Point of Care Significance 7/10

ELARA Update: Tisagenlecleucel Shows Durable Responses at 29 Months in Relapsed Follicular Lymphoma

Extended follow-up of the phase 2 ELARA trial in 97 patients with relapsed/refractory follicular lymphoma showed a 68% complete response rate and estimated 24-month PFS of 57%. Median PFS, duration of response, and overall survival were not reached. Low levels of tumour-infiltrating LAG3+CD3+ exhausted T cells and higher baseline naive CD8+ T cells were associated with better outcomes, highlighting potential biomarkers for patient selection.

The original study

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

Authors
Dreyling M, Fowler NH, Dickinson M, Martinez-Lopez J, Kolstad A, Butler J, et al.
Journal
Blood
Type
Journal Article, Research Support, Non-U.S. Gov't, Clinical Trial, Phase II, Multicenter Study
PMID
38194692
Read the original study →

Original 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.