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Early Results From Juno's CAR-T Cell Therapy Promising in NHL


An early-phase, dose-finding study using a defined composition of chimeric antigen receptor-T cells, in patients with non-Hodgkin lymphoma, shows promise.

Controversial, yet very promising—chimeric antigen receptor (CAR)-T cells are proving to be a mixed bag. Results from an early-phase study conducted by researchers at the Fred Hutchison Cancer Research Center, published in Science Translational Research, showed that patients with advanced non-Hodgkin lymphoma (NHL), who were administered the appropriate regimen of JCAR014 (a CAR-T product developed by Juno Therapeutics) following chemotherapy, went into complete remission.

Thirty-two patients with relapsed/refractory NHL (22 to 70 years of age) were recruited to participate in a dose-finding trial, and underwent leukapheresis for CD19 CAR-T cell manufacturing. All the patients had measurable disease in lymph nodes or other extramedullary sites—9 had bone marrow disease and 1 had lymphoma in the cerebrospinal fluid.

One of the study objectives was to identify a manufacturing procedure for a consistent CD19 CAR-T cell product from the NHL patients, by selecting for CD8+ and CD4+ T cell subsets, the authors wrote. Patients were administered CD19 CAR-T cells in a 1:1 CD4+/ CD8+ ratio of CAR-T cells following treatment with cyclophosphamide (the chemotherapy), with or without fludarabine (Cy/Flu).

In July this year, the company was under fire following 2 deaths reported in patients with B cell acute lymphoblastic leukemia who had participated in the ROCKET trial. The FDA halted the trial; meanwhile Juno figured out that the drug fludarabine, introduced in the preconditioning regimen, could have been responsible for the deaths. The trial was subsequently resumed.

Of the 18 patients who were evaluable following this treatment, 50% had a complete response (CR), compared with a 8% CR in patients who did not receive fludarabine. Patients who received the maximum tolerated dose of CAR-T cells presented with dose-limiting toxicities. Among patients who were administered an intermediate dose, the following results were reported:

  • Overall response rate: 82%
  • CR rate: 64%
  • Severe cytokine release syndrome: 9%
  • Severe neurotoxicity: 18%

“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," senior author Stanley Riddell, MD, said in a statement. "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.”

Juno’s chief medical officer Mark J. Gilbert, MD, added that he’s encouraged by these results. “We hope that the insights from JCAR014 will make it possible to bring more life-saving treatments to more patients with blood cancers,” he said.


Turtle CJ, Hanafi L, Berger C, et al. Immunotherapy of non-Hodgkin’s lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor—modified T cells [published online September 7, 2016]. Sci Transl Med. 2016;8(355):355ra116.

doi: 10.1126/scitranslmed.aaf8621.

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