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Published on: February 17, 2022
Ten-year experience of CD22 CAR T cells for children and young adults with B-cell acute lymphoblastic leukemia
Alexandra Dreyzin1,2, Bonnie Yates1, Haneen N Shalabi1
1Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Abstract:
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-cell acute lymphoblastic leukemia who received infusion, cytokine release syndrome was observed in 66 (84.6%) patients, whereas 28 (35.9%) had immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS), and 18 (23.1%) had reversible neurotoxicity. Complete response was achieved in 54 (70.1%) patients by day 28, of whom 45 (83.3%) were measurable residual disease negative. Median overall survival was 13.6 months, and median relapse-free survival was 6.1 months. Pharmacokinetics revealed peak CAR T-cell expansion at a median of 14 days (range, 12-50), with no variation by dose. Interestingly, toxicities, CAR T-cell expansion, and disease response did not correlate with baseline disease burden. Additionally, although 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. This trial was registered at www.ClinicalTrials.gov as NCT02315612.
Insights
This 10-year study of CD22 CAR T-cell therapy in B-ALL patients showed significant complete response rates and provided crucial insights into managing toxicities and optimizing manufacturing for future treatments.
Area of Science:
- Immunology
- Oncology
- Cell Therapy
Background:
- CD22-targeted chimeric antigen receptor (CAR) T-cell therapy represents an early alternative to CD19-directed treatments for B-cell acute lymphoblastic leukemia (B-ALL).
- This 10-year study offers a comprehensive review of the first CD22 CAR T-cell product, addressing critical aspects of its clinical application.
Purpose of the Study:
- To comprehensively review collective findings from a decade of CD22 CAR T-cell therapy in B-ALL.
- To evaluate the efficacy, safety, and pharmacokinetic profile of CD22 CAR T-cell therapy.
- To provide insights into manufacturing changes and toxicity management for CD22-targeted approaches.
Main Methods:
- Analysis of data from 78 B-ALL patients infused with a CD22 CAR T-cell product over a 10-year period.
- Assessment of treatment response, including complete response (CR) and measurable residual disease (MRD) negativity.
- Evaluation of adverse events such as cytokine release syndrome (CRS), immune effector cell-associated hemophagocytic lymphohistiocytosis (IEC-HS), and neurotoxicity.
- Pharmacokinetic analysis of CAR T-cell expansion and correlation with clinical outcomes and toxicities.
Main Results:
- A complete response (CR) was achieved in 70.1% of patients by Day 28, with 83.3% of those being measurable residual disease (MRD) negative.
- High rates of toxicities were observed: 84.6% for cytokine release syndrome (CRS), 35.9% for immune effector cell-associated hemophagocytic lymphohistiocytosis (IEC-HS)-like syndrome, and 23.1% for reversible neurotoxicity.
- Median overall survival (OS) was 13.6 months, and median relapse-free survival (RFS) was 6.1 months. Peak CAR T-cell expansion occurred at a median of 14 days.
- No correlation was found between baseline disease burden and toxicities, CAR T-cell expansion, or disease response.
Conclusions:
- CD22 CAR T-cell therapy demonstrates significant efficacy in B-ALL, establishing a foundation for future CD22-targeted strategies.
- While toxicities like CRS and IEC-HS are common, early interventions show promise for mitigation, warranting further investigation.
- This extensive experience provides valuable insights for refining CD22-targeting approaches, dual-targeting strategies, and toxicity management in CAR T-cell therapy.
