In a retrospective study reported by Nastoupil et al in the Journal of Clinical Oncology, researchers in the U.S. Lymphoma CAR T Consortium described outcomes with standard-of-care use of the autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel in patients with relapsed or refractory large B-cell lymphoma, including overall and complete response rates similar to those observed in the registrational phase II ZUMA-1 trial. Results from ZUMA-1 showed overall and complete response rates of 83% and 58% in this setting.
“The safety and efficacy of axicabtagene ciloleucel in the standard-of-care setting in patients with relapsed/refractory large B-cell lymphoma was comparable to the registrational ZUMA-1 trial.”— Nastoupil et al
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Study Details
The study involved data from all patients with relapsed/refractory large B-cell lymphoma who underwent leukapheresis as of September 2018 at 17 U.S. institutions with the intent to receive standard of care axicabtagene ciloleucel.
Key Findings
Of 298 patients who underwent leukapheresis, 275 (92%) received infusion of axicabtagene ciloleucel. Overall, 129 of these patients (43% of all patients, 47% of those receiving axicabtagene ciloleucel) would not have met ZUMA-1 eligibility criteria due to presence of comorbidities at the time of leukapheresis.
Among patients receiving axicabtagene ciloleucel infusion, grade ≥ 3 cytokine release syndrome occurred in 7% (any grade in 91%) and grade ≥ 3 neurotoxicity occurred in 31% (any grade in 69%), with all cases of neurotoxicity resolving except for fatal cerebral edema in one patient. Overall, 62% of patients received a dose or more of tocilizumab; 55% received glucocorticoids for cytokine release syndrome, neurologic events, or both; 33% were transferred to the intensive care unit; and 7% required vasopressors, 7% required intubation/mechanical ventilation, and 3% required dialysis. Nonrelapse-related mortality was 4.4% (n = 12), with causes consisting of infection in eight patients, axicabtagene ciloleucel–related toxicity in two (hemophagocytic lymphohistiocytosis in one patient and cerebral edema in the other), and unknown causes not attributable to lymphoma in two.
By comparison, in ZUMA-1, grade ≥ 3 cytokine release syndrome occurred in 11% of patients, grade ≥ 3 neurotoxicity occurred in 32%, and nonrelapse mortality was 3.7%.
Best overall and complete response rates were 82% and 64%, respectively. At a median follow-up of 12.9 months from the time of infusion, median progression-free survival was 8.3 months (95% confidence interval = 6.0–15.1 months) and median overall survival was not reached, with estimated 12-month rates of 47% and 68%, respectively.
On multivariate analysis, factors associated with poorer progression-free survival and overall survival included lactate dehydrogenase before conditioning chemotherapy > upper limit of normal (hazard ratio [HR] = 1.9, P = .001; HR = 3.0, P = .0001) and Eastern Cooperative Oncology Group performance status of 2 to 4 vs 0/1 (HR = 1.7, P = .010; HR = 1.8, P = .020).
The investigators concluded: “The safety and efficacy of axicabtagene ciloleucel in the standard-of-care setting in patients with relapsed/refractory large B-cell lymphoma was comparable to the registrational ZUMA-1 trial.”
Frederick L. Locke, MD, of the Moffitt Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by grants from the National Institutes of Health and National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.
