Durable response after tisagenlecleucel in adults with relapsed/refractory follicular lymphoma: ELARA trial update

• DOI: 10.1182/blood.2023021567
• Publication Date: 2024-01-09T22:15:56Z
• Authors: Martin Dreyling; Nathan Hale Fowler; Michael Dickinson; Joaquin Martinez-...; Arne Kolstad; Jason Butler; Monalisa Ghosh; Leslie Popplewell; Julio C. Chavez; Emmanuel Bachy; Koji Kato; Hideo Harigae; Marie José Kersten; Charalambos Andre...; Peter A. Riedell; P. Joy Ho; José Antonio Pére...; Andy I. Chen; Loretta J. Nastoupil; Bastian von Tresckow; Andrés José María...; Takanori Teshima; Piers E. M. Patten; Joseph P. McGuirk; Andreas L. Petzer; Fritz Offner; Andreas Viardot; Pier Luigi Zinzani; Ram Malladi; Ines Paule; Aiesha Zia; Rakesh Awasthi; Xia Han; Davide Germano; Darragh O’Donovan; Roberto Ramos; Harald J. Maier; Aisha Masood; Catherine Thieble...; Stephen J. Schuster
• Keywords: RISK; 0301 basic medicine; IL-6; tisagenlecleucel, relapsed/refractory follicular lymphoma, ELARA trial; Clinical Trials and Observations; [SDV]Life Sciences [q-bio]; Medizin; 610; Biology and Life Sciences; 600; PHASE-2; OPEN-LABEL; RELAPSE; METABOLIC TUMOR VOLUME; 03 medical and health sciences; CELLS; Medicine and Health Sciences; NON-HODGKIN-LYMPHOMA

Abstract 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.