TY - JOUR
T1 - Durable response after tisagenlecleucel in adults with relapsed/refractory follicular lymphoma
T2 - ELARA trial update
AU - Dreyling, Martin
AU - Fowler, Nathan Hale
AU - Dickinson, Michael
AU - Martinez-Lopez, Joaquin
AU - Kolstad, Arne
AU - Butler, Jason
AU - Ghosh, Monalisa
AU - Popplewell, Leslie
AU - Chavez, Julio C.
AU - Bachy, Emmanuel
AU - Kato, Koji
AU - Harigae, Hideo
AU - Kersten, Marie José
AU - Andreadis, Charalambos
AU - Riedell, Peter A.
AU - Ho, P. Joy
AU - Pérez-Simón, José Antonio
AU - Chen, Andy I.
AU - Nastoupil, Loretta J.
AU - von Tresckow, Bastian
AU - María Ferreri, Andrés José
AU - Teshima, Takanori
AU - Patten, Piers E.M.
AU - McGuirk, Joseph P.
AU - Petzer, Andreas L.
AU - Offner, Fritz
AU - Viardot, Andreas
AU - Zinzani, Pier Luigi
AU - Malladi, Ram
AU - Paule, Ines
AU - Zia, Aiesha
AU - Awasthi, Rakesh
AU - Han, Xia
AU - Germano, Davide
AU - O'Donovan, Darragh
AU - Ramos, Roberto
AU - Maier, Harald J.
AU - Masood, Aisha
AU - Thieblemont, Catherine
AU - Schuster, Stephen J.
N1 - Publisher Copyright:
© 2024 American Society of Hematology
PY - 2024/4/25
Y1 - 2024/4/25
N2 - Tisagenlecleucel is approved for adults with relapsed/refractory (r/r) follicular lymphoma (FL) in the third- or later-line setting. The primary analysis (median follow-up, 17 months) of the phase 2 ELARA trial reported high response rates and excellent safety profile in patients with extensively pretreated r/r FL. Here, we report longer-term efficacy, safety, pharmacokinetic, and exploratory biomarker analyses after median follow-up of 29 months (interquartile range, 22.2-37.7). As of 29 March 2022, 97 patients with r/r FL (grades 1-3A) received tisagenlecleucel infusion (0.6 × 108-6 × 108 chimeric antigen receptor–positive viable T cells). Bridging chemotherapy was allowed. Baseline clinical factors, tumor microenvironment, blood soluble factors, and circulating blood cells were correlated with clinical response. Cellular kinetics were assessed by quantitative polymerase chain reaction. Median progression-free survival (PFS), duration of response (DOR), and overall survival (OS) were not reached. Estimated 24-month PFS, DOR, and OS rates in all patients were 57.4% (95% confidence interval [CI], 46.2-67), 66.4% (95% CI, 54.3-76), and 87.7% (95% CI, 78.3-93.2), respectively. Complete response rate and overall response rate were 68.1% (95% CI, 57.7-77.3) and 86.2% (95% CI, 77.5-92.4), respectively. No new safety signals or treatment-related deaths were reported. Low levels of tumor-infiltrating LAG3+CD3+ exhausted T cells and higher baseline levels of naïve CD8+ T cells were associated with improved outcomes. Tisagenlecleucel continued to demonstrate highly durable efficacy and a favorable safety profile in this extended follow-up of 29 months in patients with r/r FL enrolled in ELARA. This trial was registered at www.clinicaltrials.gov as #NCT03568461.
AB - Tisagenlecleucel is approved for adults with relapsed/refractory (r/r) follicular lymphoma (FL) in the third- or later-line setting. The primary analysis (median follow-up, 17 months) of the phase 2 ELARA trial reported high response rates and excellent safety profile in patients with extensively pretreated r/r FL. Here, we report longer-term efficacy, safety, pharmacokinetic, and exploratory biomarker analyses after median follow-up of 29 months (interquartile range, 22.2-37.7). As of 29 March 2022, 97 patients with r/r FL (grades 1-3A) received tisagenlecleucel infusion (0.6 × 108-6 × 108 chimeric antigen receptor–positive viable T cells). Bridging chemotherapy was allowed. Baseline clinical factors, tumor microenvironment, blood soluble factors, and circulating blood cells were correlated with clinical response. Cellular kinetics were assessed by quantitative polymerase chain reaction. Median progression-free survival (PFS), duration of response (DOR), and overall survival (OS) were not reached. Estimated 24-month PFS, DOR, and OS rates in all patients were 57.4% (95% confidence interval [CI], 46.2-67), 66.4% (95% CI, 54.3-76), and 87.7% (95% CI, 78.3-93.2), respectively. Complete response rate and overall response rate were 68.1% (95% CI, 57.7-77.3) and 86.2% (95% CI, 77.5-92.4), respectively. No new safety signals or treatment-related deaths were reported. Low levels of tumor-infiltrating LAG3+CD3+ exhausted T cells and higher baseline levels of naïve CD8+ T cells were associated with improved outcomes. Tisagenlecleucel continued to demonstrate highly durable efficacy and a favorable safety profile in this extended follow-up of 29 months in patients with r/r FL enrolled in ELARA. This trial was registered at www.clinicaltrials.gov as #NCT03568461.
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U2 - 10.1182/blood.2023021567
DO - 10.1182/blood.2023021567
M3 - Article
C2 - 38194692
AN - SCOPUS:85185816749
SN - 0006-4971
VL - 143
SP - 1713
EP - 1725
JO - Blood
JF - Blood
IS - 17
ER -