Peer-influenced content. Sources you trust. No registration required. This is HCN.

The New England Journal of MedicineIndolent CD4+ CAR T-Cell Lymphoma after Cilta-cel CAR T-Cell Therapy

Identification and Characterization of Indolent CD4+ CAR T-Cell Lymphoma Post-CAR T-Cell Therapy: Potential Mechanisms and Clinical Implications

A 71-year-old woman developed an indolent CD4+ cytotoxic chimeric antigen receptor (CAR) T-cell lymphoma involving the small intestine after receiving ciltacabtagene autoleucel (cilta-cel) CAR T-cell therapy for multiple myeloma. This case highlights the importance of recognizing secondary malignancies post-CAR T-cell therapy and stresses the need for thorough molecular and genomic analysis to understand the underlying mechanisms.

Key Points:

  • Patient Background:
    • 71-year-old woman with an 8-year history of multiple myeloma.
    • Treated with cyclophosphamide–fludarabine lymphodepleting therapy followed by ciltacabtagene autoleucel (cilta-cel) CAR T-cell therapy targeting B-cell maturation antigen (BCMA).
    • Achieved complete response, negative for minimal residual disease (MRD).
  • Symptom Onset:
    • Four months post-CAR T-cell therapy, the patient presented with progressively worsening nonbloody diarrhea and weight loss of 5.4 kg.
  • Initial Laboratory and Diagnostic Findings:
    • Laboratory findings included abnormalities in serum bicarbonate, creatinine, and glomerular filtration rate.
    • Endoscopy revealed duodenal ulcerations initially interpreted as probable autoimmune enteropathy.
  • Molecular and Histopathological Analysis:
    • Biopsy of duodenal ulcer showed small lymphocytes with minimal atypia, indicative of probable autoimmune enteropathy.
    • Further biopsy and molecular analysis confirmed CD4+ cytotoxic CAR T-cell lymphoma.
    • Whole-genome sequencing identified a single lentiviral insertion site within the SSU72 gene and numerous genetic alterations.
  • Clinical Course and Treatment:
    • Initial treatment with intravenous methylprednisolone, oral budesonide, and IVIG showed improvement, but symptoms recurred after tapering glucocorticoids.
    • Continued treatment with mycophenolate mofetil was unsuccessful.
    • Transitioned to cyclophosphamide and teduglutide with ongoing total parenteral nutrition, showing mild improvement.
  • Molecular Findings:
    • High levels of CAR T-cell chimeric fusions confirmed CD4+ CAR T-cell presence in the tumor.
    • Identified multiple somatic copy-number variations and genetic alterations related to cancer and immune system genes.
    • The lentiviral vector carrying the anti-BCMA CAR T-cell cassette was integrated into the positive strand of the first chromosome at position 1,556,938, affecting the SSU72 gene.
  • Implications for Clinical Practice:
    • Recognition of secondary malignancies post-CAR T-cell therapy is crucial.
    • Thorough molecular and genomic analysis is essential for diagnosis and understanding the mechanisms of CAR T-cell-related lymphomagenesis.
    • Clinicians should be aware of the morphologic and immunophenotypic characteristics of CAR T-cell lymphoma when evaluating post-therapy complications.

In a recent study, researchers found that second primary malignancies were reported in 536 of 12,394 (4.3%) adverse events after CAR-T therapies in Adverse Event Reporting System (FAERS). Myeloid and T-cell neoplasms were disproportionately more frequent, with 208 reports of myelodysplasia and 106 reports of acute myeloid leukemias.

More on Genomics

The Healthcare Communications Network is owned and operated by IQVIA Inc.

Click below to leave this site and continue to IQVIA’s Privacy Choices form