Micrograph showing DLBCL

WASHINGTON, DC—Roughly half of patients who responded to chimeric antigen receptor (CAR) T-cell therapy in the ZUMA-1 trial have retained that response at a median follow-up exceeding 8 months.

The CAR T-cell therapy, axicabtagene ciloleucel (formerly KTE-C19), initially produced an objective response rate (ORR) of 82% in this trial of patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL).

At a median follow-up of 8.7 months, 44% of all patients (53% of responders) are still in response, and 39% are in complete response (CR).

Thirteen percent of patients had grade 3 or higher cytokine release syndrome (CRS), and 28% had neurologic events.

There were 2 deaths related to axicabtagene ciloleucel.

Frederick L. Locke, MD, of Moffitt Cancer Center in Tampa, Florida, presented these updated results from ZUMA-1 at the AACR Annual Meeting 2017 (abstract CT019).

ZUMA-1 is sponsored by Kite Pharma but is also funded, in part, by the Leukemia and Lymphoma Society Therapy Acceleration Program.

Patients and treatment

The trial enrolled 111 patients, 101 of whom were successfully treated with axicabtagene ciloleucel. Seven patients could not be treated due to serious adverse events, 1 due to unavailable product, and 2 due to non-measurable disease.

Seventy-seven of the patients had diffuse large B-cell lymphoma (DLBCL), and 24 had transformed follicular lymphoma (TFL) or primary mediastinal B-cell lymphoma (PMBCL). Eighty-five percent of patients had stage III/IV disease.

Seventy-nine percent were refractory to chemotherapy and did not have a prior autologous stem cell transplant (auto-SCT). Twenty-one percent did undergo auto-SCT and relapsed within 12 months of the procedure.

Sixty-nine percent of patients had received 3 or more lines of prior therapy, and 54% were refractory to 2 consecutive lines of prior therapy.

For this study, the patients received a conditioning regimen of cyclophosphamide (500 mg/m²) and fludarabine (30 mg/m²) for 3 days.

Two days after the conditioning regimen was completed, patients received axicabtagene ciloleucel at a target dose of 2 × 10⁶ CAR T cells/kg.

Efficacy

The following table shows overall response data, response data at 6 months, and ongoing responses at the primary analysis data cut-off.

	DLBCL (n=77)		TFL/PMBCL (n=24)		Combined (n=101)
	ORR (%)	CR (%)	ORR (%)	CR (%)	ORR (%)	CR (%)
ORR	82	49	83	71	82	54
Month 6	36	31	54	50	41	36
Ongoing	36	31	67	63	44	39

The researchers said the ORR was generally consistent in key subgroups. The ORR was 83% in patients who were refractory to their second or greater line of therapy and 76% in patients who relapsed within 12 months of auto-SCT.

Overall, the median duration of response was 8.2 months. However, the median duration of response has not been reached for patients with a CR.

At a median follow-up of 8.7 months, the median overall survival has not been reached.

Safety

The most common grade 3 or higher adverse events included anemia (43%), neutropenia (39%), decreased neutrophil count (32%), febrile neutropenia (31%), decreased white blood cell count (29%), thrombocytopenia (24%), encephalopathy (21%), and decreased lymphocyte count (20%).

The incidence of grade 3 or higher CRS was 13%, and the incidence of neurologic events was 28%. These represent decreases from the interim analysis of ZUMA-1, when the rate of grade 3+ CRS was 18%, and the rate of neurological events was 34%.

“We believe the rates of CRS and neurologic events decreased over the course of the study as clinicians gained experience in the management of adverse events,” said Jeff Wiezorek, MD, senior vice-president of clinical development at Kite Pharma.

There were 3 deaths throughout the course of the trial that were not a result of disease progression.

Two deaths were deemed related to axicabtagene ciloleucel. One was a case of hemophagocytic lymphohistiocytosis. The other was cardiac arrest in the setting of CRS.

The third death was the result of a pulmonary embolism and was considered unrelated to axicabtagene ciloleucel.

Half of patients retain response to CAR T-cell therapy