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ZUMA-1: Anti-CD19 CAR T cells show clinical benefit in DLBCL
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SAN DIEGO — Three-quarters of patients with non-Hodgkin lymphoma responded to treatment with anti-CD19 chimeric antigen receptor T cells, according to findings presented during the late-breaking abstract session of the ASH Annual Meeting and Exposition.
“Outcomes in refractory DLBCL have been extremely poor,” Sattva S. Neelapu, MD, deputy department chair ad interim in the department of lymphoma/myeloma at The University of Texas MD Anderson Cancer Center, said during his presentation. “There is clearly an unmet need for these patients.”
Neelapu presented interim data on a cohort of 111 patients with diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (TFL) and primary mediastinal B-cell lymphoma (PMBCL).
Approximately half of the cohort was aged 60 years or older (median age, 58 years; range, 25-76; 73% men). The median number of prior therapies was three (range 1-12), and 77% of the cohort had refractory disease.
Patients received a target dose of 2 × 106 anti-CD19 CAR T cells/kg (KTE-C19, Kite Pharma) after a low-dose conditioning regimen of 500 mg/m2 cyclophosphamide and 30 mg/m2 fludarabine daily for 3 days.
Objective response rate served as the primary endpoint. Researchers also observed duration of response, frequency of adverse events and levels of CAR T cells and serum cytokines.
The current dataset included 93 patients with at least 1 month of follow-up data available and 50 patients with at least 3 months of follow-up.
“The majority of the patients on the study were treated, with 101 of 111 receiving a target dose of KTE-C19,” Neelapu said.
At 1 month, the ORR was 71%, and complete response rate was 38%. Among patients with at least 3 months of follow-up data, the ORR was 76% and the complete response rate was 52% (P < .0001).
At the 3-month assessment, the complete response rate was 39%. Seven patients with stable disease or partial response at 1 month converted to a complete response at 3 months.
“The treatment effect was consistent across all key covariates,” Neelapu said, noting effect regardless of CD19 H-score, CD4/CD8 ratio and other parameters.
Grade three or worse adverse events occurred in 92% of the cohort, which included grade three or higher cytokine release syndrome in 13%. Neurologic events of grade three or higher occurred in 29% of patients. There were no cases of cerebral edema.
Grade five events were reported in 3% of the cohort. Two were deemed to be related to KTE-C19, whereas the other was unrelated.
The most frequently reported adverse events were neutropenia (63%) and anemia (42%).
Further analysis indicated that peak CAR T-cell expansion occurred between days 7 and 14.
“We observed an increase in a number of cytokines and chemokines,” Neelapu said, noting that Il-6 and IL-15 levels were significantly increased.
“The ZUMA-1 study met the primary endpoint,” Neelapu concluded. “There was a six-fold higher complete response rate compared with historical outcomes.”
Adverse events were managed effectively across the 22 study sites, most of which had no previous CAR T-cell experience, Neelapu said.
“These results are comparable to previous KTE-C19 studies,” he said. —by Rob Volansky
Reference :
Neelapu S, et al. Abstract LBA-6. Presented at: The ASH Annual Meeting and Exposition; Dec. 3-6, 2016; San Diego.
Disclosures: Neelapu reports board of directors or advisory committee roles with and research funding from Kite Pharma. Please see the abstract for a list of all other researchers’ relevant financial disclosures.