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Patients with advanced lymphoma in remission after T-cell therapy

Patients who received a dose of CD19 targeted defined composition engineered T cells after chemotherapy went into complete remission

Date:
September 7, 2016
Source:
Fred Hutchinson Cancer Research Center
Summary:
Data has been released 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.
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Dr. Cameron Turtle, one of the study leaders.
Credit: Fred Hutch file

In a paper published in Science Translational Medicine, 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 percent 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 percent complete response rate in patients who received JCAR014 plus cyclophosphamide-based chemotherapy without fludarabine. 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 percent (9/11)
  • Complete Response rate: 64 percent (7/11)
  • Severe Cytokine Release Syndrome: 9 percent (1/11)
  • Severe neurotoxicity: 18 percent (2/11)

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.

"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.

For Juno Therapeutics (NASDAQ: JUNO), these insights from the JCAR014 study are key to its development of JCAR017, a similar product candidate for the treatment of CD19 positive blood cancers. Like JCAR014, JCAR017 uses a one-to-one ratio of helper and killer CAR T cells, and the company believes it has the potential to be a "best-in-class" treatment for non-Hodgkin lymphoma, chronic lymphocytic leukemia, and adult and pediatric acute lymphoblastic leukemia. JCAR017 is currently in a phase I, multi-center study.

"We are encouraged by the efficacy and duration of response that we are seeing with defined composition CAR T treatment in patients with lymphoma and other B-cell malignancies," said Mark J. Gilbert, Juno's Chief Medical Officer. "We hope that the insights from JCAR014 will make it possible to bring more life-saving treatments to more patients with blood cancers."


Story Source:

Materials provided by Fred Hutchinson Cancer Research Center. Note: Content may be edited for style and length.


Journal Reference:

  1. C. J. Turtle, L.-A. Hanafi, C. Berger, M. Hudecek, B. Pender, E. Robinson, R. Hawkins, C. Chaney, S. Cherian, X. Chen, L. Soma, B. Wood, D. Li, S. Heimfeld, S. R. Riddell, D. G. Maloney. Immunotherapy of non-Hodgkins lymphoma with a defined ratio of CD8 and CD4 CD19-specific chimeric antigen receptor-modified T cells. Science Translational Medicine, 2016; 8 (355): 355ra116 DOI: 10.1126/scitranslmed.aaf8621

Cite This Page:

Fred Hutchinson Cancer Research Center. "Patients with advanced lymphoma in remission after T-cell therapy: Patients who received a dose of CD19 targeted defined composition engineered T cells after chemotherapy went into complete remission." ScienceDaily. ScienceDaily, 7 September 2016. <www.sciencedaily.com/releases/2016/09/160907215218.htm>.
Fred Hutchinson Cancer Research Center. (2016, September 7). Patients with advanced lymphoma in remission after T-cell therapy: Patients who received a dose of CD19 targeted defined composition engineered T cells after chemotherapy went into complete remission. ScienceDaily. Retrieved May 26, 2017 from www.sciencedaily.com/releases/2016/09/160907215218.htm
Fred Hutchinson Cancer Research Center. "Patients with advanced lymphoma in remission after T-cell therapy: Patients who received a dose of CD19 targeted defined composition engineered T cells after chemotherapy went into complete remission." ScienceDaily. www.sciencedaily.com/releases/2016/09/160907215218.htm (accessed May 26, 2017).

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