Photo by Robert Hood / Fred Hutch News Service
Many patients with late-stage blood cancers receiving an experimental T-cell therapy went into complete remission, according to preliminary research results from a Fred Hutchinson Cancer Research Center trial presented this week at the annual meeting of the American Society of Hematology.
“It’s an extraordinary time, not just for us but for everybody working in this field,” said Dr. Cameron Turtle, a clinical researcher at Fred Hutch, who presented the findings. “These are responses that you just don’t expect to see with chemotherapy alone in these patients.”
Immunotherapy, such as in this T-cell trial, harnesses the body’s own immune system to fight disease. One subset of this trial enrolls 30 adult patients with advanced B-cell acute lymphoblastic leukemia, or ALL. The other includes 32 adult participants with B-cell non-Hodgkin lymphoma and 9 with chronic lymphocytic leukemia, or CLL.
Outside of this trial, which is ongoing, participants all had very few conventional treatment options available to them, Turtle said.
The trial is funded by Juno Therapeutics, which was founded by Fred Hutch, Memorial Sloan-Kettering Cancer Center and Seattle Children’s Research Institute to commercialize promising immunotherapies developed by researchers at the three institutions.
Researchers insert an engineered receptor (called a CAR) into patients’ own immune cells, which allows these T cells to recognize and kill cancer cells bearing a marker called CD19. Patients are infused with specific amounts of two kinds of CAR T cells: CD4 (“helper”) T cells and CD8 (“killer”) T cells.
Using a defined composition of T cells is a relatively new strategy in CAR T-cell immunotherapy that was developed at the Hutch. Few other research groups have taken this approach, Turtle said. The idea is that the two types of cells will work together to kill cancer more effectively.
Of the 29 ALL patients whose disease could be evaluated after CAR T-cell treatment, 27 of them (93 percent) achieved a complete remission of their disease in their bone marrow — meaning that no traces of their cancer could be found in the marrow where the cancer is concentrated. The researchers are currently evaluating how long these remissions are lasting.
“For this group of patients, you would not expect a complete remission rate anywhere near 93 percent with conventional chemotherapy,” Turtle said.
Among the non-Hodgkin lymphoma participants, the treatment initially caused tumors to shrink in half of patients (50 percent rate of response). This was because patients’ immune systems were rejecting some CAR T cells. To minimize those effects, the team added an additional chemotherapy drug before T-cell infusion, and saw dramatically increased CAR-T cell multiplication and persistence. Of the 11 non-Hodgkin lymphoma patients who received both the improved chemotherapy and optimized T-cell dosing, the response rate was 82 percent. Sixty-four percent went into complete remission.
The information Turtle presented at ASH included additional patients not reflected in the published abstracts.
The additional pre-infusion chemotherapy seemed to make a difference in the ALL trial as well, the researchers reported. In ALL patients who received the second chemotherapy drug, the CAR T-cells multiplied in greater numbers and persisted longer. These patients so far also appear to be surviving longer without signs of their disease coming back.
The researchers found that the T-cell dosing was important for patient outcomes. In the ALL trial, the team found that an inverse-dosing strategy — giving the lowest doses of T cells to the patients with the highest tumor burdens — reduced the risks of serious side effects.
“If you get the type of chemotherapy right and the dose right, you have much better outcomes with excellent response rates and less toxicity,” Turtle said.
Turtle said that he feels optimistic for the next phases of this research based on these results.
“We’ve got many ideas on how to move forward, and I’m hopeful that those ideas are going to progressively improve responses and make the treatment better for patients.”
The study team comprises researchers at Fred Hutch, University of Washington and Seattle Children’s Research Institute. Turtle and Dr. David Maloney, also of Fred Hutch, lead the trials. The research team also includes Fred Hutch faculty members Drs. Stanley Riddell, Michael Jensen and Shelly Heimfeld. Riddell and Jensen are two of Juno’s scientific founders.
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Susan Keown is a staff writer at Fred Hutchinson Cancer Research Center. Before joining Fred Hutch in 2014, Susan wrote about health and research topics for a variety of research institutions, including the National Institutes of Health and the Centers for Disease Control and Prevention. Reach her at firstname.lastname@example.org or follow her on Twitter at @sejkeown.
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