An infusion of chimeric antigen receptor (CAR) T-cell therapy following chemotherapy can elicit responses in patients with non-Hodgkin lymphoma, a small study suggests.
However, patients also experienced significant acute toxicities, including fever, low blood pressure, focal neurological deficits, and delirium.
James N. Kochenderfer, MD, of the National Institutes of Health in Bethesda, Maryland, and his colleagues reported these results in the Journal of Clinical Oncology.
The trial was sponsored by the National Cancer Institute, but the CAR T-cell therapy being tested uses the same CAR construct as KTE-C19, which is being developed by Kite Pharma, Inc.
The study included 15 patients with advanced B-cell malignancies. The patients first received conditioning with cyclophosphamide and fludarabine.
A day later, they received a single infusion of the CAR T-cell therapy, which consists of T cells taken from each patient’s peripheral blood and modified to target CD19.
The researchers noted that the conditioning regimen is known to be active against B-cell malignancies and could have made a direct contribution to patient responses.
Response rates
Thirteen patients were evaluable for response. One patient was lost to follow-up because of noncompliance, and 1 died soon after treatment. The researchers said the cause of death was likely cardiac arrhythmia.
The overall response rate was 92%. Eight patients achieved a complete response (CR), and 4 had a partial response (PR).
Of the 7 patients with chemotherapy-refractory diffuse large B-cell lymphoma, 4 achieved a CR, 2 achieved a PR, and 1 had stable disease. Three of the CRs are ongoing, with the duration ranging from 9 months to 22 months.
Of the 4 patients with chronic lymphocytic leukemia, 3 had a CR, and 1 had a PR. All 3 CRs are ongoing, with the duration ranging from 14 months to 23 months.
Among the 2 patients with indolent lymphomas, 1 achieved a CR, and 1 had a PR. The duration of the ongoing CR is 11 months.
Toxicity
As seen in other studies, the CAR T-cell therapy was associated with fever, low blood pressure, focal neurological deficits, and delirium. Toxicities largely occurred in the first 2 weeks after infusion.
All but 2 patients experienced grade 3/4 adverse events. Four patients had grade 3/4 hypotension.
All patients had elevations in serum interferon gamma and/or IL-6 around the time of peak toxicity, but most did not develop elevations in serum tumor necrosis factor.
Neurologic toxicities included confusion and obtundation, which have been reported in previous studies. However, 3 patients developed unexpected neurologic abnormalities.
One of these patients developed aphasia on day 5 after CAR T-cell infusion. It occurred intermittently for 7 days before resolving. The patient also experienced right-sided facial paresis that lasted approximately 20 minutes on day 8 after infusion.
Another patient developed aphasia 5 days after CAR T-cell infusion, but this was followed by confusion and severe generalized myoclonus. All symptoms resolved by 11 days after the infusion, except for a mild tremor that resolved over the next month.
A third patient developed aphasia 5 days after CAR T-cell infusion. This was followed by confusion, hemifacial spasms, apraxia, and gait disturbances. These effects varied in severity but dramatically improved 20 days after the infusion, according to the researchers.
