CAR T-cell therapy for leukemia leads to remissions in clinical trial
In an early-phase clinical trial of an experimental immunotherapy, researchers achieved durable molecular remissions in patients with chronic lymphocytic leukemia who had failed other treatments
Fred Hutchinson Cancer Research Center
SEATTLE — July 17, two thousand seventeen — Researchers at Fred Hutchinson Cancer Research Center showcased about seventy percent of patients with the most common adult leukemia had their tumors shrink or vanish following an experimental chimeric antigen receptor (CAR) T-cell immunotherapy.
The researchers also found that measuring genetic traces of cancer cells taken from bone marrow biopsies might be a better indicator of prognosis than the standard lymph knot scan.
The Journal of Clinical Oncology published the results online July seventeen of the Phase 1/Two clinical trial, which included twenty four patients with chronic lymphocytic leukemia (CLL) who had failed other treatments. Most of the patients had seen their cancer progress despite treatment with ibrutinib, a targeted cancer drug approved in two thousand fourteen for CLL by the U.S. Food and Drug Administration.
This history placed them in a high-risk group that was found in previous studies to have brief survival with standard therapies.
“It was not known whether CAR T-cells could be used to treat these high risk CLL patients,” said lead author Dr. Cameron Turtle, an immunotherapy researcher at Fred Hutch. “Our investigate shows that CD19 CAR T-cells are a very promising treatment for CLL patients who have failed ibrutinib.”
CD19 CAR T-cells are a type of immunotherapy in which a patient’s T cells are extracted from their blood and modified in a lab to recognize CD19, a target on the surface of leukemia cells. The engineered T cells are then infused back into the patient where they multiply and hunt down and kill cancer cells.
In CLL, bone marrow makes too many abnormal lymphocytes, which are a type of white blood cell. The American Cancer Society estimates that in the U.S., there will be about 20,000 fresh cases and Four,600 deaths from CLL in 2017. Tests of blood, bone marrow and lymph nodes–where lymphocytes congregate to fight infection–reveal the disease.
The twenty four patients participating in the examine ranged in age from forty to seventy three years, with a median age of 61. They had received a median of five other therapies with as few as three and as many as nine.
Researchers found that seventeen out of twenty four (71 percent) of patients witnessed their tumors shrink or vanish following CAR T-cell therapy using the standard measure of lymph knot size by CT scans four weeks after treatment.
Of side effects of CAR-T cell therapy, twenty of the twenty four patients–83 percent–experienced cytokine release syndrome (grade 1-2, eighteen patients; grade Four, one patient; grade Five, one patient) and eight patients (33 percent) developed neurotoxicity (grade Three, five patients; grade Five, one patient). For the most part the side effects were reversible, but two patients had side effects severe enough to require being admitted to the intensive care unit and one of those patients died.
(An earlier report on trial results was introduced by Turtle in December at the American Society of Hematology annual meeting.)
The fresh paper expands on the measures used to indicate whether the CAR T-cell treatment is working.
To take a closer look to see if any cancer cells remained after treatment, the research team analyzed samples taken from some of the patients’ bone marrow four weeks after the CAR T-cell infusion. The team used a genetic test called IGH deep sequencing, which is akin to a bar code and enables researchers to track cancer cells in the bod.
Turtle and his collaborators did the sequencing analysis in twelve of the patients. Seven of the twelve patients had no malignant copies. All patients without malignant copies were alive and free of disease at a median follow-up of 6.6 months after CAR T-cell infusion.
Compared with the CT scans, having no malignant gene sequences in bone marrow following CAR T-cell therapy was a better predictor of the cancer staying at bay–known as “progression-free survival,” the researchers found.
The probe is the very first to suggest that deep sequencing might be a superior measure for predicting outcomes four weeks after CAR T-cell therapy for CLL.
The immunotherapy team at Fred Hutch is still enrolling eligible patients with CLL, acute lymphoblastic leukemia and non-Hodgkin lymphoma for treatment on CD19 CAR T-cell trials. The patients are seen at Seattle Cancer Care Alliance, the clinical care playmate for Fred Hutch.
Fred Hutch co-authors of the paper are Kevin Hay, Laila-Aicha Hanafi, Shelly Heimfeld, Stanley R. Riddell and David G. Maloney. Other co-authors are Daniel Li, Juno Therapeutics; Sindhu Cherian, Xueyan Chen and Brent Wood, University of Washington; and Arletta Lozanski and John C. Byrd, The Ohio State University.
Funding for the project came from Juno Therapeutics, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, Life Science Discovery Fund, the Bezos family, and the University of British Columbia.
Turtle, Maloney and Riddell receive research funding from Juno Therapeutics and are named as inventors on one or more patents or patent applications related to this work. Riddell is a co-founder of Juno Therapeutics and has equity interest in Juno Therapeutics. Li is an employee of and has equity interests in Juno Therapeutics. Fred Hutch receives research funding from Juno Therapeutics.
At Fred Hutchinson Cancer Research Center, home to three Nobel laureates, interdisciplinary teams of world-renowned scientists seek fresh and innovative ways to prevent, diagnose and treat cancer, HIV/AIDS and other life-threatening diseases. Fred Hutch’s pioneering work in bone marrow transplantation led to the development of immunotherapy, which harnesses the power of the immune system to treat cancer. An independent, nonprofit research institute based in Seattle, Fred Hutch houses the nation’s very first cancer prevention research program, as well as the clinical coordinating center of the Women’s Health Initiative and the international headquarters of the HIV Vaccine Trials Network.
Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.
