Case report: Differential diagnosis of highly amplified anti-CD5 CAR T cells and relapsed lymphoma cells in a patient with refractory ALK positive anaplastic large cell lymphoma

Front Immunol. 2023 Dec 8:14:1280007. doi: 10.3389/fimmu.2023.1280007. eCollection 2023.

Abstract

Background: Anaplastic Large Cell Lymphoma (ALCL) is one of the most common subtypes of T-cell lymphoma. Among these, refractory and relapsed (r/r) ALK positive ALCL lacks effective therapies. The chimeric antigen receptor-modified T (CAR-T) cell therapy holds great promise as a therapeutic strategy for this disease. However, it is not known yet whether anti-CD5 CAR-T cells are sufficient for the definitive treatment of relapsed ALK+ ALCL, nor the role of accurate laboratory-based diagnoses during CAR-T treatment.

Case presentation: The adolescent patient received autologous T cells containing sequences encoding VH domains specific to CD5. Following the infusion, there was an increase in both the copy number and proportion of CAR-T cells in peripheral blood. IL-6 and ferritin levels in the patient exhibited significant fluctuations, with increases of 13 and 70 folds respectively, compared to baseline after the treatment. Additionally, adverse effects were observed, including grade 4 rash, grade 1 headache, nausea, and neck-pain. Surprisingly, a relapsed disease phenotype was identified based on the results of PET/CT and histopathological analysis of the inguinal lymph node biopsy. After conducting a thorough diagnostic assessment, which included flow cytometry, next-generation sequencing (NGS), examination of immune-related gene rearrangements, and analysis of the immune repertoire of T-cell receptors (TCR), we conclusively determined that the hyperplastic T cells identified in the lymph node were the result of an expansion of CAR-T cells. Ultimately, the patient has attained complete remission (CR) and has sustained a disease-free survival state for 815 days as of the cutoff date on August 30, 2023.

Conclusion: Taken together, the results demonstrate that anti-CD5 CAR-T cells can induce a clinical response in r/r ALK+ ALCL patient. Furthermore, this case underscores the importance of utilizing advanced technologies with high sensitivity and accuracy for biological detection in clinical laboratory diagnosis and prognosis in CAR-T cell treatment.

Trial registration number: NCT04767308.

Keywords: ALK-positive anaplastic large cell lymphoma; CD5 antigen; cell therapy; chimeric antigen receptor T cells; laboratory based differential diagnosis.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Diagnosis, Differential
  • Humans
  • Lymphoma, Large-Cell, Anaplastic* / drug therapy
  • Lymphoma, Large-Cell, Anaplastic* / therapy
  • Positron Emission Tomography Computed Tomography
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Chimeric Antigen* / genetics
  • Receptors, Chimeric Antigen* / therapeutic use
  • T-Lymphocytes / pathology

Substances

  • Receptor Protein-Tyrosine Kinases
  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen

Associated data

  • ClinicalTrials.gov/NCT04767308

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The study was sponsored by the National Natural Science Foundation of China (Grant No. 82270203 to Min Xiao and 82100247 to Wei Mu).