TY - JOUR
T1 - Axicabtagene ciloleucel in the non-trial setting
T2 - Outcomes and correlates of response, resistance, and toxicity
AU - Jacobson, Caron A.
AU - Hunter, Bradley D.
AU - Redd, Robert
AU - Rodig, Scott J.
AU - Chen, Pei Hsuan
AU - Wright, Kyle
AU - Lipschitz, Mikel
AU - Ritz, Jerome
AU - Kamihara, Yusuke
AU - Armand, Philippe
AU - Nikiforow, Sarah
AU - Rogalski, Michael
AU - Maakaron, Joseph
AU - Jaglowski, Samantha
AU - Maus, Marcela V.
AU - Chen, Yi Bin
AU - Abramson, Jeremy S.
AU - Kline, Justin
AU - Budde, Elizabeth
AU - Herrera, Alex
AU - Mei, Matthew
AU - Cohen, Jonathon B.
AU - Smith, Stephen D.
AU - Maloney, David G.
AU - Gopal, Ajay K.
AU - Frigault, Matthew J.
AU - Acharya, Utkarsh H.
N1 - Publisher Copyright:
Copyright © 2020 American Society of Clinical Oncology. All rights reserved.
PY - 2020/9/20
Y1 - 2020/9/20
N2 - PURPOSE Axicabtagene ciloleucel (axi-cel) was approved by the Food and Drug Administration for relapsed aggressive B-cell non-Hodgkin lymphoma in part on the basis of durable remission rates of approximately 40% in a clinical trial population. Whether this efficacy, and the rates of toxicity, would be consistent in a postcommercial setting, with relaxed eligibility criteria and bridging therapy, is unknown. This study describes the efficacy and safety correlates and outcomes in this setting. PATIENTS AND METHODS One hundred twenty-two patients from 7 medical centers in the United States were treated with axi-cel and were included in a modified intent-to-treat (mITT) analysis. Seventy-six patients (62%) were ineligible for the ZUMA-1 trial. Response and toxicity rates, duration of response (DOR), survival, and covariates are described on the basis of the mITT population. Correlative studies on blood and tumor samples were performed to investigate potential biomarkers of response and resistance. RESULTS Median follow-up was 10.4 months. In the mITT population, the best overall and complete response (CR) rates were 70% and 50%, respectively. Median DOR and progression-free survival (PFS) were 11.0 and 4.5 months in all patients and were not reached (NR) in CR patients. Median overall survival (OS) was NR; 1-year OS was 67% (95% CI, 59% to 77%). Although response rates were similar in the ZUMA-1-eligible and ZUMA- 1-ineligible groups (70% v 68%), there was a statistically significant improvement in CR rate (63% v 42%, P = .016), DOR (median, NR v 5.0 months; P = .014), PFS (median, NR v 3.3 months; P = .020), and OS (1-year OS, 89% v 54%; P,.001) in patients who were ZUMA-1 eligible. Rates of grade$3 cytokine release syndrome and neurotoxicty were 16% and 35%, respectively. CONCLUSION Axi-cel yields similar rates of overall response and toxicity in commercial and trial settings, although CR rates and DOR were more favorable in patients eligible for ZUMA-1.
AB - PURPOSE Axicabtagene ciloleucel (axi-cel) was approved by the Food and Drug Administration for relapsed aggressive B-cell non-Hodgkin lymphoma in part on the basis of durable remission rates of approximately 40% in a clinical trial population. Whether this efficacy, and the rates of toxicity, would be consistent in a postcommercial setting, with relaxed eligibility criteria and bridging therapy, is unknown. This study describes the efficacy and safety correlates and outcomes in this setting. PATIENTS AND METHODS One hundred twenty-two patients from 7 medical centers in the United States were treated with axi-cel and were included in a modified intent-to-treat (mITT) analysis. Seventy-six patients (62%) were ineligible for the ZUMA-1 trial. Response and toxicity rates, duration of response (DOR), survival, and covariates are described on the basis of the mITT population. Correlative studies on blood and tumor samples were performed to investigate potential biomarkers of response and resistance. RESULTS Median follow-up was 10.4 months. In the mITT population, the best overall and complete response (CR) rates were 70% and 50%, respectively. Median DOR and progression-free survival (PFS) were 11.0 and 4.5 months in all patients and were not reached (NR) in CR patients. Median overall survival (OS) was NR; 1-year OS was 67% (95% CI, 59% to 77%). Although response rates were similar in the ZUMA-1-eligible and ZUMA- 1-ineligible groups (70% v 68%), there was a statistically significant improvement in CR rate (63% v 42%, P = .016), DOR (median, NR v 5.0 months; P = .014), PFS (median, NR v 3.3 months; P = .020), and OS (1-year OS, 89% v 54%; P,.001) in patients who were ZUMA-1 eligible. Rates of grade$3 cytokine release syndrome and neurotoxicty were 16% and 35%, respectively. CONCLUSION Axi-cel yields similar rates of overall response and toxicity in commercial and trial settings, although CR rates and DOR were more favorable in patients eligible for ZUMA-1.
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U2 - 10.1200/JCO.19.02103
DO - 10.1200/JCO.19.02103
M3 - Article
C2 - 32667831
AN - SCOPUS:85091191289
SN - 0732-183X
VL - 38
SP - 3095
EP - 3106
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 27
ER -