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

Liora M. Schultz; Nikeshan Jeyakumar; Anne Marijn Kramer; Bita Sahaf; Hrishi Srinagesh; Parveen Shiraz; Neha Agarwal; Mark Hamilton; Courtney Erickson; Ashley Jacobs; Jennifer Moon; Christina Baggott; Sally Arai; Sushma Bharadwaj; Laura J. Johnston; Michaela Liedtke; Robert Lowsky; Everett Meyer; Robert Negrin; Andrew Rezvani; Judy Shizuru; Surbhi Sidana; Emily Egeler; Sharon Mavroukakis; Ramya Tunuguntla; Nikolaos Gkitsas-Long; Aidan Retherford; Annie Kathleen Brown; Anne Louise Gramstrap-Petersen; Raquel Martin Ibañez; Steven A. Feldman; David B. Miklos; Crystal L. Mackall; Kara L. Davis; Matthew Frank; Sneha Ramakrishna; Lori Muffly

doi:10.1038/s41375-024-02220-y

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

Liora M. Schultz, Nikeshan Jeyakumar, Anne Marijn Kramer, Bita Sahaf, Hrishi Srinagesh, Parveen Shiraz, Neha Agarwal, Mark Hamilton, Courtney Erickson, Ashley Jacobs, Jennifer Moon, Christina Baggott, Sally Arai, Sushma Bharadwaj, Laura J. Johnston, Michaela Liedtke, Robert Lowsky, Everett Meyer, Robert Negrin, Andrew RezvaniJudy Shizuru, Surbhi Sidana, Emily Egeler, Sharon Mavroukakis, Ramya Tunuguntla, Nikolaos Gkitsas-Long, Aidan Retherford, Annie Kathleen Brown, Anne Louise Gramstrap-Petersen, Raquel Martin Ibañez, Steven A. Feldman, David B. Miklos, Crystal L. Mackall, Kara L. Davis, Matthew Frank, Sneha Ramakrishna, Lori Muffly

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

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.

Original language	English
Pages (from-to)	963-968
Number of pages	6
Journal	Leukemia
Volume	38
Issue number	5
DOIs	https://doi.org/10.1038/s41375-024-02220-y
State	Published - May 2024
Externally published	Yes

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Schultz, L. M., Jeyakumar, N., Kramer, A. M., Sahaf, B., Srinagesh, H., Shiraz, P., Agarwal, N., Hamilton, M., Erickson, C., Jacobs, A., Moon, J., Baggott, C., Arai, S., Bharadwaj, S., Johnston, L. J., Liedtke, M., Lowsky, R., Meyer, E., Negrin, R., ... Muffly, L. (2024). CD22 CAR T cells demonstrate high response rates and safety in pediatric and adult B-ALL: Phase 1b results. Leukemia, 38(5), 963-968. https://doi.org/10.1038/s41375-024-02220-y

@article{821c3795da5d4a40b8fcc01afec4e2f0,

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

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.",

author = "Schultz, {Liora M.} and Nikeshan Jeyakumar and Kramer, {Anne Marijn} and Bita Sahaf and Hrishi Srinagesh and Parveen Shiraz and Neha Agarwal and Mark Hamilton and Courtney Erickson and Ashley Jacobs and Jennifer Moon and Christina Baggott and Sally Arai and Sushma Bharadwaj and Johnston, {Laura J.} and Michaela Liedtke and Robert Lowsky and Everett Meyer and Robert Negrin and Andrew Rezvani and Judy Shizuru and Surbhi Sidana and Emily Egeler and Sharon Mavroukakis and Ramya Tunuguntla and Nikolaos Gkitsas-Long and Aidan Retherford and Brown, {Annie Kathleen} and Gramstrap-Petersen, {Anne Louise} and Iba{\~n}ez, {Raquel Martin} and Feldman, {Steven A.} and Miklos, {David B.} and Mackall, {Crystal L.} and Davis, {Kara L.} and Matthew Frank and Sneha Ramakrishna and Lori Muffly",

note = "Publisher Copyright: {\textcopyright} The Author(s), under exclusive licence to Springer Nature Limited 2024.",

year = "2024",

month = may,

doi = "10.1038/s41375-024-02220-y",

language = "English",

volume = "38",

pages = "963--968",

journal = "Leukemia",

issn = "0887-6924",

publisher = "Nature Publishing Group",

number = "5",

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Schultz, LM, Jeyakumar, N, Kramer, AM, Sahaf, B, Srinagesh, H, Shiraz, P, Agarwal, N, Hamilton, M, Erickson, C, Jacobs, A, Moon, J, Baggott, C, Arai, S, Bharadwaj, S, Johnston, LJ, Liedtke, M, Lowsky, R, Meyer, E, Negrin, R, Rezvani, A, Shizuru, J, Sidana, S, Egeler, E, Mavroukakis, S, Tunuguntla, R, Gkitsas-Long, N, Retherford, A, Brown, AK, Gramstrap-Petersen, AL, Ibañez, RM, Feldman, SA, Miklos, DB, Mackall, CL, Davis, KL, Frank, M, Ramakrishna, S & Muffly, L 2024, 'CD22 CAR T cells demonstrate high response rates and safety in pediatric and adult B-ALL: Phase 1b results', Leukemia, vol. 38, no. 5, pp. 963-968. https://doi.org/10.1038/s41375-024-02220-y

TY - JOUR

T1 - CD22 CAR T cells demonstrate high response rates and safety in pediatric and adult B-ALL

T2 - Phase 1b results

AU - Schultz, Liora M.

AU - Jeyakumar, Nikeshan

AU - Kramer, Anne Marijn

AU - Sahaf, Bita

AU - Srinagesh, Hrishi

AU - Shiraz, Parveen

AU - Agarwal, Neha

AU - Hamilton, Mark

AU - Erickson, Courtney

AU - Jacobs, Ashley

AU - Moon, Jennifer

AU - Baggott, Christina

AU - Arai, Sally

AU - Bharadwaj, Sushma

AU - Johnston, Laura J.

AU - Liedtke, Michaela

AU - Lowsky, Robert

AU - Meyer, Everett

AU - Negrin, Robert

AU - Rezvani, Andrew

AU - Shizuru, Judy

AU - Sidana, Surbhi

AU - Egeler, Emily

AU - Mavroukakis, Sharon

AU - Tunuguntla, Ramya

AU - Gkitsas-Long, Nikolaos

AU - Retherford, Aidan

AU - Brown, Annie Kathleen

AU - Gramstrap-Petersen, Anne Louise

AU - Ibañez, Raquel Martin

AU - Feldman, Steven A.

AU - Miklos, David B.

AU - Mackall, Crystal L.

AU - Davis, Kara L.

AU - Frank, Matthew

AU - Ramakrishna, Sneha

AU - Muffly, Lori

PY - 2024/5

Y1 - 2024/5

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85187918986&partnerID=8YFLogxK

U2 - 10.1038/s41375-024-02220-y

DO - 10.1038/s41375-024-02220-y

M3 - Article

C2 - 38491306

AN - SCOPUS:85187918986

SN - 0887-6924

VL - 38

SP - 963

EP - 968

JO - Leukemia

JF - Leukemia

IS - 5

ER -

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

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