Complete response for lymphoma patients with T-cell therapy7 Sep 2016
In a new paper, researchers from Fred Hutchinson Cancer Research Center shared data from an early-phase study of patients with advanced non-Hodgkin lymphoma (NHL) who received JCAR014, a Chimeric Antigen Receptor (CAR) T cell treatment, and chemotherapy. CAR T cells are made from a patient's own immune cells that are then genetically engineered to better identify and kill cancer cells.
The paper reported the results of the first 32 patients in a dose-finding trial of JCAR014 following a round of chemotherapy, called lymphodepletion, 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 lymphodepletion regimen and the effects of different doses of CAR T cells. 50 % of the 18 patients who were evaluable for efficacy after receiving CAR T cells and chemotherapy agents fludarabine and cyclophosphamide (Cy/Flu) had a complete response, which compares favorably to the 8 % complete response rate in patients who received JCAR014 plus cyclophosphamide-based chemotherapy without fludarabine.
Detailed clinical results: 64 % complete response rate
As previously reported, dose-limiting toxicities were observed in some patients in this dose-finding study who received the highest CAR T-cell dose. The study continues with the intermediate CAR T-cell dose. In patients that received Cy/Flu lymphodepletion and the intermediate dose of JCAR014, the data showed a promising early efficacy and side effect profile. Specifically:
- Overall Response rate: 82 %
- Complete Response rate: 64 %
- Severe Cytokine Release Syndrome: 9 %
- Severe neurotoxicity: 18 %
JCAR014's hallmark is its use of a one-to-one 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. By controlling the mixture of T cells that patients receive, the researchers can see relationships between cell doses and patient outcomes that were previously elusive. The data also suggest that with a defined one-to-one composition of cells, efficacy of treatment is increased, while toxic side effects are minimized.
The data will help the physicians personalize the treatment to each patient
"With the defined composition treatment, we are able to get more reproducible data about the effects of the cells -- both the beneficial impact against the cancer and any side effects to the patient," said Fred Hutch clinical researcher Dr. Stan Riddell, one of the senior authors of the paper, along with Dr. David Maloney. "We are then able to adjust the dose to improve what we call the therapeutic index -- impact against the tumor, with lower toxicity to the patient."
"This study shows that at the right dose of CAR T cells and lymphodepletion, we can achieve very good response rates for NHL patients who have no other treatment options," said Dr. Cameron Turtle, an immunotherapy researcher at Fred Hutch and one of the study leaders.
Source: Science Daily