10-year experience of CD22 CAR T-cells for children and young adults with B-cell acute lymphoblastic leukemia Open Access

• CD22 CAR T-cells demonstrated efficacy in a refractory population of children and young adults with B-ALL regardless of disease burden.

• Final analysis of this decade-long trial offers insight into IEC-HS management and CAR T-cell pharmacokinetics.

In 2014, the first patient received a CD22 chimeric antigen receptor (CAR) T-cell product. As one of the earliest approaches targeting an antigen other than CD19, this trial addressed an unmet need while providing insights into CAR T-cell efficacy, impact of manufacturing changes, and management of inflammatory toxicities over its 10-year span. This final chapter provides a comprehensive review of the collective findings. Across 78 patients with B-ALL who were infused, cytokine release syndrome (CRS) was seen in 66 (84.6%) patients, while 28 (35.9%) had immune effector cell-associated hemophagocytic lymphohistiocytosis (HLH)-like syndrome (IEC-HS) and 18 (23.1%) had reversible neurotoxicity. Complete response (CR) was achieved in 54 (70.1%) patients by Day 28, of whom 45 (83.3%) were measurable-residual disease (MRD) negative. Median OS was 13.6 months and median relapse free survival (RFS) was 6.1 months. Pharmacokinetics revealed peak CAR T-cell expansion at a median of 14 (range 12-50) days with no variation by dose. Interestingly, toxicities, CAR T-cell expansion, and disease response did not correlate with baseline disease burden. Additionally, while early intervention approaches to mitigate IEC-HS severity for this construct appeared promising, further study is needed. Given the critical importance of CD22 targeting, this experience serves as a foundation for new approaches targeting CD22 while providing ongoing support for dual-targeting approaches and insights into toxicity mitigation. NCT02315612