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

• Published in: Leukemia 2024-05, Vol.38 (5), p.963-968
• Main Authors: Schultz, Liora M., Jeyakumar, Nikeshan, Kramer, Anne Marijn, Sahaf, Bita, Srinagesh, Hrishi, Shiraz, Parveen, Agarwal, Neha, Hamilton, Mark, Erickson, Courtney, Jacobs, Ashley, Moon, Jennifer, Baggott, Christina, Arai, Sally, Bharadwaj, Sushma, Johnston, Laura J., Liedtke, Michaela, Lowsky, Robert, Meyer, Everett, Negrin, Robert, Rezvani, Andrew, Shizuru, Judy, Sidana, Surbhi, Egeler, Emily, Mavroukakis, Sharon, Tunuguntla, Ramya, Gkitsas-Long, Nikolaos, Retherford, Aidan, Brown, Annie Kathleen, Gramstrap-Petersen, Anne-Louise, Ibañez, Raquel Martin, Feldman, Steven A., Miklos, David B., Mackall, Crystal L., Davis, Kara L., Frank, Matthew, Ramakrishna, Sneha, Muffly, Lori
• Format: Article
• Language: English
• Subjects: 13/31; 13/44; 38/77; 631/67/1059/2325; 692/308/2779/109/1940; Adolescent; Adult; Cancer Research; CD19 antigen; CD22 antigen; Child; Child, Preschool; Chimeric antigen receptors; Clinical trials; Closed loops; Critical Care Medicine; Down-regulation; Female; Hematology; Histiocytosis; Humans; Immunotherapy, Adoptive - adverse effects; Immunotherapy, Adoptive - methods; Intensive; Internal Medicine; Lymphocytes; Lymphocytes T; Lymphocytosis; Male; Malignancy; Manufacturing; Medicine; Medicine & Public Health; Middle Aged; Neurotoxicity; Oncology; Patients; Pediatrics; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - immunology; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - therapy; Receptors, Chimeric Antigen - immunology; Safety; Sialic Acid Binding Ig-like Lectin 2 - immunology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Young Adult
• ISSN: 0887-6924; 1476-5551; 1476-5551
• DOI: 10.1038/s41375-024-02220-y

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.