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

Leukemia. 2024 May;38(5):963-968. doi: 10.1038/s41375-024-02220-y. Epub 2024 Mar 15.

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.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Immunotherapy, Adoptive* / adverse effects
  • Immunotherapy, Adoptive* / methods
  • Male
  • Middle Aged
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma* / immunology
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma* / therapy
  • Receptors, Chimeric Antigen* / immunology
  • Sialic Acid Binding Ig-like Lectin 2* / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Young Adult

Substances

  • Sialic Acid Binding Ig-like Lectin 2
  • CD22 protein, human
  • Receptors, Chimeric Antigen