CAR T-cell therapy for leukemia leads to remissions in clinical trial, EurekAlert! Science News
CAR T-cell therapy for leukemia leads to remissions in clinical trial
In an early-phase clinical trial of an experimental immunotherapy, researchers achieved durable molecular remissions in patients with chronic lymphocytic leukemia who had failed other treatments
Fred Hutchinson Cancer Research Center
SEATTLE — July 17, two thousand seventeen — Researchers at Fred Hutchinson Cancer Research Center displayed about seventy percent of patients with the most common adult leukemia had their tumors shrink or vanish following an experimental chimeric antigen receptor (CAR) T-cell immunotherapy.
The researchers also found that measuring genetic traces of cancer cells taken from bone marrow biopsies might be a better indicator of prognosis than the standard lymph knot scan.
The Journal of Clinical Oncology published the results online July seventeen of the Phase 1/Two clinical trial, which included twenty four patients with chronic lymphocytic leukemia (CLL) who had failed other treatments. Most of the patients had seen their cancer progress despite treatment with ibrutinib, a targeted cancer drug approved in two thousand fourteen for CLL by the U.S. Food and Drug Administration.
This history placed them in a high-risk group that was found in previous studies to have brief survival with standard therapies.
“It was not known whether CAR T-cells could be used to treat these high risk CLL patients,” said lead author Dr. Cameron Turtle, an immunotherapy researcher at Fred Hutch. “Our investigate shows that CD19 CAR T-cells are a very promising treatment for CLL patients who have failed ibrutinib.”
CD19 CAR T-cells are a type of immunotherapy in which a patient’s T cells are extracted from their blood and modified in a lab to recognize CD19, a target on the surface of leukemia cells. The engineered T cells are then infused back into the patient where they multiply and hunt down and kill cancer cells.
In CLL, bone marrow makes too many abnormal lymphocytes, which are a type of white blood cell. The American Cancer Society estimates that in the U.S., there will be about 20,000 fresh cases and Four,600 deaths from CLL in 2017. Tests of blood, bone marrow and lymph nodes–where lymphocytes congregate to fight infection–reveal the disease.
The twenty four patients participating in the probe ranged in age from forty to seventy three years, with a median age of 61. They had received a median of five other therapies with as few as three and as many as nine.
Researchers found that seventeen out of twenty four (71 percent) of patients spotted their tumors shrink or vanish following CAR T-cell therapy using the standard measure of lymph knot size by CT scans four weeks after treatment.
Of side effects of CAR-T cell therapy, twenty of the twenty four patients–83 percent–experienced cytokine release syndrome (grade 1-2, eighteen patients; grade Four, one patient; grade Five, one patient) and eight patients (33 percent) developed neurotoxicity (grade Trio, five patients; grade Five, one patient). For the most part the side effects were reversible, but two patients had side effects severe enough to require being admitted to the intensive care unit and one of those patients died.
(An earlier report on trial results was introduced by Turtle in December at the American Society of Hematology annual meeting.)
The fresh paper expands on the measures used to indicate whether the CAR T-cell treatment is working.
To take a closer look to see if any cancer cells remained after treatment, the research team analyzed samples taken from some of the patients’ bone marrow four weeks after the CAR T-cell infusion. The team used a genetic test called IGH deep sequencing, which is akin to a bar code and enables researchers to track cancer cells in the bod.
Turtle and his collaborators did the sequencing analysis in twelve of the patients. Seven of the twelve patients had no malignant copies. All patients without malignant copies were alive and free of disease at a median follow-up of 6.6 months after CAR T-cell infusion.
Compared with the CT scans, having no malignant gene sequences in bone marrow following CAR T-cell therapy was a better predictor of the cancer staying at bay–known as “progression-free survival,” the researchers found.
The examine is the very first to suggest that deep sequencing might be a superior measure for predicting outcomes four weeks after CAR T-cell therapy for CLL.
The immunotherapy team at Fred Hutch is still enrolling eligible patients with CLL, acute lymphoblastic leukemia and non-Hodgkin lymphoma for treatment on CD19 CAR T-cell trials. The patients are seen at Seattle Cancer Care Alliance, the clinical care playmate for Fred Hutch.
Fred Hutch co-authors of the paper are Kevin Hay, Laila-Aicha Hanafi, Shelly Heimfeld, Stanley R. Riddell and David G. Maloney. Other co-authors are Daniel Li, Juno Therapeutics; Sindhu Cherian, Xueyan Chen and Brent Wood, University of Washington; and Arletta Lozanski and John C. Byrd, The Ohio State University.
Funding for the project came from Juno Therapeutics, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, Life Science Discovery Fund, the Bezos family, and the University of British Columbia.
Turtle, Maloney and Riddell receive research funding from Juno Therapeutics and are named as inventors on one or more patents or patent applications related to this work. Riddell is a co-founder of Juno Therapeutics and has equity interest in Juno Therapeutics. Li is an employee of and has equity interests in Juno Therapeutics. Fred Hutch receives research funding from Juno Therapeutics.
At Fred Hutchinson Cancer Research Center, home to three Nobel laureates, interdisciplinary teams of world-renowned scientists seek fresh and innovative ways to prevent, diagnose and treat cancer, HIV/AIDS and other life-threatening diseases. Fred Hutch’s pioneering work in bone marrow transplantation led to the development of immunotherapy, which harnesses the power of the immune system to treat cancer. An independent, nonprofit research institute based in Seattle, Fred Hutch houses the nation’s very first cancer prevention research program, as well as the clinical coordinating center of the Women’s Health Initiative and the international headquarters of the HIV Vaccine Trials Network.
Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.