Patients With Advanced Lymphoma in Remission After T-Cell Therapy

Researchers evaluate chimeric antigen receptor (CAR) T-cell treatment

In a paper published in Science Translational Medicine, researchers at the Fred Hutchinson Cancer Research Center have reported data from an early-phase study of patients with advanced non-Hodgkin’s lymphoma (NHL) who received JCAR014 (Juno Therapeutics), a chimeric antigen receptor (CAR) T-cell treatment, and chemotherapy. CAR T cells consist of the patient’s own immune cells that are genetically engineered to better-identify and kill cancer cells.

The paper reported results from the first 32 patients in a dose-finding trial of JCAR014 after a round of chemotherapy called lymphodepletion, which is designed to create a more-favorable environment for the CAR T cells to grow in the patient’s body. Key findings of the study demonstrated the importance of the choice of the lymphodepletion regimen and the effects of different doses of CAR T cells.

Half of the 18 patients who were evaluable for efficacy after receiving CAR T cells and the chemotherapy agents fludarabine and cyclophosphamide (Cy/Flu) experienced a complete response, which compared favorably with the 8% complete response rate in patients who received JCAR014 plus cyclophosphamide-based chemotherapy without fludarabine.

Dose-limiting toxicities were observed in some patients who received the highest CAR T-cell dose. The study is continuing with the intermediate CAR T-cell dose.

In patients who received Cy/Flu lymphodepletion and the intermediate dose of JCAR014, the data showed a promising early efficacy and adverse event profile. Specifically:

  • Overall response rate: 82% (9/11)
  • Complete response rate: 64% (7/11)
  • Severe cytokine release syndrome: 9% (1/11)
  • Severe neurotoxicity: 18% (2/11)

JCAR014 uses a 1:1 ratio of helper (CD4+) and killer (CD8+) CAR T cells, which join forces to kill tumor cells that produce CD19, a molecule found on the surface of many blood cancer cells, including lymphoma and leukemia. The study data suggested that with a defined one-to-one composition of cells, treatment efficacy is increased while toxic effects are minimized.

Source: Juno Therapeutics; September 7, 2016.