Case Study Identifies New Trigger for CAR-T Cell Expansion in DLBCL in JCAR017 Trial

Chimeric antigen receptor (CAR)-T cells can re-expand in a patient months after the initial infusion and can also be active against the patient’s cancer. These are the findings of a single case study that was recently published in the New England Journal of Medicine.

In their correspondence to the journal, researchers from the Massachusetts General Hospital reported on the case of a 68-year old woman with refractory diffuse large—B-cell lymphoma with a BCL2 rearrangement and overexpressing MYC and BCL6. She had undergone 5 lines of treatment, including intensive infusional chemotherapy consisting of dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine and prednisone plus rituximab. One of the treatments also included intermediate-intensity allogeneic stem-cell transplantation.

Her disease was refractory to all 5 lines of treatment, after which she was enrolled in a trial of JCAR017, a CD19-directed CAR-T treatment. The patient was free of graft-versus host disease (GVHD) and was not on immunosuppressive treatment when she was enrolled. A new brain lesion was diagnosed at the time of her enrollment.

Following lymphodepleting fludarabine—cyclophosphamide, the women was infused with JCAR017. She did not exhibit cytokine release syndrome, neurotoxicity, or GVHD following the infusion—typical adverse effects associated with CAR-T treatment.

A subsequent scan 1 month after the JCAR017 infusion showed complete remission of the brain lesion, but restaging after 2 months showed subcutaneous disease, which was resected with incisional therapy.

Pharmacokinetic testing showed significant expansion of CAR-T cells. The woman’s central nervous system response was durable and she remained in remission at 12 months after treatment, which means CAR-T cells can cross the blood-brain barrier.

The authors write that re-expansion of the CAR-T cells was in response to the biopsy procedure conducted in the patient, when the presence of tumor cells alone were not sufficient to stimulate a response.

Reference

Abramson JS, McGree B, Noyes S, et al. Anti-CD19 CAR T cells in CNS diffuse large-B-cell lymphoma. N Engl J Med. 2017;377:783-784. doi: 10.1056/NEJMc1704610.