Chimeric antigen receptor T cells can eradicate large burdens of multiple myeloma, according to a new study presented at ASH.
Chimeric antigen receptor (CAR) T cells can eradicate large burdens of multiple myeloma, according to a new study.
“For the first time, we have shown that CAR T cells targeting B-cell maturation antigen (BCMA) can eliminate multiple myeloma in humans,” said James N. Kochenderfer, MD, of the Center for Cancer Research at the National Cancer Institute in Bethesda, Maryland.
Dr. Kochenderfer presented the results (abstract LBA-1) at the 57th Annual American Society of Hematology (ASH) Meeting and Exposition, held December 5–8 in Orlando, Florida.
BCMA, a member of the tumor necrosis factor family, is a protein expressed by both normal and malignant plasma cells. “BCMA is uniformly expressed on 60% to 70% of cases of multiple myeloma. Because BCMA is only expressed by plasma cells and a small fraction of B cells, it is a promising target for treating multiple myeloma,” said Dr. Kochenderfer.
In this phase I clinical trial, Dr. Kochenderfer and colleagues extracted immune T cells from patients and genetically engineered the cells to express an anti-BCMA chimeric antigen receptor (CAR-BCMA) to recognize and kill the myeloma cells. Patients received one round of chemotherapy before their own engineered cells were infused back into their bodies at one of four dose levels.
As of November 2015, 11 patients with advanced multiple myeloma and a median of seven previous failed therapies have participated in the trial.
One month following infusion, the two patients treated at the highest dose level demonstrated the strongest anticancer responses. One patient achieved a stringent complete remission at 2 months following the CAR-BCMA T-cell infusion. “The patient was platelet transfusion-dependent for 9 weeks after infusion,” he said. “Multiple myeloma that made up more than 90% of the patient’s bone marrow cells was eliminated after CAR-BCMA infusion.”
The other patient had undetectable myeloma in the bone marrow plasma cells, but has not yet reached complete remission status.
Of the six patients treated on the lowest two dose levels, one patient experienced a short partial remission of 2 weeks and the other five remained stable.
Two patients on the second-highest dose level maintained stable disease, and one patient obtained a very good partial response.
Toxicity and side effects were mild for patients who received the lowest dose levels, he said. Patients who received the highest doses experienced cytokine release syndrome, a severe and potentially fatal side effect of therapy characterized by high fever, muscle pain, and heart and kidney problems.
Engineered CAR-BCMA T cells were detected in the blood of all 10 patients assessed to date. Toxicities were similar to those observed in leukemia patients treated with similar therapies, he noted.
“These findings suggest that CAR-BCMA is a promising option for advanced multiple myeloma patients who have failed several previous therapies,” Dr. Kochenderfer said. “Toxicity was substantial, but reversible, and similar to that seen on previous CAR T-cell trials.”
He believes that “anti-BCMA CAR T cells are a promising new therapy for multiple myeloma.”