A new study shows promise for patients with B-cell malignancies who receive allogeneic hematopoietic stem cell transplantation (alloHSCT). These blood malignancies include chronic lymphocytic leukemia (CLL), Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL Ph+), Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL Ph-neg), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), and also follicular lymphoma (FL).
Oftentimes, this patient population experiences very poor outcomes, leading to death following transplantation because the patient may relapse and/or experience graft-versus-host disease (GVHD). However, researchers at the National Cancer Institute Center for Cancer Research in Bethesda, Md, began looking at ways to address these deadly complications.
"We aim to improve the treatment of B-cell malignancies that progress after allogenic transplantation by infusing allogenic T cells that were genetically modified to express anti-CD19 chimeric antigen receptors," said presenter James N. Kochenderfer, MD, during the American Society of Hematology's 57th Annual Meeting in Orlando, Fla., December 5, 2015 (abstract 99). "In short, we are trying to genetically enhance the donor's own lymphoctyes to make the infusion of lymphoctyes more effective."
The research team conducted a clinical trial of allogeneic T cells that were genetically engineered to express a chimeric antigen receptor (CAR) targeting the B-cell antigen CD19. Patients with B-cell malignancies after alloHSCT received a single infusion of CAR T cells.
Dr. Kochenderfer emphasized that patients did not receive chemotherapy or other therapies during this trial. "When chemotherapy is not given, a higher dose of CAR T cells can be given with acceptable levels of toxicity," he said.
The T cells were obtained from each recipient’s alloHSCT donor, most of whom were siblings. Of these patients, one experienced GVHD, a potentially lethal allogeneic immune response, but continued to improve.
Of the 20 study participants, eight experienced remissions, including six complete remissions (CR) and two partial remissions. The response rate was highest for ALL patients, but responses also occurred in chronic lymphocytic leukemia (CLL) and lymphoma. The longest ongoing CR is over 30 months in a patient with CLL. No patient developed new-onset acute GVHD after CAR T cells were infused.
Patients with high tumor burdens experienced severe cytokine-release syndrome which caused fever, tachycardia, and hypotension.
Dr. Kochenderfer ended his presentation by reminding the audience that these were patients with very advanced malignancies, many of whom had experienced failure of standard therapies, but went on to allogeneic transplant therapy which is considered a last-chance therapy.