Scientists refine CAR T cell therapy for advanced lymphoma
Scientists have refined anti-CD19 chimeric antigen receptor (CAR) T cell therapy, an investigational treatment for advanced non-Hodgkin’s lymphoma, with initial results showing significantly higher response and survival rates than the standard repertoire.
One refinement involves the addition of low-dose conditioning chemotherapy with cyclophosphamide plus fludarabine prior to CAR T cell therapy to induce remission in patients with advanced lymphoma. [EHA 2016, abstract S792]
High-dose conditioning chemotherapy with cyclophosphamide (total dose, 60 or 120 mg/kg) plus fludarabine (25 mg/m2 daily for 3 days) was previously shown to increase the efficacy of subsequent anti-CD19 CAR T cell therapy. [J Clin Oncol 2015;33:540-549] However, there were concerns that the responses observed in the study might have been attributed to the high-dose cyclophosphamide given rather than to the CAR T cells.
“This prompted us to conduct another study to evaluate whether similar efficacy can be achieved with a lower dose of conditioning chemotherapy,” explained Dr. Stephanie Goff of the National Institutes of Health, Bethesda, MD, US, co-author of the present study.
Goff and colleagues recruited 19 patients with diffuse large B-cell lymphoma, one patient with mantle cell lymphoma and two patients with follicular lymphoma. The patients were treated with cyclophosphamide 300 or 500 mg/m2 daily plus fludarabine 30 mg/m2 daily for 3 days, followed by a single dose of CAR T cells infused 2 days after completion of chemotherapy.
“The overall response rate was 73 percent. Among 19 patients with diffuse large B-cell lymphoma, eight demonstrated complete response [CR], five had partial response, two had stable disease and the remaining four patients had disease progression. CR was also achieved in the patient with mantle cell lymphoma and the two patients with follicular lymphoma,” reported Goff. “The duration of response ranged from 1 to 20 months, with 10 ongoing remissions.”
Chemotherapy pretreatment resulted in significant increases in mean serum interleukin (IL)-15 levels from 4 pg/mL prior to administration of chemotherapy to 32 pg/mL after chemotherapy completion. Significant changes were also seen in the levels of IL-7, monocyte chemoattractant protein-1 and perforin.
The most commonly reported adverse events were neurotoxicities, fever and hypotension.
“The findings should help in refining how treatment with anti-CD19 CAR T cells can be best implemented,” concluded Goff.