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

On 24^th 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.