DLBCL

Published case study – Primary refractory DLBCL with brain parenchyma achieving complete remission with CAR T-cell therapy

On 24th August 2017, in a Letter to the Editor of the New England Journal of Medicine, Jeremy S. Abramson from Massachusetts General Hospital Cancer Center, Boston, MA, USA, et al. published a case report of a female patient, 68 years of age, with Diffuse Large B-Cell Lymphoma (DLBCL) refractory to intensive infusional chemotherapy, DA-EPOCH-R, and four other lines of treatment, including an intermediate-intensity allogeneic Stem Cell Transplant (allo-SCT) from an 8/8 HLA-matched unrelated donor.

Key Highlights:
  • Germinal center subtype, BCL2 rearrangement, multiple copies of MYC and BCL6
  • Enrolled in a phase I clinical trial of JCAR017 (NCT02631044); received lymphodepleting fludarabine–cyclophosphamide before CAR T-cell therapy
  • No CRS, neurotoxic effects, or GvHD
  • One month later, brain MRI confirmed complete remission
  • Two months later, restaging identified recurrent subcutaneous disease
  • After incisional biopsy, visible tumor receded with no further treatment
  • PET-CT 1 month after biopsy confirmed complete remission
  • Pharmacokinetic testing showed marked expansion of CAR T-cells
  • Ongoing remission at 12 months

The authors emphasized that they identified anti-CD19 CAR T-cells in cerebrospinal fluid, which confirms the ability of cells to cross the blood-brain barrier. Lastly, this case also confirms the ability of anti-CD19 CAR T-cells to re-expand in vivo months after initial infusion and can re-exert their anti-tumor activity; something in the biopsy procedure triggered CAR T-cell re-expansion and activation.

Abstract:

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References
  1. Abramson J.S. et al. Anti-CD19 CAR T Cells in CNS Diffuse Large-B-Cell Lymphoma. New England Journal of Medicine. 2017 Aug 24;377(8):783-784. DOI: 10.1056/NEJMc1704610.