The use of therapy with chimeric antigen receptor (CAR)-modified T-cells consistently demonstrated activity in advanced hematologic malignancies, including different types of lymphoma, in multiple trials reported at ASH 2015.
In one trial, disease remission persisted for as long as 36 months in 8 of 20 patients who were treated for hematologic malignancies at the National Cancer Institute (NCI). The 40% overall response rate included 4 of 5 patients with treatment-refractory acute lymphoblastic leukemia (ALL).
All the patients in the trial received a single infusion of donor T-cells modified by the addition of anti-CD19 CAR, and none of the patients received chemotherapy. The treatment led to severe tumor lysis syndrome in some patients, which was manageable with conventional interventions.
“We have treated patients with very advanced malignancies, including some patients who failed all standard therapies and continued to progress after allogeneic stem-cell transplantation, a last-chance therapy for these types of patients,” said James Kochenderfer, MD, an investigator in the experimental transplantation and immunology branch of the NCI’s Center for Cancer Research.
The remaining 15 patients consisted of 5 each with chronic lymphocytic leukemia, mantle-cell lymphoma (MCL), and diffuse large B-cell lymphoma (DLBCL). In each disease group, ≥1 patients responded to the therapy, said Dr Kochenderfer.
Some patients, such as 1 patient with high-burden DLBCL, have had dramatic responses, including large tumors involving the cranium and an orbital cavity. All evidence of the disease disappeared within 5 days of the CAR T-cell infusion.
The University of Pennsylvania has one of the most active CAR T-cell clinical programs in the country, and investigators reported findings from ongoing trials of patients with non-Hodgkin lymphoma (NHL) and ALL.
CAR T-cells–based agents are an emerging treatment approach for NHL, and Penn researchers reported objective responses in 15 of 28 patients treated to date with the investigational anti-CD19 CAR T-cells agent known as CTL019. All but 1 of the responses were complete remissions.
The overall responses consisted of those in 8 of 11 patients with follicular lymphoma, in 7 of 15 patients with DLBCL, and in 1 of 2 patients with MCL.
All 28 patients were refractory to conventional therapies, including some who had progressive disease after stem-cell transplantation. The median progression-free survival in the patients with follicular lymphoma and in those with DLBCL had yet to be reached after a median follow-up of >14 months.
“Our early results in this trial provide increasing evidence for the role of personalized cellular therapies in patients with NHL,” said Stephen J. Schuster, MD, Robert and Margarita Louis-Dreyfus Associate Professor in Chronic Lymphocytic Leukemia and Lymphoma Clinical Care and Research at Penn Medicine’s Abramson Cancer Center, Philadelphia.