D. of the Fred Hutchinson Cancer Research Center for his assistance with statistical analysis as well as Nirali Shah M.D., M.H.Sc. and the National Cancer Institute for providing additional viral vector to allow more patients to enroll on the CD22-CAR studies at Stanford.

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Author notes

  1. These authors contributed equally: Liora M. Schultz, Nikeshan Jeyakumar.

Authors and Affiliations

  1. Division of Pediatric Hematology/Oncology, Stanford University, Stanford, CA, USA

    Liora M. Schultz, Courtney Erickson, Ashley Jacobs, Jennifer Moon, Christina Baggott, Crystal L. Mackall, Kara L. Davis & Sneha Ramakrishna

  2. Center for Cancer Cell Therapy, Stanford University, Stanford, CA, USA

    Liora M. Schultz, Anne Marijn Kramer, Bita Sahaf, Emily Egeler, Sharon Mavroukakis, Steven A. Feldman, David B. Miklos, Crystal L. Mackall, Kara L. Davis, Matthew Frank, Sneha Ramakrishna & Lori Muffly

  3. Division of Hematology, Stanford University, Stanford, CA, USA

    Nikeshan Jeyakumar, Hrishi Srinagesh, Mark Hamilton & Michaela Liedtke

  4. Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University, Stanford, CA, USA

    Parveen Shiraz, Neha Agarwal, Sally Arai, Sushma Bharadwaj, Laura J. Johnston, Robert Lowsky, Everett Meyer, Robert Negrin, Andrew Rezvani, Judy Shizuru, Surbhi Sidana, David B. Miklos, Matthew Frank & Lori Muffly

  5. Laboratory for Cell and Gene Medicine, Stanford University, Stanford, CA, USA

    Ramya Tunuguntla, Nikolaos Gkitsas-Long, Aidan Retherford, Annie Kathleen Brown, Anne-Louise Gramstrap-Petersen, Raquel Martin Ibañez & Steven A. Feldman

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Contributions

All authors were responsible for data collection and analysis, revision of the manuscript, and final approval. NJ, LS, LM, and SR were primarily responsible for manuscript writing.

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Correspondence to Lori Muffly.

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Schultz, L.M., Jeyakumar, N., Kramer, A.M. et al. CD22 CAR T cells demonstrate high response rates and safety in pediatric and adult B-ALL: Phase 1b results. Leukemia (2024). https://doi.org/10.1038/s41375-024-02220-y

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